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Program Faculty
There
are six departments from which 15 training faculty participate in this
program, all of whom have significant experience in both research and
training. This is one of 9 training grants at UK. In addition to
interacting through the training program many of the training faculty
are members of CDAR and CDART and as such interact on a frequent basis.
All of the training faculty work together in teaching and this endeavor
has further enhanced the cooperation and interactions among the group.
A majority of the training faculty meet regularly as a part of the
“local NIDA”
journal club. This meeting includes graduate
students and postdoctoral fellows participating in the training program
in an informal atmosphere at an individual’s home. These events
solidify the comradely between training faculty and trainees.
There
are a number of indicators of the strengths of training faculty given in
the tables below. This includes their research strength as indicated by
extramural funding. Together the training faculty receive ~$9,5 million
in direct cost research funding from NIDA, and a total of more than $16
million in overall direct cost research funding.
All of
the training faculty has experience training pre and postdoctoral
fellows. They have been successful in placing their trainees in
excellent positions in academia and industry. Each of the
participating departments has a strong record of attracting students and
fellows and providing state of the art training enabling their trainees
to compete for excellent career positions in academia, industry, and
non-traditional scientific careers.
The
attached biographical sketches of the training faculty further
demonstrate the strength of the training faculty as indicated by their
research publications, memberships on NIH and other review panels,
membership on editorial boards, scientific service, and presentations at
national and international meetings.
Louis B. Hersh - Program
Director
Dr Louis
B. Hersh will continue serve as Director of this Training Program. Dr.
Hersh has been continuously funded by NIDA for research on the
metabolism of opioid peptides since 1977. He has been the recipient of
an NIH Research Career Development Award, and as noted above has served
on a number of NIH study sections.
The
research conducted in Dr. Hersh's laboratory focuses on neuropeptidases
and their action on opioid and related peptides. These studies include
the characterization of a puromycin sensitive aminopeptidase implicated
in neuropeptide metabolism and recently reported to be a major catabolic
enzyme for tau and studies on the endopeptidases neprilysin, (“enkephalinase”).
In addition to being a major regulator of enkephalin levels, neprilysin
is involved in peptide hormone regulation in a number of tissues and is
implicated in regulating chemotaxis and pain. Recently this enzyme has
been shown to be a major regulator of amyloid beta peptide levels, and
studies are currently underway to study the involvement of neprilysin in
this process.
Studies
are also being conducted on the enzyme insulysin (insulin degrading
enzyme), which is a major b-endorphin metabolizing enzyme and another
peptidase that metabolizes amyloid b peptides in brain. Insulysin is
unique in that it is allosterically regulated, with activation toward
the hydrolysis of dynorphins by small molecules. In collaboration with
Dr. David Rodgers, a member of the training faculty, the three
dimensional crystal structures of insulysin, and the puromycin sensitive
aminopeptidase have been solved and provide new insights into structure,
function, and regulation. These structures are currently being used to
study the mode of action of these neuropeptidases and to design small
molecule effectors.
Linda Dwoskin -
Co-Director.
Dr.
Dwoskin is an Endowed Professor in the Department of Pharmaceutical
Sciences in the College of Pharmacy. The major focus in her laboratory
is drug discovery in the area of neuropharmacology, specifically the
development of novel therapies for the treatment of psychostimulant
(methamphetamine, cocaine and nicotine) abuse. Novel analogs are
evaluated to elucidate their mechanism of action and ability to modulate
dopaminergic, noradrenergic and serotonergic neuronal function with
respect to effects on neurotransmitter release, uptake, metabolism,
storage and interaction with postsynaptic receptors. Pharmacophores for
specific nicotinic receptor subtypes, neurotransmitter transporters and
the vesicular monoamine transporter are being developed through the
generation of structure activity relationships. Currently, Dr. Dwoskin
is the PI of an NIH RO1 to pursue her drug discovery efforts for the
treatment of methamphetamine abuse and the PI and Director of a National
Cooperative Drug Discovery Grant (NCDDG) to pursue tobacco smoking
cessation agents. She is also the PI of an R21 grant to study the
modulation of nicotinic receptors on dopamine transporters to better
understand the effect of nicotine on the dopaminergic presynaptic
terminal. On two additional projects (a Center grant and an RO1) funded
by NIDA, she serves as co-PI to study the role of genetic factors and
environmental factors as determinants of individual responsiveness to
drugs of abuse and as determinants of an individual's potential for
abuse liability using animal models. Dr. Dwoskin has served on a number
of NIDA and NIH review committees. She currently mentors four
predoctoral students and six postdoctoral fellows. Additionally, Dr.
Dwoskin has served as a member of 40 Ph.D. thesis committees, and has
mentored 15 undergraduate students from various programs at UK who have
performed research in her laboratory during the academic year and summer
months.
Sharon Walsh - co-Director
Dr.
Walsh is Professor of Behavioral Science, Psychiatry, and Executive
Director of the Center on Drug and Alcohol Research. Prior to coming to
UK in 2005, Dr. Walsh earned her M.S. (1987) and Ph.D. (1990) from
Rutgers University
in Behavioral Neuroscience. Dr. Walsh joined the Behavioral
Pharmacology Research Unit at
The Johns Hopkins
University School of Medicine in 1990
as a postdoctoral fellow where she trained in human behavioral
pharmacology. She joined the faculty in 1992 and in 2003 became
Professor of Behavioral Science and Psychiatry. Dr. Walsh's clinical
research has focused on pharmacological issues in opioid and cocaine
dependence. She has conducted studies on pharmacodynamic and
pharmacokinetic characteristics of opioid treatment agents, including
buprenorphine, methadone and LAAM and has evaluated potential
pharmacotherapies for efficacy and safety in the treatment of cocaine
dependence. Dr. Walsh was the 1997 recipient of the Presidential Early
Career Award for Scientists and Engineers, has authored numerous papers,
has served as a regular NIDA study section member and serves on the
board of an array of professional associations in the field of substance
abuse. She has continued her work at UK where she is conducting
research on prescription opioid abuse and inpatient and outpatient
studies on medications development for opioid and stimulant dependence.
She currently has three R01 awards from NIDA along with
industry-sponsored support for ongoing clinical trials. Her current
awards are focused on clinical pharmacology studies of prescription
opioids, and both laboratory abnd clinic evaluation of novel potential
pharmacotherapies for cocaine dependence, including aripiprazole and
atomoxetine. She has/is also participated in multi-site, national
evaluation studies on the efficacy of lofexidine for opioid
detoxification and vigabatrin for methamphetamine dependence.
Michael Bardo
Dr.
Bardo is a Professor in the Department of Psychology and Director of the
NIH-funded Center for Drug Abuse Research Translation (CDART). His
research laboratory is
primarily interested in understanding the basic neuropharmacological
mechanisms that underlie drug abuse. A major focus of his work is aimed
at determining the impact of environmental factors during development on
the neurobehavioral effects of drugs of abuse, with particular emphasis
on stimulants and opiates. Laboratory rats are raised from weaning to
adulthood in either an enriched or impoverished stimulus environment and
then are tested for drug-induced changes in locomotors activity and drug
reward. Neural correlates of the behavioral changes are being examined,
with specific emphasis on the mesolimbic dopamine reward system.
Individual differences in mesolimbic dopamine reward sensitivity are
also being examined to determine if they are specifically related to the
acquisition and maintenance of stimulant self-administration. In
another line of work, Dr. Bardo is collaborating with Dr. Dwoskin's
laboratory to develop novel pharmacotherapies for the treatment of
psychostimulant (methamphetamine, cocaine and nicotine) abuse. Students
and postdoctoral fellows trained in his laboratory are exposed to a
variety of behavioral protocols, as well as techniques in small animal
surgery, in vivo microdialysis, HPLC analysis and histological
staining.
Wayne Cass
Dr.
Cass is a Professor of Anatomy and Neurobiology. His research focuses
on the in vivo regulation of dopamine release and uptake,
including how methamphetamine and other drugs of abuse and neurotoxins
affect dopamine systems. The primary techniques used in his lab are
in vivo microdialysis, in vivo voltammetry, and HPLC. Dr.
Cass’ recent publications include papers on methamphetamine
neurotoxicity, models of aging and Parkinson’s disease, and
neuroprotective and restorative effects of trophic factors and other
compounds on dopamine systems. Dr. Cass has been funded by NIDA to
study short-term and long-term effects of methamphetamine on dopamine
release. He is currently the P.I. on a NIDA R21 grant to examine the
potential protective and restorative effects of calcitriol against the
neurotoxic effects of methamphetamine. Dr. Cass is also the P.I. on an
NIA R01 grant that is examining 6-hydroxydopoamine toxicity in aging
rats, and is P.I. on an NINDS R21 grant to determine if calcitriol can
promote recovery of dopamine neurons in animals treated with the
neurotoxin 6-hydroxydopamine. Dr. Cass is a frequent speaker at
international and national conferences on drugs of abuse, and he has
served on numerous NIH study sections. He has had two Ph.D. students
graduate in the past four years and he is presently on the advisory
committees of six other graduate students.
Peter A. Crooks
Dr.
Crooks is the George A. Digenis Professor in Drug Design and Discovery
in the Department of Pharmaceutical Sciences in the College of
Pharmacy. He received his BS (1966), MS (1967) and Ph.D. (1970) from
the University of Manchester (England), Department of Pharmacy, where he
served on the Faculty from 1968-1981. He carried out his post-doctoral
work at Yale School of Medicine in the laboratory of Dr. James K.
Coward. He joined UK in 1981. Dr. Crooks has graduated 23 Ph.D.
students and 8 M.S. students, and trained 50 post-doctoral fellows and
visiting scientists. His former students and postdoctoral fellows hold
key positions in academia and the pharmaceutical industry. Dr. Crooks’
research interests are in the area of drug discovery and plant natural
product research, and focus on the development of therapeutic agents for
the treatment of central nervous system pathologies and diseases, such
as Alzheimer's disease, Parkinson's disease and Tourette's syndrome. A
major focus is the development of neuronal nicotinic receptor
antagonists for therapeutic use in smoking cessation and the development
of ligands, which interact with the vesicular monoamine transporter as
treatments of methamphetamine abuse. Dr Crooks collaborates with Dr.
Linda Dwoskin on these studies, which are funded by NIDA and the
pharmaceutical industry. A third research area funded by NIAAA focuses
on the design, synthesis, and discovery of neuroprotective agents of
clinical utility in minimizing the neuronal damage that results as a
consequence of detoxification in alcoholism. A fourth area of
collaboration, which is funded by both NIDA and NIAAA, with an other
training faculty Dr. Audra Stinchcomb focuses on the development and
synthesis of codrugs and prodrugs of naltrexone for the treatment of
drug and alcohol abuse. Dr. Crooks is author of over 400 research
articles, and holds over 70 patents. He is a Fellow of the Royal
Society of Chemistry, a Fellow of the Royal Pharmaceutical Society of
Great Britain, and a Fellow of the American Association of
Pharmaceutical Scientists. He has served on several NIH Study Sections
and was a member of the Office of Extramural Program Review Committee,
Contracts Review Branch, NIH.
Greg A. Gerhardt
Dr.
Gerhardt is Professor of Anatomy & Neurobiology, Neurology, and
Psychiatry. He has a strong record of contributions to the fields of
drug abuse, Parkinson's disease research, aging and the development of
technologies to directly measure neurotransmission in the intact brain.
He has published on the effects of cocaine on brain dopamine systems,
the effects of aging on dopamine release, Parkinson's disease,
electrophysiology of medium spiny neurons, functional MRI in awake
monkeys and the effects of neuronal growth factors, such as GDNF, on
damaged or dying dopamine neurons. Dr. Gerhardt is well-known for his
pioneering work in the development of microelectrodes for measurements
of dopamine, norepinephrine, serotonin, nitric oxide, glutamate, choline
and other neurotransmitters in the brains of rats, mice and monkeys. He
currently receives funding from NIDA through a Stage II CEBRA award to
develop sensors for studies of the effects of drugs abuse on glutamate
and GABA release. This novel technology is being developed with the
support of a number of NIDA-funded laboratories, including Dr. Marina
Wolf, Dr. Peter Kaliva, Dr. Wayne Cass, Dr. Linda Dwoskin and Dr. John
Bruno. He is also the PI on a Morris K. Udall Parkinson's disease
Research Center of Excellence at UK, one of 12 in the United States. He
is a co-investigator on another program project grant with Dr. Don
Gash. In addition, he has numerous grants and contracts from industry
sources. Dr. Gerhardt has funding from the National Science Foundation
for the development of his microelectrode technologies, and is the
Director of the Center for Microelectrode Technology. He is the North
American Editor-in-Chief for the Journal of Neuroscience Methods.
Dr. Gerhardt currently mentors six Ph.D. graduate students.
Jane Joseph
Dr.
Joseph is an Associate Professor in the Department of Anatomy &
Neurobiology. Her laboratory has five major foci of research: 1) the
neural basis of object and face recognition in humans and non-human
primates, 2) the developmental trajectory of the neural basis for object
and face recognition, 3) functional neuroanatomy for object and face
recognition in autism spectrum disorder, 4) neural basis of cognitive,
emotional and motivated behavior in individuals at risk for drug abuse,
and 5) neurobiological and functional neuroanatomical sex differences in
cognition. Currently, Dr. Joseph has an NIH R01 on which she serves as
PI to explore the neural basis of face recognition development. In
addition, she serves as PI for a pilot grant from Autism Speaks to
explore functional brain connectivity patterns for face recognition in
Autism Spectrum Disorder. Dr. Joseph also serves as a co-investigator
on a center grant funded by NIDA to explore the neural basis of risk
factors for drug abuse and as a co-investigator on an American College
of Clinical Pharmacy grant to explore the neural basis of craving
reduction by ondansetron in alcoholics. She also serves as a
co-investigator on a center grant to explore the neural basis of drug
and hormone interactions. She has served on NIH review committees and
as a reviewer for over 20 scientific journals. Dr. Joseph is currently
on the editorial board for the Journal of Neuroscience Methods.
She currently mentors two predoctoral students. Former students in Dr.
Joseph’s lab have been quite successful. Dr. Xun Liu, a former
postdoctoral fellow, is now a Research Assistant Professor at Mt. Sinai
School of Medicine. Dr. Ann Gathers, a former predoctoral student is
now an Assistant Professor at the University of Tennessee at Martin.
Dr. Michael Cerullo, a former postdoctoral fellow, is now a Clinical
Assistant Professor at the University of Cincinnati. Dr. Joseph has
also mentored high school and undergraduate students. Nick Steinmetz, a
former high school student in her lab, is now a graduate student at
Stanford University. Stephen Foldes, a summer undergraduate student, is
now in graduate school at Case Western Reserve University.
Kim Nixon
Dr. Nixon is
an Assistant Professor in the Department of Pharmaceutical Sciences.
Her laboratory is broadly interested in mechanisms of neurodegeneration
and regeneration in alcoholic neuropathology and recovery in abstinence
respectively. She investigates the role of neural stem cells in the
adult brain (i.e. adult neurogenesis) in regions that are commonly
affected in alcohol use disorders. She was the first to show that
alcohol intoxication inhibited adult neurogenesis in her postdoctoral
work, and her lab now focuses on understanding the factors that regulate
adult neurogenesis and their contribution to brain and behavioral
processes in alcoholic neuropathology. A secondary goal is to identify
a novel signaling cascade that may be harnessed for pharmacological
treatment of alcohol-induced neurodegeneration.
Dr. Nixon’s
is PI on three NIH funded projects. The major project investigates the
mechanism of a reactive burst in neurogenesis following binge alcohol
exposure with a broad goal of understanding the relationship between
microglia reactivity and neurogenesis. A second project investigates
whether neural stem cells contribute to neurodegeneration in an
adolescent model of alcohol abuse and tacit to that is comparisons of
cell death and cell birth processes between adult and adolescent models
of alcohol use disorders. Dr. Nixon also serves as PI on a Phase I STTR
grant in collaboration with AllTranz and its founder, Dr. Audra
Stinchcomb (training faculty) to investigate a cannabinoid agonist as a
treatment for alcohol use disorders. She currently mentors two graduate
students and two postdoctoral fellows will join her program in summer
2008. Her student Stephanie Morris has received a Research Society on
Alcoholism Student Merit Award for 2007 and 2008.
William Maragos
William
F. Maragos, M.D., Ph.D. is an Associate Professor in the Department of
Neurology. He carries joint appointments in the Department of Anatomy
and Neurobiology, the Graduate Center for Toxicology and is an Associate
in the Sanders Brown Center on Aging. Dr Maragos holds an American
Heart Association Bugher award the major goal of which is to elucidate
the protective mechanism of “mild uncoupling” in a rodent model of
transient cerebral ischemia. He is also Co-investigator on a VA Merit
Award designed to elucidate the protective mechanism of the novel
mitochondrial permeability transition inhibitor, NIM811, in a model of
transient cerebral ischemia.
Jim Pauly
Dr. Pauly is an Associate Professor of
Pharmaceutical Sciences in the College of Pharmacy. Dr. Pauly has
published over 45 papers and 80 abstracts and has received funding from
NICHD, NIDA, NINDS and the pharmaceutical industry. He is currently a
member of the BDCN-2 NIH study section and has also reviewed proposals
for the Alzheimer's Association, and Phillip. Dr. Pauly's research
program is focused on the neurobiology of neuronal nicotinic receptor
subtypes. He is currently studying the role of nicotinic receptors in
tobacco addiction as well as native functions of nicotinic receptor
subtypes in brain development. Behavioral, pharmacological and cellular
approaches are used to study nicotinic receptor neurobiology. He is
evaluating the effects of prenatal nicotine exposure on the development
of 1) the cerebellar architecture and 2) dopaminergic neurons. It is
believed that in utero exposure to nicotine causes a disruption of
normal brain development. Increasing evidence points to nicotine as a
behavioral teratogen. The hypothesis that in utero exposure to nicotine
causes a disruption of normal neurobehavioral development is currently
being tested. Dr. Pauly currently has two PhD students working in his
laboratory.
Mark Prendergast
Dr.
Prendergast is an Associate Professor of Psychology whose research focus
is behavioral neuroscience. Specifically, Dr. Prendergast’s research
focuses on the means by which long-term ethanol exposure sensitizes the
brain to neurotoxic effects of HIV1-related transcriptional proteins and
other substances that activate the NMDA-type glutamate receptor system.
Further, this work examines novel pharmacologic strategies that may be
employed to attenuate this neurotoxicity, namely, allosteric modulation
of a polyamine-sensitive portion of some NMDA receptors and agonism of
neuronal nicotinic receptors. The primary aim of these studies is to
elucidate receptor-mediated mechanisms that may be involved in
alcoholism-related neurodegeneration and to assess novel
pharmacotherapeutic interventions for the treatment of this toxicity.
Dr. Prendergast has been the PI of an NIAAA funded grant to examine
these issues. Dr. Prendergast currently mentors several undergraduate
research students and two graduate students, as well as one Postdoctoral
Fellow/Research Associate who has obtained independent extramural
funding.
David Rodgers
Dr.
Rodgers is an Associate Professor of Molecular and Cellular
Biochemistry. He has a strong record of contributions to the field of
structural biology and to the development of techniques in
macromolecular X-ray crystallography. Dr. Rodgers has published in the
areas of protein-nucleic acid interactions, nucleic acid polymerase
mechanisms, peptidases, and flavoenzymes. He is well known for his
pioneering work in cryogenic data collection techniques for x-ray
crystallography. He has contributed to our knowledge of HIV structural
biology by determining the crystal structure of the HIV reverse
transcriptase enzyme in an unliganded form. Dr. Rodgers also
participated in the structure determination of the CD4 molecule, the
primary HIV receptor on the host cell surface, and has worked with a
number of viral transcriptional regulatory proteins. Dr. Rodgers is the
P.I. of an NIH R01 grant that focuses on investigating the mechanistic
basis for substrate recognition and function of neuropeptidases.
Together with Dr. Louis Hersh, he is Co-PI on an R01 grant from NIDA
that focuses on opioid peptide metabolizing enzymes. Neuropeptidases, a
major focus of Dr. Rodgers’ research, play critical roles in the central
nervous system and are excellent targets for therapeutic intervention in
addiction and disease processes. Inhibitors of neuropeptidases are
already in widespread use as antihypertensives and have been proposed
for the treatment of drug and alcohol abuse. Dr. Rodgers attempts to
understand the basis for the complex patterns of substrate recognition
in these enzymes and to reengineer these enzymes for therapeutic uses.
He also collaborates with a pharmaceutical company to develop inhibitors
for psychotic disorders and addiction. Dr. Rodgers helps to direct the
Center for Structural Biology at UK and serves on the Executive Board of
the Southeast Synchrotron Radiation Consortium. He currently mentors
two Ph.D. graduate students. His graduates have taken postdoctoral
positions at California Institute of Technology, Johns Hopkins
University, Harvard University, Yale University, and the National
Institutes of Health.
Audra L. Stinchcomb
Dr.
Stinchcomb is an Associate Professor in the College of Pharmacy
Department of Pharmaceutical Sciences. Dr. Stinchcomb’s major research
interest is percutaneous absorption. Research investigations include
transdermal and topical drug delivery, dermal metabolism, and risk
assessment involving dermal absorption of toxic chemicals. The
transdermal and topical drug delivery focus has been on efforts to
improve delivery of drugs by altering their physicochemical properties,
i.e. via prodrugs and codrugs (mutual prodrugs). Her specific
therapeutic areas of interest include cannabinoid therapies and
treatments for opiate, tobacco and alcohol abuse. She received an
American Cancer Society grant for transdermal cannabinoid work as a new
investigator. Dr. Stinchcomb is the PI on two NIH R01 grants for the
development of transdermal therapies for opiate/alcohol abuse (NIDA) and
tobacco/alcohol abuse (NIAAA). She is also Co-I on a NIDA R01 for
development of a programmable transdermal delivery system for smoking
cessation and opiate withdrawal therapy. Dr. Stinchcomb has served as
an ad hoc grant reviewer for NIH, and on a SBIR/STTR NIH study section.
Three postdoctoral fellows were mentored by Dr. Stinchcomb in 2006-08,
and currently she mentors four predoctoral students.
Chang-Gou Zhan
Dr.
Zhan is a Professor in Pharmaceutical Sciences at the College of
Pharmacy. Dr. Zhan’s main research interest is drug design and
discovery through integrated computational-experimental studies. Drugs
designed and discovered in Dr. Zhan’s lab are either small molecules (as
inhibitors of enzymes or agonists/antagonists of receptor proteins or
DNA-binding molecules) or engineered proteins (mutants with
significantly improved biological functions and/or increased circulation
time in the body). In order to rationally design a drug, Dr. Zhan’s lab
performs various types of molecular modeling (including homology
modeling and molecular docking), simulations (e.g. MD and Monte Carlo),
calculations (e.g. QM, QM/MM, MM-PBSA, and FEP), statistical analysis
(including QSAR and Artificial Neural Network), and molecular design
(automated virtual screening and de novo design) that are necessary for
a project. The computational design is followed by wet experimental
tests (chemical synthesis, site-directed mutagenesis, protein
expression, purification, in vitro activity assays, and in vivo tests).
These experiments are performed either in Dr. Zhan’s lab or in a close
collaboration with internal and/or external experimental laboratories.
Dr. Zhan’s NIDA supported unique “structure-and-mechanism-based drug
design and discovery” efforts through integrated
computational-experimental studies have been very productive, leading to
exciting discoveries of novel, promising therapeutics. Dr. Zhan has
published more than 180 peer-reviewed papers on a wide range of topics
and has recently submitted five patent applications.
As
indicated above, a strength of this training program is the interactive
nature of the faculty and the extensive collaborations that are
ongoing. A number of these collaborations are longstanding and involve
collaboratively funded research programs i.e. Hersh-Rodgers,
Dwoskin-Crooks-Bardo, Nixon-Stinchcomb, etc.) while others have more
recently developed. |
