Some of the information below concerning Faculty Mentors, interests and contact information is out of date. This information is being updated continuously. (Last updated 20 October 2010)


Barry W Ache, Ph.D., Distinguished Professor, Director, Center for Smell and Taste; PhD, Physiology, University of California Santa Barbara, 1970

Primary Department: Zoology, CLAS
Secondary Department: Neuroscience, COM

My research program, which is located at both the Whitney Laboratory and the McKnight Brain Institute, is directed at understanding the cellular mechanisms of chemosensory transduction, especially the interaction of the cyclic nucleotide and phosphoinositide signaling pathways and the functional implication of multiple signaling pathways on odor coding. My research uses both marine invertebrate and mammalian animal models. In addition, I also direct the Center for Smell and Taste, which fosters and integrates chemical senses research and training at the University of Florida.

Contact: bwa@whitney.ufl.edu


Barbara-Anne Battelle, Ph.D., Biology, Syracuse University, 1972

Primary Department: Whitney Laboratory/Neuroscience, COM
Secondary Department: Biochemistry,

We study the modulation of retinal functions by signals from circadian clocks. We are particularly interested in understanding the biochemical mechanisms underlying the regulation of the photoresponse by circadian clocks. The effects of clock input on photoreceptors is being examined at several levels – gene expression, post-translational modification of proteins, and changes in structure. A current focus is to examine the function of a class III unconventional myosin that is found in photoreceptors of both vertebrates and invertrates. As with most unconventional myosins, the functions of this protein is unknown. It is, however, it a major clock-regulated phosphoprotein in some species and critical for photoreceptor function. We anticipate these studies will lead to a more complete understanding of photoreceptor function and of the causes of retinal degenerations.

Contact: battelle@whitney.ufl.edu


Stephen J Blackband, PhD, Nottingham University, England, 1985

Primary Department: Neuroscience, COM

Engaged in the development and application of Magnetic Resonance Imaging (MRI) and spectroscopy (MRS). Primary research studies include:

  1. development and application of MR microscopy. Primary applications are to single neural cell microimaging and studies of isolated perfused brain slices. The long term goal is to elucidate the origins of MR signals in tissues. Collaborating in the development of a web based MR mouse brain atlas.
  2. development of high magnetic field MR techniques and technology. This includes novel volume and phased array radiofreqeuncy coil designs, and their application on our high field instrumentation.
  3. development of diffusion tensor imaging and applications in animal and human studies.

blackie@mbi.ufl.edu/p>


Jennifer Bizon, Ph.D. Neurobiology and Behavior, University of California, Irvine, 1998

Primary Department: Neuroscience, COM
Secondary Department:> Psychiatry, COM

Age-related cognitive decline is a substantial problem, particularly as expectations of longevity have increased two-fold in the last century, and it is estimated that upwards of 25% of people over age 65 exhibit some form of cognitive deficit. As such, there is great interest in:

  1. early detection of failing cognition;
  2. determining neurobiological factors responsible for such decline; and
  3. developing effective treatments to slow or even reverse cognitive decline in aging.

Research in my laboratory addresses all three of these issues using animal models of age-related changes in learning, memory, and executive functions (e.g. – decision-making), both in “normal” (non-pathological) aging and in models of Alzheimer’s disease. Specific projects include development of novel and sensitive behavioral assays for early detection of cognitive deficits, quantitative neuroanatomical studies of the brain to determine how changes in specific neuron populations are related to cognitive deficits in aging, and testing of novel pharmacological agents for treating such deficits.

Contact: jennifer.bizon@mbi.ufl.edu


David C Bloom, Ph.D. Vanderbilt University, 1990

Primary Department: Molecular Genetics & Microbiology, COM

A major focus of my lab is the development of Herpes Simplex Virus (HSV) as a vector for expressing peptides in the nervous system. The natural neurotropism of HSV and its ability to be transported trans-synaptically make it a useful tool for studying the nervous system. Currently, our studies are focused in three main areas:

  1. use of herpes vectors to express Fragile X Mental Retardation Protein (FMRP) in FMR1 knock-out mice to study the role of FMRP in Fragile X Disease,
  2. testing a novel neurovirulence mutant of HSV for its efficacy in promoting regression of malignant glioblastoma in mouse and rat models, and
  3. use of HSV as a neuroanatomic tracer to study the circuitry of the eye-blink reflex.

Contact:dbloom@ufl.edu


Donald C Bolser, PhD, Physiology, Univ of South Florida, 1985

Cough is the most common reason why sick patients visit physicians in this country. This reflex also is the most common manifestation of pulmonary disease. Ironically, relatively little is known about this important phenomenon. Over the last eight years my research efforts have focused on identifying new drugs that inhibit cough by actions inside the central nervous system. Recent work has identified a common mode of action of a wide variety of centrally-acting antitussive drugs. The results suggest that centrally-active antitussive drugs inhibit cough at a common site of action. Results from these studies will expand our understanding of the mechanism(s) of action of antitussive drugs and the regulation of the central reflex pathway for cough. Studies in my laboratory are investigating the role of muscles of the upper chest, such as the pectoralis major, in the production of cough. These muscles are important because they stabilize the chest wall during cough. Furthermore, in patients with spinal injuries, upper chest muscles can be important in maintaining an effective cough reflex. For example, the pectoralis major muscle can compensate for loss of abdominal muscle function in spinally-injured patients and allow effective cough to be produced. We have found in animal models of cough that the pectoralis major muscle is controlled in a behavior-specific manner. That is, its pattern of activation can shift from inspiratory to expiratory during different respiratory defensive reflexes. This pattern of activation differs greatly from that of the diaphragm (the primary inspiratory muscle) and abdominal muscles (expiratory) which have stereotypical response patterns during inspiratory or expiratory respiratory defensive reflexes. Ultimately, these studies will lead to a greater understanding of the compensatory mechanisms that occur in pulmonary defensive reflexes following spinal injury.

Contact: bolserd@mail.vetmed.ufl.edu


David R Borchelt, PhD, Univ. of Kentucky, 1986

Primary Department: Neuroscience, COM

Over the past several years there has been tremendous progress in identifying the genes that, when mutated, cause a number of neurodegenerative disorders, including familial Alzheimer’s disease, familial amyotrophic lateral sclerosis, and Huntington’s disease. These disorders are all progressive, fatal disorders that result from the dysfunction and death of specific populations of nerve cells. In all of these disorders, a change in the amino acid sequence of specific proteins initiates a cascade of events that lead to disease. My laboratory has been committed to investigations designed to elucidate the molecular processes by which specific mutant proteins cause disease. This work involves the use of transgenic mouse models, in which the introduction of mutant human genes elicits a disorder that resembles the human disease, as well as cell culture systems to examine the effect of mutations on the function and biology of the mutated proteins. Collectively , these approaches provide insight into the molecular mechanisms of disease and have the potential to identify new therapeutic strategies for these disorder.

Contact: borchelt@mbi.ufl.edu


Margaret M Bradley, Ph.D., Psychology, University of Wisconsin-Madison,

Primary Department: Psychology, CLAS
Secondary Department: Clinical & Health Psychology, CHP

Using different brain mapping techniques (e.g., functional magnetic resonance imaging, dense electrode EEG), we are investigating the neural mechanisms underlying affective and attentional processing in people with and without diagnosable anxiety disorders. Drawing on an animal model of motivation, we are mapping the subcortical and cortical neural circuits involved in emotional perception and imagery. In addition to neural mapping, we measure autonomic and somatic indices of affective and attentional mobilization, using cardiovascular, electrodermal, electromyographic and respiratory measures. Taken together, our research is consistent with the hypothesis that affective cues activate basic motivational circuits that have evolved to mediate appetitive and defensive behaviors.

Contact: bradley@ufl.edu


Adrie W Bruijnzeel, PhD, Neuropharmacology, Utrecht University, 2001

Primary Department: Psychiatry, COM

My research focuses on investigating the neuronal substrates that underlie acute and protracted nicotine and opioid withdrawal. We attempt to reverse the affective signs of drug withdrawal by modulating neuropeptide levels in the entire brain, the central nucleus of the amygdala and the bed nucleus of the stria terminals We study the affective signs of nicotine withdrawal by using the intracranial self-stimulation (ICSS) procedure. This entails the implantation of electrodes in the medial forebrain bundle of rats and subsequently training the rats on the ICSS procedure. The acute administration of drugs of abuse lowers brain reward thresholds (i.e. potentiates brain reward function), while precipitated and spontaneous drug withdrawal results in an elevation of brain reward thresholds (i.e. deficit in brain reward function). In addition, we are investigating the long-term effects of exposure to low doses of nicotine and anesthetics in the air. We hypothesize that chronic repeated exposure to low doses of drugs of abuse induces adaptations in brain reward systems and brain stress systems which renders individuals more sensitive for the development of a chemical dependency.

Contact: awbruijn@ufl.edu


Paul R Carney, MD, University of Valparaiso, 1990

Primary Department: Pediatrics, COM

Dr. Carney’s primary focus of research is to develop an on-line, real-time Automated Seizure Warning and Prevention System for use by epileptic patients and their caregivers. His scientific work also involves genetic and neurophysiologic analysis of seizures in animal models and children. This program conducts bench-to-bedside research focusing on Brain Dynamics and Epilepsy. The Partnership brings together a multi-disciplinary group of research scientists who are pioneers in the areas of signal processing, optimization, hybrid VLSI and DSP, computation neurophysiology, neuroanatomy, epilepsy, and neurosurgery.

Contact: carnepr@peds.ufl.edu


Brian Y Cooper, PhD, Biopsychology, Univ of Iowa, 1980

Primary Department: Oral Surgery, COD

Our laboratory examines the properties pain receptors or nociceptors. Nociceptors have evolved a variety of capacities to detect and transduce mechanical, thermal and chemical events. They also express paracrine agents that they release into tissue or into the synaptic cleft as co-transmitters. Our laboratory has developed techniques that permit detailed examination of the discrete phenotypes of nociceptors and how they express different combinationsof properties that reflect their tissue dependent functional specializations. Our focus has been mainly on heat, protons, ATP, opioid, eicosanoid and cholinergic mechanisms.

bcooper@dental.ufl.edu


Jesse Dallery, Ph.D., Associate Professor

Primary department: Psychology

Choice, Substance Abuse, Impulsivity, Relapse, Cigarette Smoking
The goals of my research program are to connect basic behavior analysis with clinically relevant phenomena, and conduct studies within each domain. Using animal laboratory preparations, we’re examining some of the fundamental environmental variables and behavioral processes that regulate behavior, including drug abuse, impulsive behavior, and relapse. We use quantitative models of choice as one lens through which to view and understand these complex phenomena. Some questions: How does chronic nicotine administration affect choice? What are some behavioral risk factors that increase the liability to drug effects? In a complementary research track, we’re applying the principles and processes studied in the animal lab to understand analogous behavior (drug abuse, cigarette smoking, impulsive behavior, relapse) in humans. Cigarette smoking, the largest preventable factor leading to morbidity and mortality in developed countries, is an important and practical target for inquiry and intervention. We’re developing several models to understand the dynamics of choice for cigarettes, including a behavioral model of impulsive choice. The laboratory models may be enormously useful for initial testing of both pharmacological and behavioral interventions designed for relapse prevention. Also, these models could further our understanding about whether and how critical variables (e.g., cue exposure, contextual factors, nicotine deprivation, drugs of abuse, pharmacotherapies, stress, etc) affect the impulsive choices that lead to or prevent relapse.

Contact: dallery@ufl.edu


Paul W. Davenport, Ph.D., Professor,

Primary department: Physiological Sciences:

Research in my laboratory combines invasive studies on animals with non-invasive human experiments to develop an understanding of the role of the cerebral cortex in respiratory sensations and the control of breathing. The transduction properties of respiratory muscle afferents are under investigation with the correlation of muscle mechanics with afferent discharge. The central projections of these afferents are studied electrophysiologically by recording thalamic and cortical neurons that are activated by respiratory muscle afferents. Cortical evoked potentials elicited by loads to breathing and psychophysical measures are used as a tool for studying respiratory sensation in humans. Respiratory load sensation is studied in adults, children and asthmatic patients. Psychophysical and evoked potential studies are being used with asthmatic patients that have difficulty sensing their asthmatic attack. The combination of the animal and human studies allows for identification of the neural mechanisms of respiratory load sensation and the related adjustments to breathing mediated by the cerebral cortex.

Trainee Participation in this Research: Students learn respiratory and neurophysiological methods including lung volume, airflow and pressure recording in humans and experimental animals for tracheostomy, arterial and venous cauterization, exposure of respiratory muscles, spinal laminectomy and craniotomy must be mastered. Electrophysiological techniques are used for recording single unit activity form peripheral nerves, dorsal rootlet recording, extracellular microelectrodes recordings in the central nervous system, brain surface electrode recording and muscle electromyography, In humans, skin electrodes are used for recording brain evoked potentials and muscle activity. Psychophysical methods are used in human studies of respiratory sensation. The physiological parameters recorded in these studies are processed by appropriate computer analysis.

Contact: DavenportP@mail.vetmed.ufl.edu


Thomas B DeMarse, Ph.D., Learning and Memory, Purdue University, 1997

Primary Department: Biomedical Engineering, COEG

My research interfaces living rat cortical cells cultured in vitro to a computer to study neural computation, processing, and coding. Rat cortical neurons are cultured on a 60 channel multi-electrode array that can stimulate and record from neurons among a small population of about 25,000 cells. These neurons are interfaced to a robotic body via computer interface that acts as an artificial body. With this system we can manipulate many variables of interest (e.g., different patterns of sensory/stimulation inputs) and measure changes in the network’s activity in real-time. Combined with optical imaging, this system represents a powerful platform to study how cortical neural networks process, learn and encode information.

Contact: tdemarse@bme.ufl.edu


Darragh P Devine, Ph.D., Psychology, Concordia University, Montreal, 1993

Primary Department: Psychology, CLAS

Research in my laboratory is currently focused on two major projects. One project deals with analysis of the physiological and behavioral consequences of acute and chronic stress exposure. We are currently examining the neurobiology of stress using highly emotional (as opposed to physiological) stressors, as we believe that this approach models the type of stress exposure that humans routinely experience. Human emotional stress exposure appears to be very important in the onset and maintenance of a variety of psychopathological conditions. Accordingly we are examining individual differences in vulnerability to stress-induced psychopathology, neuroadaptations that occur during chronic stress exposure, and the specific neurotransmitter systems and hormonal systems that participate in stress-induced psychopathology. We coordinate all our studies with examinations of behavioral concomitants of the stress exposure, and we focus largely on evaluation of anxiety-related behaviors. The other major focus of my laboratory is the neurobiological basis of self-injurious behavior. Self-injury is a devastating behavioral disturbance that is expressed by individuals with autism, Lesch-Nyhan syndrome, intellectual handicaps, and other conditions. The disorder is poorly understood at present. We have identified specific variables that confer increased or diminished vulnerability to self-injury, and we are examining the neurobiological concomitants of this vulnerability to self-injure. In each of these research endeavors, we combine a variety of behavioral, cellular and molecular analyses to uncover the neurological basis of the observed responses.

Contact: dpdevine@ufl.edu


Roger B Fillingim, Ph.D., Psychology, University of Alabama at Birmingham, 1990

Primary Department: Operative Dentistry, COD

The major emphasis in our laboratory is human psychophysical research on sex differences in pain responses. We use a variety of laboratory pain procedures, such as cutaneous heat, pressure pain, ischemic pain and cold pressor pain. A large body of work now indicates that experimental pain responses differ for women and men, with women typically exhibiting lower thresholds and tolerances and higher magnitude estimates of suprathreshold pain. In addition, we have demonstrated greater temporal summation of thermal pain among women. We have also reported on several biological and psychosocial factors that appear to influence experimental pain differently in women and men, including sex hormones, blood pressure, family history, pain coping and anxiety. We are also examining sex differences in responses to the opioid analgesics morphine and pentazocine. Several studies suggest that women show greater analgesic responses to “kappa-like” drugs, including pentazocine, nalbuphine and butorphanol. Recent work also indicates that morphine may produce greater analgesia in women. Interestingly, the rodent literature generally suggests the opposite. Thus, we are examining analgesic responses to morphine and pentazocine using three experimental pain models, and we are also evaluating menstrual cycle effects on these responses. Another interest in our laboratory is sex-related influences on clinical pain. In this regard, we have examined psychophysical responses in patients with pain conditions such as temporomandibular disorder (TMD), interstitial cystitis, and fibromyalgia, all of which are more prevalent in women than men. A relatively new area of investigation involves ethnic differences in pain responses. We will be starting a new study of responses to multiple experimental pain procedures in three different ethnic groups: African Americans, Hispanic Americans and non-Hispanic whites. We will explore perceptual, cardiovascular and neuroendocrine responses to pain in these three groups.

Contact: rfilling@ufl.edu


Thomas C Foster, Ph.D., Bowman Gray School of Medicine, 1987

Primary Department: Neuroscience, COM

My research has focused on understanding brain mechanisms for modifying synaptic transmission and their relationship to memory, particularly in the context of cognitive decline during aging. Synaptic plasticity is thought to mediate the associative and information storage properties of neurons, and intracellular calcium (Ca2+) levels occupy a pivotal position in regulating synaptic plasticity, determining whether synaptic strength increases or decreases in response to neuronal activation. Interestingly, synaptic plasticity processes change over the lifespan and thus could underlie cognitive changes with advanced age. Currently I am the principal investigator on two active grants that support work examining the mechanisms for memory changes during aging. Research funded by NIA characterized several biological markers of age-related memory impairment and provides a model linking age-related memory decline and a major hypothesis for aging, altered Ca2+ homeostasis, through a change in Ca2+ signaling cascades to markers of brain aging including the shift in synaptic plasticity, increased susceptibility to neural toxicity, and altered gene regulation. Our current research is directed at examining the role of various sources of Ca2+ regulation in mediating age-related changes and testing the effectiveness of treatments in ameliorating memory decline and preventing/reversing markers of brain aging. I am also funded through NIMH to study estrogen effects on hippocampal function across the lifespan. Interestingly, many of the effects of estrogen are diametrically opposite to changes observed in aged memory impaired animals. Our work indicates that estrogen rapidly increases cell excitability and the strength of synaptic transmission. Importantly, our work suggests that there is a reduced responsiveness of estrogen signaling pathways with advanced age. Our future research in this area is directed at examining age-relate changes in estrogen signaling in the hippocampus at the behavioral, physiological, biochemical, and genomic levels. As part of this work we employ genetically altered mice and we have initiated a number of studies using molecular techniques (gene microarrys, RT-PCR, in situ hybridization). In summary, my research program utilizes a combination of behavioral characterization with biochemical, molecular, and electrophysiological techniques to obtain a vertically integrated perspective on neural aging, from the molecular to the cognitive level.

Contact: foster@mbi.ufl.edu


Charles J. Frazier, Ph.D., University of Colorado, 1997

Primary Department: Pharmacodynamics, COP

Research in my laboratory is focused on identifying the specific neurophysiological mechanisms through which cholinergic afferents projecting from the medial septum to the hippocampus contribute to the regulation of hippocampal excitability. At a cellular level, we study the functional expression of both muscarinic and nicotinic acetylcholine receptors in an attempt to determine how activation and/or desensitization of these receptors can modulate the intrinsic behavior of hippocampal neurons. However, we are also interested in mechanisms through which activation of cholinergic receptors can modulate the behavior of both small groups of neurons (such as interneuron / principal neuron pairs), and larger systems of neurons that are capable of generating coordinated activity. This research is motivated by the fact that the septohippocampal cholinergic projection has been strongly linked to information processing and memory formation, as well as to highly characteristic patterns of neuronal activity such as gamma and theta rhythms. Degradation of this pathway has been clearly implicated in senile dementia and Alzheimer’s disease, and may play a role in other disorders that involve tight control of hippocampal excitability. We approach these questions using in vitro preparations of rat brain slices in combination with differential interference contrast microscopy, fluorescent imaging, photometry, and multiple techniques of electrophysiology.

Contact: cjfraz@ufl.edu


Jianbo Gao, Ph.D., Electrical Engineering, UCLA, 2000

Primary Department: Electrical & Computer Engineering, COM

Broadly interested in developing novel linear and nonlinear

Linda F. Hayward, Asst Professor,
BA, Psychobiology, Univ. of California at Santa Cruz, 1980
MS, Kinesiology, Univ. of Washington, 1984
PHD, Physiology, Northwestern Univ., 1990

Primary Department: Physiological Sciences, CVM

Four types of signals have been studied: EEG data for seizure prediction/detection; fMRI data; Neuron firing data; Pathological tremor data (including essential tremor and tremor in the Parkinson’s disease). Novel methods developed include chaos theory based methods (recurrence time statistics; logarithmic displacement curves, etc.) and random fractal theory based (mono- and multi-fractal).

Contact: gao@ece.ufl.edu


Leslie J Gonzalez Rothi, Ph.D., University of Florida, 1978

Primary Department: Neurology, COM

Dr Gonzalez Rothi has centered her research in two main arenas:

  1. the cognitive neuropsychology of human communication as well as skilled, purposive, limb movement planning and performance, and
  2. cortical plasticity in the mature CNS associated with new learning, functional recovery after CNS damage or injury, and response to rehabilitation.

Currently she is funded by both NIDCD/NIH and the VA Rehabilitation Research and Development Service with clinical trials in treatment of aphasia, alexia, limb apraxia and aprosodia, the effects of adjunctive drug therapies in association with the previously listed treatment trials, and functional neuroimaging of functional recovery resulting from rehabilitation; health services research including the development of a brief cognitive inventory for use in prediction of treatment candidacy as well as functional outcome, development of a quality of life measure to be used in the context of aphasia after stroke; a large scale study of the interaction of language attributes in the context of aphasia, the impact of social factors such as race and marital status on outcome in aphasia, and the impact of intensity of treatment on outcome in aphasia.

Contact: gonzalj@neurology.ufl.edu


Linda F. Hayward, Ph.D., Physiology, Northwestern Univ., 1990

Primary Department: Physiological Sciences, CVM

The primary focus of my research is to understand how central neural circuits interact to control blood pressure, heart rate and respiration. Currently my lab is investigating the role of specific regions in the pons (parabrachial nucleus) and midbrain (periaqueductal gray region) and the neurotransmitters important to these regions in descending control of sympathetic and parasympathetic drive in both the normal and the hypertensive animal. We utilize a combined approach of electrophysiology, neuroanatomy, immunohistochemistry and neuropharmacology to define the role of specific brain nuclei in autonomic control and to understand how this role changes in disease states. We are also interested in investigating the interaction between cardiovascular control and respriatory control and how specific nuclei and neurotransmitters modulate both systems either simultaneously or independently.

Contact: lindah@ufl.edu


Jeffrey K. Harrison, Ph.D.

Primary department: Pharmacology

Our laboratory is interested in the molecular characterization of G-protein coupled receptors. Collectively these receptors form a large superfamily of genes whose encoded proteins are characterized structurally as having seven stretches of hydrophobic amino acids that are capable of spanning the plasma membrane. Functionally, they mediate the actions of a wide variety of hormones, neurotransmitters, and drugs. Our research is focused primarily on receptors for chemokine (chemoattractant cytokine) peptides. We use a variety of experimental approaches with the goal to understand the location of expression and cellular signaling mechanisms of these receptors. Techniques in the lab include pharmacological, biochemical, immunological, and molecular biological methodologies. Most of our attention is focused on determining the functional role of chemokines and their receptors in the central nervous system. Chemokines are a class of pro-inflammatory peptides that are important mediators of leukocyte migration. We have identified a number of chemokine receptors in the rat and have determined that the central nervous system expresses many of these genes. Chemokine receptors are being studied in transfected mammalian cells, primary cultured cells derived from rat brain (i.e. microglia, astrocytes, and neurons), as well as a number of neuroimmunological

Contact: harrison@pharmacology.ufl.edu


Marieta B. Heaton, Ph.D., NC State University, 1971

Primary Department: Neuroscience, COM

Our laboratory is investigating mechanisms underlying the fetal alcohol syndrome, a condition characterized by devastating central nervous system damage in children, following exposure to alcohol in utero. For these studies, we are examining neuroanatomical changes resulting from developmental alcohol exposure, and the molecular mechanisms underlying these changes. We hypothesis that one such mechanism contributing to developmental alcohol neurotoxicity is an alcohol-mediated alteration in the expression of vital neurotrophic factors (NTFs) and/or their receptors. Alcohol also has well-defined effects on the cellular redox state, enhancing generation of destructive reactive oxygen species (ROS) and decreasing expression or activities of endogenous antioxidants. We therefore further hypothesize that alterations in NTF availability impact significantly on the cellular capacity to accommodate alcohol-induced ROS, since NTFs normally regulate the cellular redox state, by enhancing expression of antioxidants, and inhibiting ROS production, while increased ROS per se can lead to reductions in NTF expression through downregulation of NTF transcription. We propose that an additional mechanism critical to developmental alcohol neurotoxicity is the modulation of expression of cell death and survival genes. Experiments underway are investigating intracellular events, such as alcohol-mediated alterations in NTF signal transduction, which may underlie alcohol influences on each of these interacting processes. We are further investigating the possibility of amelioration of these destructive ethanol effects by application of exogenous antioxidants. Techniques being used include quantitative neuroanatomical analyses, immunohistochemistry, primary neuronal cell culture, neuronal survival assays, reactive oxygen species and antioxidant assays, and Western blot and ELISA protein quantification. These studies have the potential to elucidate important inter-related intracellular mechanisms underlying the devastating CNS damage seen in the fetal alcohol syndrome, and may suggest possible therapeutic strategies for ameliorating this damage.

Contact: heaton@mbi.ufl.edu


Dena R. Howland, Ph.D.

Primary Department: Neuroscience

The overall focus of the laboratory is to determine how the spinal cord responds to injury and what interventions may be used to enhance recovery based upon both anatomical and behavioral criteria. A variety of lesion models in both the rat and cat are being used. Our studies have shown that grafts of embryonic spinal cord can promote recovery following spinal cord injury in both developing and adult systems. These grafts can survive for long periods and undergo substantial differentiation. Although grafts into adult and developing systems both integrate with the host tissue, the grafts integrate more extensively and promote greater axonal growth when placed into the developing host system. This structural response difference is correlated with differences in behavioral recovery. We are continuing to assess the potential for grafts of embryonic spinal cord to enhance behavioral recovery and promote anatomical repair in the adult and believe that the mechanisms by which transplants may work in the adult versus developing system are different. A variety of neuroanatomical and molecular methods are being used to assess the cellular and axonal interactions that occur between the host and graft. The behavioral analysis focuses on several characteristics of locomotion including weight support, balance, interlimb coordination and angular kinematics. We are also currently studying the expression of several molecules that are know to affect axonal growth during development. These molecules include both growth-promoting and repulsive molecules as well as their putative receptors (e.g. netrin, proteoglycans, aggrecan, dcc). The differential display of these molecules in the adult and following injury may suggest mechanisms that affect growth which are present or absent in the developing versus adult versus injured systems. These differences may also suggest potential therapeutic strategies for the adult. To this end, we are degrading proteins as well as introducing genes to make proteins within the injured central nervous system. In addition to repair strategies using cellular and molecular approaches, we are also evaluating the effects of rehabilitation training paradigms on recovery in experimental animal models. These studies should begin to indicate whether training is important, whether the type of training is critical and whether training can be beneficial, detrimental or benign based upon behavioral and anatomical criteria.

Contact: howland@mbi.ufl.edu


Richard D Johnson, PhD., University of California, 1985

Primary Department: Physiological Sciences, CVM

In vivo and in vitro electrophysiology, neuroanatomy, and immunohistochemistry of the single sensory neurons, spinal cord and brainstem interneurons, and motoneurons mediating control of the reproductive and pelvic visceral organs; normal mechanisms, role in reproductive behavior and micturition, sensory and motor dysfunction following chronic spinal cord injury, chronic pain, efficacy of neural transplantation in recovery of function. Electrophysiology, neuroanatomy, and immunohistochemistry of the peripheral nerves with respect to chronic nerve injury and nerve regeneration; response properties of primary afferent receptors in skin, viscera, muscle, and efficacy of target-specific nerve trophic factors in recovery of function.

Contact: johnson@mbi.ufl.edu


Michael J Katovich, Ph.D., Physiology, University of California at Davis, 1976

Primary Department: Pharmacodynamics, COP

My lab focuses on six main research areas, which include: alterations in the renin-angiotensin system in hypertension and diabetes, temperature regulation, vascular reactivity, menopause,opiate dependency, and thirst. To study these areas, we utilize a combination of gene therapy approaches and classical physiological methods.

Contact: katovich@cop.ufl.edu


Maureen Keller-Wood, Ph.D., Univ. California, San Francisco, 1982

Primary Department: Pharmacodynamics, COP

My overall research interest is the physiologic adaptations to pregnancy. The laboratory is focusing on changes related to cortisol effects at the two receptors at which adrenal steroids (such as cortisol) bind: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). These receptors mediate physiologic effects necessary for regulating blood glucose, blood pressure, fluid and electrolyte excretion, appetite, and mood. In the brain and pituitary, these receptors are also critical for the proper regulation of adrenal secretion through feedback effects. In particular, we are interested in the role of these receptors in two inter-related adaptations of pregnancy: changes in regulation of the blood pressure and fluid balance, and the changes in feedback control of the hypothalamo-pituitary-adrenal (HPA) axis which allow a chronic increase in ACTH and cortisol levels during pregnancy. One of these projects has a major neuroscience component. In this project we are testing the hypothesis that during pregnancy progesterone antagonizes cortisol action at mineralocorticoid receptors (MR) in the hippocampus, which in turn reduces the feedback effect of cortisol and allows ACTH (and therefore cortisol) to chronically increase. We are looking at both physiologic changes in HPA function, changes in MR and GR pharmacology, and changes in corticosteroid-regulated genes and proteins in hippocampus, such as serotonin receptors. The model systems we use are pregnant and progesterone-treated ewes, and hippocampal cell cultures. We are also beginning a study to examine the ontogeny of MR and GR expression and action in the late gestation fetus. Although GR-related actions are known to be crucial for normal lung and GI development at the time of birth, we are interested in whether MR-mediated actions precede this and cause induction of genes important for maturation in the fetus. Among the sites we are interested in studying are the brainstem and the hippocampus. It is known that estrogen and progesterone exert developmental effects on neurons, in particular hippocampal neurons, and may also help “mature” pathways important for responses to cardiovascular “stress.” In these experiments we will look at the ontogeny of MR and GR in brainstem and hippocampus, as well as the induction of putative MR-induced genes, such as sgk and sodium channels.

Contact: kellerwd@cop.ufl.edu


Jeffrey A. Kleim, Ph.D., University of Illinois, 1997

Primary department: Neuroscience (COM) — and VA Medical center

The brain is a highly dynamic organ that is capable of structural and functional reorganization in response to a variety of manipulations. This neural plasticity is the mechanism by which the brain encodes experience. My laboratory examines how plasticity within rat and human motor cortex supports learning in the intact brain and “relearning” after stroke. We use intracortical microstimulation in rats and transcranial magnetic stimulation in humans to examine how motor training alters the functional organization of motor cortex. This work has demonstrated that rehabilitation-dependent recovery of motor function after stroke is associated with a reorganization of movement representations in rodent motor cortex. Furthermore, there are specific behavioral and neural signals that drive both recovery and plasticity. These experiments are being used to test novel therapies for enhancing motor recovery in stroke patients.

Contact: jkleim@ufl.edu


Eric D Laywell, Ph.D., Anatomy & Neurobiology, University of Tennessee, 1993

Primary Department: Neuroscience, COM

My research aims are:

  1. identification and cultivation of multipotent neural stem/progenitor cells from a variety of brain tissues;>
  2. transplantation of stem/progenitor cell to test engraftability and integration within both normal and injured brain areas;
  3. exploration of the potential for transdifferentiation of non-neural stem cells (i.e. hematopoietic and hepatic); and
  4. analysis of subventricular zone anatomy and cytoarchitecture.

Contact: elaywell@mbi.ufl.edu


Mark H. Lewis, Ph.D., Vanderbilt University, 1980

Primary Department: Psychiatry, COM

The research interests of this lab involve clinical and animal model studies of autism and related neurodevelopmental disorders. Specifically we are focused on the abnormal repetitive behavior (e.g., stereotyped behavior, compulsions, rituals, insistence on sameness) characteristic of children and adults with autism and related neurodevelopmental disorders. In our clinical studies, we are examining how restricted, repetitive behaviors in autism are related to deficits in motor control (control of involuntary and voluntary movements), and cognitive flexibility (behavioral inhibition, set shifting, exploration). In our animal studies, we are investigating the neurobiology underlying the development and expression of abnormal repetitive behavior in a mouse model. One research direction involves examining the brain changes associated with the prevention of abnormal repetitive behavior by early experience. Other work in the lab is focused on using pharmacological and biochemical methods to identify the neural circuitry mediating abnormal repetitive behavior in these animals.

Trainees working on projects related to our animal model will be able to learn a variety of techniques relevant to the neurobiological basis of behavior. These include, but are not limited to, stereotaxic surgical techniques, automated and observational behavioral assessment, pharmacological methods, and biochemical methods (e.g., immunoassay and histochemical techniques) to examine brain changes.

Contact: mlewis@psychiatry.ufl.edu


James Liao, Ph.D.

Primary Department: Whitney Marine Laboratory

Our lab is interested in the biomechanical and neural mechanisms of how animals interact with their environment. We use fishes as our experimental model because they provide several strong advantages. First, they makeup over half of all living vertebrates, thus providing access to enormous morphological and behavioral diversity. Second, they are the most basal vertebrates, so their organ systems are relatively simple and accessible compared to more derived vertebrates, such a mammals. Third, advances in zebrafish genetics allow us to use powerful in vivo techniques to monitor individual and population-level neuronal morphology and activity. Fourth, most larvae are transparent, enabling direct observation of cell-to-cell connectivity and activity, as well as behavioral studies involving ablation of specific neurons.

Our research seeks to uncover the mechanisms of ecologically relevant behaviors through the lens of biomechanics, engineering, neurobiology, physiology and evolution. Our philosophy is to ask questions from a sound understanding of the natural history of the organism, choose laboratory techniques to test questions in the most direct manner possible, and then see if our findings explain our observations of behavior in the natural environment.

Our lab has three current research topics.

  1. Fish swimming in turbulence
    We are interested in the mechanics, energetics and control of locomotor behaviors in natural flow conditions. Fishes routinely encounter turbulence in nature, such as when swimming behind a rock in a stream or when schooling. Turbulence is characterized by vortical flows that span a wide range of sizes and strengths and is difficult to study because of its chaotic nature. To simplify this task, our approach is to expose fish to the well-characterized, turbulent wakes of geometric objects in which we can systematically alter vortex size, spacing, and shedding frequency. We have found that under certain conditions swimming fish can exploit experimentally-generated vortices to decrease muscle activity. Current and future work expands upon our earlier work featured on the cover of Science and focuses on the mechanisms of vortex association in different fish species behind cylinders, flags and foils as well as exploring the material flexibility of the body that enables environmental vortex recapture.
  2. Function and organization of the lateral line
    Animals must accurately sense their environment in order to translate them into appropriate motor behaviors. Hair cells convert mechanical deflections into electrical signals to initiate a complex sensory pathway that provides the foundation for several sensory modalities in vertebrates, such as hearing and balance. In fishes, hair cells of the lateral line system enable the ability to sense water flow, or “distance touch,” which is critical to predator evasion and prey capture. Afferent neurons directly contact hair cells and provide the first site of signal processing. Rapid progress has been made in understanding hair cell function, yet we still know relatively little about how information is subsequently processed by afferent neurons. Our lab takes advantage of optical, genetic and electrophysiological techniques to examine neuronal morphology, connectivity and activity in intact, behaving zebrafish. Our work explores the functional organization of lateral line afferent neurons with the ultimate goal of understanding how the ability to sense hydrodynamic signals can influence swimming performance.
  3. Field studies of natural behavior
    How do fishes behave in their natural environment? We are using our laboratory studies to make predictions about behaviors in the field. One exciting and applied aspect of this approach is the ability to contribute to issues in stream restoration and fish passageway. How do you design an optimum stream or fish ladder? Can the biomechanical and sensory limitations of organisms predict the behavioral ecology of species? This work allows us to ground truth our laboratory findings in an ecological context and provides inspiration for new projects.

Contact: jiao@whitney.ufl.edu

Website: https://www.whitney.ufl.edu/people/current-research-faculty/james-c-liao-phd/


Yijun Liu, Ph.D., University of Texas, 1999

Primary Department: Psychiatry, COM

The research interest in this lab, located at the University of Florida McKnight Brain Institute, is to develop neuroimaging methods for both basic neuroscience study and clinical investigation. In particular, we use functional magnetic resonance imaging (fMRI) to model neural-system circuits mediating various brain functions and disorders.

Current work includes:

  1. Using fMRI to probe the neuropathological and neuropharmacological bases of certain psychiatric disorders, such as affective disorders (e.g., Obsessive-Compulsive Disorder), Autism/Abnormal Repetitive Behavior, Schizophrenia, etc., and their treatment;
  2. Development of in vivo neural-system modeling methods to explore the role of subcortical structures (e.g., the thalamus, basal ganglia, midbrain, and cerebellum) in the perceptual and adaptive processes underlying human cognition and affection, and especially, in the maintenance of our (self-) consciousness;
  3. Development of approaches to the real timing of neural-hormonal interaction, e.g., an fMRI model of hypothalamic function in the control of feeding behavior and use these approaches to study obesity, diabetes, drinking and gambling problems, and eating disorders (including substance abuse) in humans; and
  4. A Dynamic Brain Mapping (DBM) program using the real-time fMRI techniques, with integration of recent development in MR phase imaging, perfusion imaging, and diffusion imaging.

Contact: yijunliu@ufl.edu

Laboratory Website: http://fmri.mbi.ufl.edu


Ron Mandel, Ph.D., University of Southern Cal., 1986

Primary Department: Neuroscience, COM

Gene transfer for the study of neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, Canavan disease, Leigh syndrome, and stroke. Trainees are welcome to participate in all phases of the laboratory which include stereotaxic surgery, behavioral testing, histology, immunocytochemistry, and some molecular techniques

Contact: rmandel@ufl.edu


Thomas H Mareci, Ph.D., University of Oxford, 1982

Primary Department: Biochemistry and Molecular Biology, COM

Our research program uses nuclear magnetic resonance (NMR) techniques to study fundamental questions of tissue structure and biochemical processes in living systems. We examine excised tissue with MR microscopy and spectroscopy; extending these measurements to studies in vivo. We develop unique NMR measurement and processing methods, and custom hardware/software systems for our studies of cellular and molecular processes. Our current projects are the following:

  1. Study blood-spinal-cord barrier and blood-brain barrier disruption, using dynamic contrast enhanced MR imaging in vivo, following trauma. As part of this study, we are modeling the kinetics of lesion enhancement in a longitudinal study of barrier disruption over weeks;
  2. Use diffusion tensor imaging to map fiber tracts in highly structured white matter and gray matter of nervous tissue. Using this method, we are mapping the fiber structure of the brain and spinal cord following trauma;
  3. Design unique RF coils for implantation to enhancement sensitivity. These implanted coils are inductively coupled to an external coil during measurements and provide a gain up to a factor of 4 in signal-to-noise ratio. Because of the gains possible, these coils allow the acquisition of very high spatial resolution MR images and spectra.

Contact: thmareci@ufl.edu


Michael Marsiske, Ph.D., Pennsylvania State University, 1992

Primary Department: Clinical and Health Psychology, CHP

  1. Older adults’ everyday problem solving abilities, their relationship to basic cognitive and intellectual performance and to functional competence, and the role of social partners in cognitive collaboration
  2. the range of modifiability (plasticity) in adults’ intellectual functioning, with a particular recent focus on intraindividual variability and inconsistency in elders’ cognitive performance, and
  3. antecedents (especially sensorimotor) of individual differences in adult cognitive and intellectual functioning. Much of this research focuses on the interdependency of postural control (balance) and complex cognition in later life.

Contact: marsiske@ufl.edu


Ed Meyer, Ph.D., MIT, 1978

Primary Department: Pharmacology, COM

My research group develop models for age-related neuropathological disorders and novel treatment approaches for these disorders as well.Some models and treatments are based on somatic gene transfer, others on more classical anatomical, cellular, and pharmacological approaches. Work in the lab extends from molecular biology and virology (generating new AAV derived vector systems for gene transfer into brain) through behavior, with a significant amount of cell biology (including a new project with embryonic stem cells) thrown in.

Contact: meyerlab@grove.ufl.edu


Drake Morgan, Ph.D., UNC Chapel Hill 1998

Primary Department: Psychiatry, COM

There are several lines of research being investigated in Dr. Morgan’s laboratory. We are still developing models of addiction in rats and trying to identify predictors and consequences of this behavior. Behavioral studies include drug self-administration, drug discrimination, schedule-controlled behavior, “impulsivity” and other operant testing, and locomotor activity. There is a continuing interest in opioids and cocaine, which may branch off towards other drugs of abuse, including MDMA, methamphetamine, nicotine, THC, and alcohol. Additional areas of research include the examination of changes in the sensitivity to pain and opioids as a function of aging.

Contact: DrakeM@psychiatry.ufl.edu


David F Muir, Ph.D., City Univ of NY, Mount Sinai Med Center, 1987

My research examines peripheral nerve and spinal cord regeneration with the intent to develop therapies for improved functional recovery after traumatic injury. A second effort investigates peripheral nerve sheath tumors and mechanisms of tumorigenesis. Our work in neuronal regeneration has focused on two main issues:

  1. discovering the fundamental mechanisms by which nervous system regeneration is regulated and
  2. developing technologies to remove inhibitors of nervous system regeneration to improve recovery of function after injury.

Our inceptive studies in peripheral nerve injury models show that neuronal regeneration can be inhibited by a class of extracellular molecules called chondroitin sulfate proteoglycans (CSPG). We discovered that peripheral nerve injury induces the expression of extracellular matrix-degrading enzymes that degrade and inactivate inhibitory CSPG. Our work indicates that CSPG-degrading enzymes can markedly improve the regeneration of transected nerve in animal models and suggests a low risk adjunctive therapy to improve the outcome of conventional nerve repair surgery. This approach has also been applied to a major clinical challenge to enable the use of allogenic and xenogenic nerve grafts in the large number of patients with intractable nerve deficits. Related work in a spinal cord injury model gave promising evidence that inactivation of CSPG by enzymatic degradation can improve the growth promoting potential of the spinal cord as well. Investigating the therapeutic value of enzymes that degrade inhibitory CSPG have a great potential to overcome our present inability to prevent functional loss resulting from nervous system injury. My research in peripheral nerve sheath tumors centers on tumorigenesis in Neurofibromatosis type 1 (NF1). NF1 is a common autosomal dominant disease characterized by a high incidence of neurofibroma. My collaborative studies test the hypothesis that the Schwann cell is initially mutated and clonally expanded in neurofibromas. We have established numerous Schwann cell lines from neurofibromas and have documented numerous genetic alterations in these cells. We recently developed a working xenograft model for plexiform neurofibroma in mice with an NF1 background. Present aims focus on the mechanisms underlying neovascularization and vascular requirements in neurofibromas with the goal of testing the response of neurofibromas to anti-angiogenic therapies.\

Contact: muir@mbi.ufl.edu


Harry S. Nick, Ph.D., University of Pennsylvania, 1982

Primary Department: Neuroscience, COM

Our laboratory is interested in understanding the molecular mechanisms which control tissue specific gene regulation. Research has focused on proteins which exhibit both pro- and anti-inflammatory activities in the lung, intestine and brain. These genes include manganese superoxide dismutase (MnSOD), a potent cyto protective anti-oxidant protein, the inducible nitric oxide synthase (iNOS) gene which generates elevated levels of the powerful neurotransmitter and vasodilator, nitric oxide (NO) and cytoplasmic phospholipase A2 (cPLA2) which controls intracellular levels of arachidonate metabolites. These genes are also linked through transcriptional regulation by a subset of pro-inflammatory mediators, including bacterial endotoxin (LPS), interleukin 1 (IL-1), tumor necrosis factor (TNF-a) and interferon-g.

Contact: hnick@ufl.edu


Sara Jo Nixon

Primary department: Psychiatry, COM

The research interests of my lab focus on the neurocognitive consequences of severe drug abuse in humans, focusing on alcohol but including polydrug and other aspects.

Contact: sjnixon@psychiatry.ufl.edu


Lucia Notterpek, Ph.D., University of California Los Angeles, 1994

Primary Department: Neuroscience, COM

The overall interests of the laboratory are the cellular interactions of neurons and glia during the development of the nervous system and how these processes are altered in disease. A key element for neuronal functioning is myelination, the glial ensheathment of axonal processes that serves to facilitate signal propagation from the neuronal cell body to the synaptic terminal. A glial molecule termed peripheral myelin protein 22 (PMP22) has been shown to have key roles in normal nerve development, since point mutations, deletions or duplications of the PMP22 gene are associated with nerve degeneration and disease. It is the main goal of my laboratory to define the roles of PMP22 in the peripheral nervous system and in the pathogenesis of neuromuscular disorders.A major area of research is to elucidate how altered turnover rate and intracellular trafficking of mutated PMP22 contribute to the progressive subcellular pathogenesis of PMP22-associated demyelinating neuropathies. Recent data suggest that inhibition of the ubiquitin-proteasome pathway in Schwann cells leads to accumulation of the endogenous PMP22 in newly-defined ubiquitin-containing cytoplasmic inclusions, called aggresomes. Aggresomes are thought to form when proteasome activity gets saturated due to the expression of misfolded proteins. Furthermore, both overexpressed wild type and mutated PMP22s also aggregate in pericentriolar aggresomes. Three specific questions that arose from these findings are currently being addressed

  1. What is the role of the ubiquitin-proteasome pathway in the pathogenesis of peripheral neuropathies?
  2. What are the effects of aggresomes on Schwann cell biology?
  3. How does overexpression of, or point mutations in, the PMP22 gene affect the turnover rate of PMP22 (and of other myelin proteins) and in turn myelin stability?

Another major area of investigation is to define the role of PMP22 in Schwann cell biology. Studies indicate that PMP22 is a component of intercellular junctions in epithelial and endothelial cells, and shares significant homology with the claudin tight junction proteins. Utilizing molecular and biochemical tools, we are investigating whether PMP22 is a functional or structural component of intercellular junctions, first in epithelial and endothelial cells and then in myelinating Schwann cells. A goal of these studies is to establish a functional assay where we can evaluate the roles of PMP22 in normal cells and in the disease paradigms.

Contact: notterp@mbi.ufl.edu


Roger L Papke, Ph.D., Cornell University, 1987.

Primary Department: Pharmacology and Therapeutics, COM

We study neuronal nicotinic acetylcholine receptors (nAChR) in order to understand the role that these receptors play in the basic function of the brain. While the nerve cells of the brain are very complex, activated or inhibited by many different kinds of drugs, with specific drugs perhaps even having more than one kind of effect on a single cell, there are ways to study these nicotinic receptors that makes it easier to understand how nicotine and related drugs may be working in the brain. One way we do this is to utilize the genes for these nAChR which have been isolated and cloned. We make copies of the genes, in the form of RNA, to be injected into Frog oocytes. After a few days the oocytes can be stimulated by nicotinic drugs, the same way that a cell in the brain might be. Another approach we take is to study the natural occurring brain nicotine receptors, either in acutely dissociated neurons, or by recording from neurons in brain slices. By studying the neurons in brain slices we can determine how nicotinic drugs affect connections between cells, and also how treatments to the whole animal can affect circuits within the brain. We study drugs that either act like nicotine, or alternatively may block the effects of nicotine, either in vitro (with oocytes) or ex vivo (in brain slices). In this way we hope to learn the different effects these drugs may have in specific parts of the brain, including those known to be involved with learning and memory (e.g. the hippocampus) addictive behavior, or other brain function related to brain nAChR. A second major goal in the lab is to use the nAChR as general models for synaptic receptors of the type which directly couple drug binding to the generation of electrical currents. We are identifying parts of the molecule which are important in coupling the binding of neurotransmitters to the conformational change associated with the active form of the receptor. We study the roles that various parts of the receptor protein play in determining how the receptor functions by using recombinant DNA techniques to create new forms of the genes (mutants and chimeras) that will combine or exchange the properties of the different forms of the receptors. We study both the pharmacology and the biophysics of these artificial receptors. Some of the experiments make use of patch-clamp techniques to study the currents that flow through single molecules when they are activated by nicotine or other drugs.

Contact: rpapke@college.med.ufl.edu


Panos M Pardalos, Ph.D., University of Minnesota, 1985

Primary Department: Industrial and Systems Engineering, COEG

Epilepsy is among the most common disorders of the nervous system (second only to stroke). For the vast majority of patients, epileptic seizures occur in the absence of identifiable external precipitants. Thus, one needs to look into the characteristics of the epileptogenic brain itself to find an explanation for the intermittent occurrence of epileptic seizures. Given the complexity of brain circuitry and recent results, it is highly likely that the brain behaves in a nonlinear fashion. If this is the case, the dynamical features of the epileptic brain (especially the transition to epileptic seizures) may be explained by the theory of nonlinear chaotic systems. Measures derived from the theory of nonlinear dynamics and discrete optimization techniques are used for prediction of impending epileptic seizures from analysis of multielectrode electroencephalographic (EEG) data.

Contact: pardalos@ufl.edu


Joanna Peris, Ph.D., Oregon Health Sciences University, 1984

Primary Department: Pharmacodynamics, COP

The primary interest of my lab is understanding the neurochemical mechanisms of ethanol addiction. As part of this research, we measure how dopaminergic and amino acid neurotransmission in brain regions highly implicated in the alcohol addiction process (e.g., nucleus accumbens) are altered in rats exhibiting high degrees of ethanol self-administration. The combination of on-line capillary electrophoresis separation and laser-induced fluorescence detection with in vivo microdialysis in awake behaving animals provides a remarkable insight into the details and mechanisms of ethanol-induced changes in neurotransmission. In particular, the ability to measure second-to-second fluctuations in dopamine, taurine and other amino acids during periods of ethanol craving and subsequent self-administration will be important in helping delineate the neurochemical mechanisms underlying the addictive process vs that underlying actual alcohol intoxication. We induce rats to willingly and reliably self-administer ethanol without food or liquid deprivation.and then implant cannula into the relevant brain regions of the animals. So far, we have revealed some very novel findings about the time course of changes in taurine and dopamine in the first few minutes after both ethanol injections and self-administered ethanol in naïve and alcoholic rats. Related studies include determining the changes in both excitatory and inhibitory transmission that take place in hippocampus after chronic ethanol exposure that may account for decreases in long-term potentiation and memory decrements caused by such treatment.

Contact: peris@cop.ufl.edu


Mohan K Raizada, Ph.D., 1972, Distinguished Professor, Biomedical Science, Univ. of Kanpur, India

Primary Department: Physiology and Functional Genomics, COM

Project I

Our research group is currently active in the following three projects:

Project 1: Mechanisms of Neurogenic Hypertension: We have previously established that an intrinsic brain renin-angiotensin system (RAS) is critical in the control of cardiovascular (CV) functions and that its dysregulation results in hypertension and associated CV disease (CVD). Our research group is currently involved in the elucidation of the mechanism of this dysregulation in an attempt to identify novel therapeutic targets for control and treatment of neurogenic hypertension. The following studies are ongoing:

  1. A. We are testing the hypothesis that activation of microglial cells and release of cytokines in the cardioregulatory brain regions are key cellular events in the initiation of neurogenic hypertension.
  2. B. Studies are underway to demonstrate anatomical and functional neural system-bone marrow communication pathways relevant to the cardiovascular system. We are testing the hypothesis that cardiovascular related brain regions (i.e. PVN, RVLM, and NTS) regulate the release and function of bone marrow-derived stem cells (BMPCs). Impairment of this communication may compromise the BMPCs ability to repair hypertension-induced cardiovascular damage
  3. C. We are studying the involvement of newly discovered members of the RAS, angiotensin converting enzyme 2 (ACE2) and (pro)renin receptor (PRR), in neurogenic hypertension. Our approach uses in vivo gene transfer in the CV-brain regions to regulate the expression of ACE2 and PRR enabling us to determine altered outcomes in hypertension.

Project 2: Potential of ACE2-Angiotensin-(1-7) axis of the RAS as a target for the control of pulmonary hypertension (PH) and CVD: Our studies have shown that overexpression of ACE2 or Ang-(1-7) prevents and partially reverses PH in animal models. This observation has led us to hypothesize that pharmacological and genetic targeting of ACE2/Ang-(1-7) would be a novel strategy for the treatment of PH and other CVD. The following lines of investigation are ongoing in this area:

  1. A. Structure-based drug discovery approach has led us to identify small molecule ACE2 activators. We are studying whether these activators exert beneficial outcomes in PH, myocardial infarction-induced cardiac damage, and heart failure.
  2. B. We are investigating whether ACE2 activators can be used to produce beneficial outcomes in diabetes and hypertension-induced cardiac and renal damage.

Project 3: Genetically-modified stem cells for PH and CVD therapeutics: We are testing the hypothesis that BMPCs are dysfunctional in PH and CVD because of an altered ACE2/Ang-(1-7) axis of the RAS. Stem cells from both animal models and patients are being used to test this concept. We seek to answer the following questions:

A. Are BMPCs and EPCs dysfunctional in PH and CVD?

B. Would overexpression of ACE2/Ang-(1-7) ameliorate dysfunctional BMPCs?

C. Would genetically modified BMPCs be better than unaltered BMPC therapy for PH and CVD?

Contact: mraizada@phys.med.ufl.edu


Roger L. Reep, Ph.D., Michigan State University, 1978

Primary Department: Physiological Sciences, CVM

My research is focused on development of a rodent model for studying the neglect syndrome.

Neglect is a human neurological disorder characterized by a failure to report, respond, or orient to novel or meaningful stimuli presented to the side of the body opposite a brain lesion, and is not explainable by a primary sensory or motor deficit. Some manifestation of neglect is found in about 40% of all cases of right hemisphere brain damage, typically produced by stroke. Neglect most often involves damage to a neural network for directed attention which includes specific regions of the cerebral cortex, thalamus and striatum. This disorder is disabling to patients and their families and is extremely difficult to treat because neglect patients are often not concerned with or aware of their neurological status. There are no effective therapies for neglect, and if recovery occurs it is usually incomplete. Over the past 26 years, we and colleagues at Northern Illinois University have developed a rat model of neglect which demonstrates direct behavioral, anatomical, and pharmacological applicability to human neglect patients. The model has been used to examine the neural mechanisms that produce neglect and recovery. These studies have focused mainly on the medial agranular cortex and its striatal projection zone, the dorsocentral striatum. Our studies indicate that the dorsocentral striatum may be the crucial site for the mechanisms which underlie recovery. These regions are components of a neural network for directed attention analogous to that found in primates. My group is investigating the organization of connections among the cortical, striatal, and thalamic portions of this circuitry. Through use of multiple axonal tracers, we are identifying the various types of neurons that participate in this network, and the patterns by which they are connected.

Contact: reepr@ufl.edu

Website: https://www.vetmed.ufl.edu/about-the-college/faculty-directory/roger-reep/


Paul J Reier, Ph.D., Case-Western Reserve Univ., 1972

Primary Department: Neuroscience, COM

Research in this laboratory is directed at the cell biology of neurons and glia in the developing and injured peripheral and central nervous systems with emphasis on: mechanisms associated with neuronal outgrowth, axon-glial interactions during axonal elongation and myelinogenesis, PNS and CNS demyelination and remyelination, glial responses to neuronal injury, axon-glial interactions, and neural tissue transplantation; immunology of neural tissue transplantation, magnetic resonance imaging of neural tissue; neurophysiological and behavioral correlates of spinal cord injury and repair, neural tissue culture and isolation of stem/progenitor cells from the adult CNS; ex vivo and in vivo gene delivery directed at neuronal rescue and regeneration in the injured nervous system; neural stem cell transplantation in CNS injury and repair. The focus of all these interests is on translational (i.e., bench-to-bedside)neurobiology. This laboratory in collaboration with other colleagues at the University of Florida were the first in this country to carry out a small clinical trial investigating the safety and feasibility of fetal neural tissue transplantation in people with a certain complication of spinal cord injury. Current studies in the laboratory continue to investigate the use of cells (i.e., stem or stem-like cells) for repairing the injured spinal cord, and some studies also are moving towards the application of this therapeutic modality to stroke. In conjunction with transplantation, we also are testing the combined effects of other approaches including gene delivery, rehabilitation, and low-dose irradiation. Some of these studies have also opened unexpected gateways to investigations pertaining to amyotrophic lateral sclerosis (Lou Gehrig’s disease). Our overall goal is to find approaches that will optimally combine with native intrinsic repair processes (i.e., neuroplasticity) that can lead to improvement in function in spinal cord injury and other neurological disorders.

Contact: reier@mbi.ufl.edu


Michael E Robinson, Ph.D., Bowling Green State University, 1988

Primary Department: Clinical and Health Psychology, CHP

Recent work has been in the area of sex and gender role differences in pain perception. More broadly, my interests are in the contributions of social learning, negative affect, and personality factors in pain perception and in the interface between these factors and the ?first-order? biological contributions to pain perception. Most recently we have begun to use fMRI in the study of pain perception and placebo analgesia (with Nicholas Verne, Don Price, Richard Briggs, Bruce Crosson). My lab has also developed a number of clinically relevant pain stimulation protocols that combine laboratory psychophysics with clinically relevant stimulation. In addition to the research interests I have maintained an active practice of pain psychology and am clinically active in the pain clinics at UF.

Contact: merobin@ufl.edu


Steven N Roper, M.D., Neurosurgery, UCLA, 1992

Primary Department: Neurological Surgery, COM

Dr. Roper’s laboratory is centered on the cellular basis of epilepsy. He uses electrophysiology and in vitro brain slices as well as histological methods to accomplish this. He is trying to understand how in utero insults that alter normal cortical development affect subsequent brain function and propensity to develop epilepsy. Dr. Roper also studies electrophysiology of hippocampal neurons obtained from people who undergo surgical treatment for medically intractable epilepsy. He tries to understand how changes in this tissue can lead to seizures and memory impairment in these patients.

Contact: roper@neurosurgery.ufl.edu


Neil E Rowland, Ph.D., London University, 1974

Primary Department: Psychology, CLAS

Obesity and eating disorders: studies on the role of serotonin, endocannabinoids, and other neural systems in the control of food intake in rats and mice. We combine studies of food intake after either acute or chronic (to examine for tolerance) administration of select pharmacological agents with determination of regional brain activation, using Fos immunoreactivity as a primary marker. The relationship between suppression of intake and development of learned flavor avoidances is also under investigation, as is the use of flavor discriminations in this protocol as a model for study of cortical memory representations. Alcohol and tobacco abuse: We are examining the role of stress, and in particular early life stress on alcohol consumption in adulthood in mice. In collaboration with Dr Kem (UF Pharmacology) we are testing the effect of novel nicotinic antagonists agents as potential anti-smoking agents, using a paradigm in which rats are trained to discriminate nicotine from placebo, and are investigating the role of conditioned cues in self-administration.

Neuroeconomics: we are beginning to investigate the neural basis of simple decision-making in rodents subjected to different schedules and/or choices of reinforcement.

Contact: nrowland@ufl.edu


Susan L Semple-Rowland, Ph.D., University of Florida, 1986

Primary Department: Neuroscience, COM

Our research program is focused on the development of molecular-based therapies for the treatment of inherited retinal diseases, development of regulatable gene expression systems for use in viral vector gene therapy, and identification and analyses of gene promoters that restrict gene expression to photoreceptor cells. We are currently in the midst of a very exciting time with regard to the use of gene therapies for curing blindness. Clinical trials are well underway that should pave the way for treatment of a myriad of inherited photoreceptor diseases in the next decade.

We specifically study Leber congenital amaurosis –type 1 (LCA1), a disease that causes blindness in newborn infants. Our avian model has the same biochemical defect as that in humans diagnosed with LCA1. We have characterized the genetic mutation underlying the biochemical defect and reversed blindness in these animals using gene therapy. Our current efforts are directed toward developing a therapy that provides life-long restoration of sight in these animals. Students in my laboratory employ molecular, biochemical, histological, and behavioral techniques to address this problem.

Contact: rowland@ufl.edu

Lab Website: http://www.mbi.ufl.edu/~rowland/

Department Website: http://neuroscience.ufl.edu/faculty-and-staff-directory/faculty/susan-semple-rowland-ph-d/

Barry Setlow, Ph.D., Neurobiology and Behavior, University of California, Irvine, 1998

Primary Department: Psychiatry, COM

Secondary Department: Neuroscience, COM

The overarching goal of research in my laboratory is to understand cost-benefit decision-making (decision-making in which one must weigh both the costs and benefits of various options), both under conditions of normal operation and in pathological conditions, such as addiction and attention deficit-hyperactivity disorder (ADHD), in which decision-making is altered. I use animal models in my research to investigate behavioral and neurobiological factors that influence decision-making under these conditions. Some specific projects in the laboratory involve neural mechanisms underlying the long-term effects of cocaine use on decision-making, relationships between adolescent decision-making and drug use, neural mechanisms of risky decision-making, and transgenic mouse models of ADHD.

Keywords: decision-making, addiction, impulsivity, risk-taking, animals, drugs, cognition

Contact: setlow@ufl.edu


W. Clay Smith, Ph.D., Yale University, 1990

Primary Department: Ophthalmology, COM

The research in my lab centers on the molecules involved in phototransduction– the biochemical process by which photons are converted into a neural signal. The phototransduction enzyme cascade is an exquisitely sensitive system, being capable of producing a neural response to a single photon. This responsiveness is due largely to two aspects of the cascade. First, the cascade is amplified at each protein-protein interaction step producing (or hydrolyzing, as the case may be) literally millions of final effector molecules per second. Secondly, the inactivation of the cascade is tightly regulated at each amplification point such that the enzyme system is quickly quenched and returned to the responsive state. This tightly regulated system is a wonderful model system from which to study the visual process and also use as a model system for other G-protein-coupled receptor systems. One of the many exciting things about phototransduction is that much of the process is conserved across ALL animals that have eyes, from the slimy flatworms to the crunchy insects and right on up to humans. This means that we can use whatever organism is best suited for our studies to approach a particular question regarding the visual cycle. Our lab currently has experiments ongoing with humans, mice, rats, rabbits, frogs, alligators (we are at the University of Florida afterall), ants, and horseshoe crabs. The general consensus is that if it can walk through our lab door or crawl across the benchtop it may well end up in our experiments. Our fundamental approach is a combination of molecular biology coupled with biochemistry and transgenic animal models. We do a lot of cloning work directed towards isolating components of the phototransduction system. From there it’s on to site-directed mutagenesis and heterologous expression systems to produce enough protein to determine out how the components interact. These interactions then direct us towards transgenic models, introducing altered components into the visual cascade in vivo to provide the ultimate verification of our results.

Contact: csmith@eye1.eye.ufl.edu


David W Smith, Ph.D., The University of Michigan, 1986

Primary Department: Psychology, CLAS; UF Center for Smell and Taste

Secondary Department: Otolaryngology-Head and Neck Surgery

Our laboratories are actively involved in studies of both hearing and smell. Current research projects in our auditory laboratories are concerned with the peripheral physiological and neural mechanisms underlying simple perceptual phenomena. These interests can be sub-divided into studies of the role of the descending, or olivocochlear efferent, neural system in normal, acoustic perception and perception resulting from electrical activation of the auditory system through a cochlear implant, or bionic ear. The efferent system descends from several areas of the mammalian brainstem to synapse on and influence the response of the outer hair cell receptors of the cochlea. Our work, using psychophysical and physiological measures in human and non-human listeners, characterizes the influence of this system on the perception of transient signals in noise and on selective auditory attention. Our research with the cochlear implant seeks to characterize the effects of electrode design, electrode contact placement, contact configuration and neural survival on psychophysical and physiological measures of implant performance in non-human subjects.
Our olfactory laboratory is concerned with studies of olfactory sensory neuron transduction mechanisms. We are particularly interested in investigations of the neural mechanisms underlying odor adaptation and masking. The laboratory employs operant behavioral techniques to characterize olfactory perception in genetically manipulated mice and in human subjects.

Contact: dwsmith@ufl.edu

Website: Smithlab


Wolfgang J Streit, Ph.D., Medical University of South Carolina, 1985

Primary Department: Neuroscience, COM

Dr. Streit’s work has resulted in the following basic contributions to science: 1) Development of a histochemical procedure for staining microglial cells; 2) Development of a novel biological concept of ‘Functional plasticity of microglia’; 3) Extensive immunophenotypical characterization of activated microglia and perivascular macrophages; 4) Re-evaluation of the brain as an ‘immunologically privileged organ’ and concomitant development of the idea that microglia make up the brain’s endogenous immune system. These ideas have taken a foothold in neurobiology and they are widely accepted today. What is important for the future are the ramifications of these fundamental biological principles for understanding and treatment of neurological dysfunction and disease. In other words, what is the functional significance of reactive microgliosis. Dr. Streit has been a strong proponent of the idea that reactive microgliosis occurs in response to neuronal injury and/or dysfunction. He has endorsed the idea that neuron-derived signals trigger and regulate microglial activation and that it is neuron-microglia interactions that are essential for ensuring proper brain function, both physiologically and pathologically. Throughout his scientific career, he has promoted the philosophy that reactive microgliosis is a beneficial process that reflects the ability of the CNS to cope with the sequelae of injury and to maximize post-injury regeneration efforts. This point of view, which stands in contrast to the idea that microglial are autoaggressive immune effectors, reconciles the demonstrated immune effector function of microglia with the claim that an endogenous immune system of the brain must have evolved in order to protect this vulnerable organ from potentially detrimental side effects of a peripheral immune response. There are significant practical implications of these theories for CNS injury and disease. For example, it may be possible to repair axons transected as a result of spinal cord injury by using microglial cell transplants. It may also be possible to selectively stimulate microglia within the immunosuppressive environment of a brain tumor to become tumor cytotoxic effectors that can eradicate malignant glioma cells. Alzheimer’s disease could be a ‘microglial disease’, in the sense that as microglia age and become senescent they may be less able to carry out their normal neuroprotective functions, thus causing neurodegeneration through neglect.

Contact: streit@mbi.ufl.edu


Colin Sumners, Ph.D., University of Southampton, 1980

Primary Department: Physiology and Functional Genomics, COM

Neuro-related research within my group is focused on the neural mechanisms, within the brain, that are involved in stroke and hypertension. Current major areas of research are:

  1. Understanding the potential neuroprotective role of angiotensin receptors during stroke. Our research has determined that angiotensin, acting via its type 2 (AT2) receptors, reduces neuronal death following conditions that mimic stroke in vitro. Our present studies are geared towards determining the mechanisms of this neuroprotection, and the neuroprotective actions of angiotensin in vivo. Methods include cell culture approaches, molecular biology and in vitro/in vivo gene transfer.
  2. Understanding the role of macrophage migration inhibitory factor (MIF)in regulating angiotensin’s actions within the brain. Angiotensin II has a powerful pressor action mediated by its type 1 (AT1) receptors in the hypothalamus and brainstem, and this action is enhanced in and contributes to high blood pressure.

Thus, a major goal of our research has been to define the cellular actions of angiotensin in hypothalamic and brainstem neurons, and understand the factors that regulate angiotensinergic transmission in normal and hypertensive animals. Our studies have demonstrated that angiotensin induces the expression of MIF within the hypothalamus of normotensive rats, and that MIF acts as a negative feedback regulator of AT1 receptor-mediated increases in neuronal firing. However, this MIF-dependent mechanism is absent in the hypothalamus of hypertensive rats. Our present studies are geared towards determining the mechanisms by which angiotensin induces MIF expression in normal rats, and why angiotensin fails to alter MIF expression in hypertensive animals. Further, we aim to define the mechanisms of action of MIF on neuronal firing. Methods used include cell culture and whole animal approaches, electrophysiology, molecular biology and in vitro/in vivo gene transfer.
Contact: csumners@phys.med.ufl.edu


Floyd J. Thompson, Ph.D., Indiana University, 1971

Primary Department: Neuroscience, COM

The research activities of my laboratory are directed towards understanding the neurobiology of the motor system following brain and spinal cord injury. It is our goal to acquire information that can direct the development of specific and effective therapies that can enhance the quality of life for individuals with these types of injuries. Our ongoing work addresses fundamental neurophysiological changes in mechanisms that regulate reflex excitability that lead to the development of spasticity, and how these insights can guide the development of effective therapies. Currently these studies include a comparison of two different types of therapeutic exercise to induce activity-directed neuroplasticity of the motor system in the setting of chronic spinal cord injury. In our laboratory, one set of these studies is being conducted in a rodent model, with Dr. Prodip Bose serving as principal investigator. In a parallel set of studies, we are collaborating with Dr. Andrea Behrman, Dept. of Physical Therapy, who is studying therapeutic exercise enhancement of basic neurophysiological mechanisms that influence human locomotion following incomplete spinal cord injury. More recently, in collaboration with the Dr. Ron Hayes Laboratory of the Center for Traumatic Brain Injury Studies at the McKnight Brain Institute, we are developing a traumatic brain injury (TBI) model to address several urgent issues related to the development and treatment of TBI-spasticity resulting from cortical contusion injury. These studies have revealed new information regarding the nature, time course, and magnitude of spasticity following TBI. Ongoing studies utilizing this model will evaluate early intervention strategies that could intercept and decrease the severity of TBI-spasticity. Finally, in collaboration with the Dr. Robert Yezierski and Dr. Robert Caudle laboratories of the Comprehensive Center for Pain Research at the University of Florida, we are developing a model of closed head injury to extend our studies to address an additional head injury population. The objective of these studies is to combine expertise to collectively enhance our understanding of correlated changes in sensory and motor function following closed head type of brain injury.

Contact: thompson@mbi.ufl.edu


Nihal Tümer, Ph.D., Hacettepe University, Turkey, 1981

Primary Department: Pharmacology and Therapeutics, COM

The incidence of cardiovascular diseases increases in the elderly. In particular, the elderly do not regulate blood pressure as well as young people. The focus of our research is to investigate the loss of plasticity in catecholamine biosynthesis with age. The mechanisms involved in catecholamine biosynthesis, especially the induction of tyrosine hydroxylase (TH) are assessed at the molecular level by determining gene expression. In addition cAMP, cGMP-mediated as well as protein kinase-C signal transduction pathways in the peripheral and central nervous system are being investigated. Our goal is to understand the regulation of catecholamine biosynthetic enzymes and their role in hypertension, heart disease, stress and aging. Also, our recent interest centers on gene delivery, specifically GDNF, in hypothalamus to reverse the age-related decline in TH expression.

Contact: ntumer@ufl.edu


Krista E. Vandenborne, Ph.D., Free University of Brussels, 1993

Primary Department: Physical Therapy, CHP

Dr Vandenborne’s work presents a multidisciplinary, integrated research approach to study muscle degeneration/regeneration from a pathophysiological level to functional impairment. The specific objectives of her program are to: 1) develop novel noninvasive techniques for the evaluation of skeletal muscle, 2) investigate the ability to enhance muscle function using modalities ranging from gene transfer, to exercise training and pharmacological treatment (hormonal supplement), and 3) examine the physiological process(es) essential to the repair of skeletal muscle and return of functional ability. Her current funded projects focus on the pathophysiology of muscle atrophy and muscle regeneration after limb disuse and the use of viral mediated gene transfer of IGF-I to enhance muscle rehabilitation.

Contact: kvandenb@hp.ufl.edu


Thomas W. Vickroy, Ph.D., Professor,

Primary Department: Physiological Sciences

The general research focus of my laboratory involves the neurochemical and molecular bases for chemically-mediated synaptic transmission in CNS pathways. Specific projects involve the following:

  1. understanding the functional roles of presynaptic autoreceptors that regulate the release of acetylcholine, glutamate and other neurotransmitters;
  2. understanding the role of glutamate transporters in the pathophysiological consequences of acute episodes of hypoxia and ischemia;
  3. understanding the role of protein phosphorylation/dephosphorylation as a pathway for regulating transporter function; and
  4. understanding cellular control mechanisms for regulating extracellular levels of excitatory transmitters during periods of heightened neuronal activity.

The overall aim of these investigations is to obtain a more complete understanding of chemical neurotransmission and to identify molecular targets for drugs which may reverse specific changes brought about by certain diseases or neuropathological conditions.

Trainee Participation In this Research: Students involved with these research projects are trained to utilize a variety of techniques in order to gain a more thorough appreciation of the biochemical and molecular bases for neuronal communication. Students are trained to conduct a variety of investigations in isolated tissue preparations, including methods to investigate drug-receptor interactions, regulation of intraneuronal second-messenger molecules, and methods to assess the release, metabolism or uptake of various neuroactive compounds.

Contact: vickroyt@mail.vetmed.ufl.edu


Keith D. White, Ph.D., Brown University, 1976

Primary Department: Psychology, CLAS

Imaging core of Brain Rehabilitation Research Center program project grant: fMRI used to measure perilesional or contralateral brain activation in aphasic patients undergoing different forms of therapy. Perceptual changes in psychiatric disorders: perceptual alternation times series, as from binocular rivalry or ambiguous figures, studied in patients with schizophrenia, bipolar disorder, or PTSD (for examples) and also studied in their relatives.

Contact: kdwhite@ufl.edu


Charles G. Widmer, D.D.S., Emory University, 1981; MS, Oral Sciences, SUNY/Buffalo, 1983

Primary Department: Orthodontics, COD

The general focus of my research program is in the area of masticatory muscle form and function and includes developmental features, functional architecture, motor control mechanisms, and mechanisms of muscle pain. Multiple species are examined including mouse, rabbit and human to adequately explore these topics. Sex-based differences are also an integral part of this work. The overall goal of these studies is to better understand the normal form and function of these muscles during development and in the adult. This work forms a basis for understanding pathological masticatory muscle conditions such as chronic muscle pain as well as re-innervation and repair after injury.

Contact: widmer@dental.ufl.edu


Charles E. Wood, Ph.D., Univ. of California, San Francisco, 1980

Primary Department: Physiology and Functional Genomics, COM

Present work in this laboratory focuses on three projects:

  1. the interaction of prostanoids with the cardiovascular and endocrine controlling elements of the brain and the role of the locally-generated prostanoids in brain in the control of fetal stress responses (hypoxia and hypotension);
  2. the influence of estrogen on the fetal brain regions which are important for cardiovascular and endocrine responsiveness to stress; and
  3. the biological activity of sulfoconjugated estrogens in fetal plasma.

This work is predicated on the observation that the fetal HPA axis is involved both in coordinating fetal stress responses (and thus is involved in the fetal survival of stress) and in coordinating the initiation of parturition. Identifying the basic neural mechanisms controlling fetal HPA function will yield a better understanding of both processes, as well as providing new strategies for therapeutic interventions. On this basic level, information gained in the ovine model will likely be directly applicable to the human being. We have found that prostaglandins generated within the fetal brain exert a profound influence on fetal HPA activity. The fetal response to hypotension, for example, is partially blocked using an inhibitor of prostaglandin biosynthesis. Hypotension stimulates the biosynthesis of the inducible form of the enzyme critically important for prostaglandin biosynthesis, cyclooxygenase-2 (COX-2), within the pathways in the fetal brain which impinge on the paraventricular nucleus, which sits at the head of the HPA axis. However, we have also reported that the expression of both COX-1 and COX-2 are increased in these regions as a function of development, supporting the notion that the increase in HPA axis activity which initiates parturition is itself dependent upon prostaglandin production. Recently, we have explored this ontogenetic regulation by demonstrating that fetal estrogen, which is released by the placenta prior to term, augments COX-2 expression in fetal brainstem and hypothalamus. Finally, we have initiated studies which demonstrate that estradiol-3-sulfate, the most abundant estrogen in fetal plasma, yet a steroid which has long been thought to be inactive, is converted in the fetal brain to its active form, 17ƒr-estradiol, where it increases HPA axis activity. All of these studies, which are funded on multiple extramural grants, will provide a more mechanistic understanding of fetal stress and parturition.

Contact: cwood@phys.med.ufl.edu