Specialty/Research Focus:
Drug abuse; Circadian Rhythm/Chronobiology; Gene Expression; Molecular and Cellular Biology; Neuropharmacology
Research Summary:
My laboratory seeks to understand the neurobiology of motivation and how these systems can be "highjacked" by abused substances. Substance abuse and addiction are wide-spread problems that have an enormous economic and emotional toll. Reports indicate that it costs the US upwards to $600 billion a year to deal with the health and criminal consequences and loss of productivity from substance abuse. Despite this, there are few effective treatments to combat this illness.
The brain has natural systems responsible for motivating an organism to participate in behaviors that are necessary for survival, such as eating, exercise and reproduction. These same brain regions are highly sensitive to drugs of abuse, including cocaine, heroin and marijuana. My laboratory seeks to understand how these brain regions are affected by exposure to abused drugs, and in particular how the motivation to take drugs is altered by various molecular mediators in the neurons on these regions. The two basic questions we are interested in are 1) how projections from the cortex to the striatum influence drug seeking behaviors, and 2) how neurotransmitter receptors, particularly dopamine and cannbinoid receptors in these regions influence drug seeking.
Our technical approaches include a number of basic behavioral models including measurements of locomotor activity, catalepsy, conditioned place preference and drug self-administration. In order to probe the circuitry of these brain regions, we use a number of advanced molecular techniques to activate and inactivate neuronal populations including optogenetics and artificial receptors. We probe the molecular pathways within the neurons by over expressing genes or knocking down expression using RNA interference. Gene delivery is accomplished using recombinant adeno-associated virus (rAAV) and several projects in the laboratory focus on improving this approach and exploring potential gene therapy applications for these vectors. The ultimate goal is to understand the basic neurobiology and molecular biology of addiction in order to develop more effective treatments for addiction.
Specialty/Research Focus:
Molecular and Cellular Biology; Protein Function and Structure; Neuropharmacology
Specialty/Research Focus:
Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular and Cellular Biology; Neurobiology; Pathophysiology; Gene Expression; Signal Transduction
Research Summary:
Neuronal firing patterns are highly diverse because neurons regulate a wide variety of different behaviors and physiological functions including cognition and memory. Whether a neuron exhibits regular spiking, burst firing, adaptation or high frequency firing will largely be determined by which specific ion channel genes a neuron chooses to express. I am interested in a class of potassium channels that are sensitive to intracellular sodium. There are two members in this family, known as Slack and Slick, and both channel subunits are expressed in many different types of neurons. I am particularly interested in how these channels contribute to the firing patterns of pain-sensing neurons and neurons of the cerebral cortex. Understanding when, where and how these channels are working should provide important information on sensory and cortical processing and will provide insights on nociception, psychiatric disorders such as schizophrenia and bipolar disorder and neurological diseases such as epilepsy.
Specialty/Research Focus:
Reproductive Endocrinology; Apoptosis and cell death; Cell growth, differentiation and development; Endocrinology; Gene Expression; Molecular genetics; Signal Transduction; Toxicology and Xenobiotics; Vitamins and Trace Nutrient
Research Summary:
I am an Associate Professor in the Department of Pharmacology & Toxicology of the School of Medicine and Biomedical Sciences. I have a secondary appointment as Adjunct Associate Professor in the Department of Oral Biology in the School of Dental Medicine.
My research interests include the study of how hormones and nutrients affect cell growth, differentiation, and survival. I study these processes in bone osteoblasts and breast normal epithelial cells as well as cancer cells. I have discovered how natural estrogens as well as dietary phytochemicals sustain osteoblast longevity and contribute to bone growth. In collaboration with Dr Atif Awad of the School of Public Health, I have identified dietary factors that inhibit the growth of cancers of the prostate and breast. We have published primary research papers, significant review articles, and two books entitled "Nutrition and Cancer Prevention" and Adipose Tissue and Inflammation".
Specialty/Research Focus:
Molecular and Cellular Biology; Neurobiology; Neuropharmacology
Research Summary:
The core of my current research is ‘systems pharmacology‘, in which I am elucidating the biological function of the novel neuropeptide urotensin II (UII). The characterization of novel neuropeptide systems has been the topic of both my graduate studies (urotensin II; Clark et al., 2001, 2005; Huitron-Resendiz et al., 2005) and my second post-doctoral fellowship (neuropeptide S; Xu et al., 2004; Jüngling et al., 2008; Duangdao et al., 2009; Okamura et al., 2011; Clark et al., 2011). My ultimate research goal is to elucidate the endogenous function of the novel neuropeptide urotensin II. With my existing R00 grant from NIDA, I will establish whether activation of the UII receptor (UIIR) modulates reward behaviors.
In addition, I am currently investigating the nuances of urotensin II receptor signaling and the effects of naturally occurring variants within the coding regions. In these investigations I am furthering my expertise from training I received during my post-doctoral fellowships (Van Craenenbroeck et al., 2005; Clark et al., 2010; Gill et al., 2010). I believe that the parallel investigation of the receptor pharmacology and behavioral pharmacology will expedite the unraveling of the role of the UII system in human biology.
Specialty/Research Focus:
Behavioral pharmacology; Cytoskeleton and cell motility; Gene Expression; Gene therapy; Neurobiology; Neuropharmacology
Research Summary:
Drug addiction is a disabling psychiatric disease leading to enormous burdens for those afflicted, their friends and family, as well as society as a whole. Indeed, the addict will seek out and use illicit substances even in the face of severe negative financial, family and health consequences. It is believed that drugs of abuse ultimately “hijack” the reward circuitry of the CNS leading to cellular adaptations that facilitate the transition to the “addicted” state As is the case with both rodent models of drug taking, and well as throughout the global human population, not all individuals exposed to drugs of abuse will meet the classical definition of being truly “addicted”. Indeed, there is great variability in individual rates of propensities toward relapse following cocaine use., We are looking at how molecular and behavioral plasticity mediates individual differences in susceptibility to drug abuse and relapse.
Specialty/Research Focus:
Drug abuse; Behavioral pharmacology; Signal Transduction; Neuropharmacology; Circadian Rhythm/Chronobiology
Research Summary:
My lab‘s research seeks to understand the mechanism of action of the hormone melatonin at the MT1 and MT2 G-protein coupled receptors. We study these receptors in the brain and through the body with the goal of identifying ligands that exhibit useful binding affinity and therapeutic potential. Our team of undergraduate and graduate students, postdoctoral fellows, technicians and senior scientists work with each other and with expert co-investigators in medicinal chemistry to discover and develop novel molecules that can mimic or counteract the actions of melatonin. These molecules may help treat a variety of diseases and conditions including insomnia, circadian sleep disorders, depression, seasonal affective disorders, and cardiovascular disease.
Our laboratory pursues these investigations from several angles. We assess the localization of the melatonin receptors, examine their cellular and molecular signaling mechanisms,and investigate receptor fate following prolonged exposure to melatonin. We study the distinct roles of selective MT1 and MT2 melatonin receptor ligands in modulating circadian rhythms, methamphetamine‘s ability to induce both sensitization to prolonged exposure, and stimulation of the reward system. We also study cell proliferation, survival, and neurogenesis in the brain, and the changes in gene expression underlying all these processes.
Our research ultimately aims to discover novel drugs with differential actions at the MT1 and MT2 receptors. We use molecular-based drug design, computer modeling and medicinal chemistry to design and synthesize small molecules that target these receptors as agonists, inverse agonists and/or antagonists. We then pharmacologically and functionally characterize these molecules using cell-based assays and bioassays and test them in circadian and behavioral animal models.
Specialty/Research Focus:
Molecular and Cellular Biology; Neurobiology; Gene Expression; Signal Transduction
Research Summary:
Protein phosphorylation is an essential mechanism by which intercellular signals regulate specific intracellular events. Consequently protein kinases, the enzymes catalyzing protein phosphorylation reactions, represent a major superfamily of genes, collectively representing 2% of the protein coding potential of the human genome. Current projects in Dr. Edelman‘s lab are devoted to the role of protein kinases in neuronal development and in specific types of cancer. These projects utilize a wide range of techniques and involve, in the case of the latter project, a collaboration with investigators at Roswell Park Cancer Institute to develop a protein kinase-targeted therapy for prostate cancer.
Specialty/Research Focus:
Molecular and Cellular Biology; Neurodegenerative disorders; Transcription and Translation; Signal Transduction; Toxicology and Xenobiotics
Research Summary:
My lab studies the receptor signaling mechanisms for a family of neurotrophic factors that includes ciliary neurotrophic factor (CNTF), leptin, interferon gamma, and cardiotrophin-1. These factors use the Jak/STAT pathway to regulate neuronal survival, development and response to trauma. Our interests are in how activity of the receptors and their pathway components are regulated. Currently this has focused on the impact of cellular oxidative stress on the inhibition of Jak tyrosine kinase activity. Increases in oxidative stress in neurons result in the blockade of not only CNTF family factor effects, but of many other cytokines that also use the Jak/STAT pathway for signaling such as interferons and interleukins. Non-nerve cells appear resistant to these effects of oxidative stress.
Ongoing projects include testing the theory that environmental contaminants known to increase oxidative stress in cells may promote neurodegenerative diseases by inhibiting growth factor signaling. We have been studying the effects of certain heavy metals (cadmium & mercury) and pesticides (e.g. rotenone) on nerve cells in culture to determine the molecular basis for Jak inhibition.
Another examines a possible role of oxidative stress in obesity. This study tests the hypothesis that the loss of the ability of the hormone leptin to regulate metabolism and appetite during obesity is a result of oxidative reactions that inhibit Jak-mediated signaling in the hypothalamus and other brain regions.
Specialty/Research Focus:
Toxicology and Xenobiotics
Research Summary:
Dr. Paul Kostyniak‘s primary research program has focused on the toxicology of heavy metals, chlorinated organics, and antidote development. His lab is studying mechanisms of xenobiotic disposition and investigating the role of exogenous nutrients in the elimination of toxic pollutants. Other ongoing projects involve the assessment of risk associated with exposure to PCB isomers found in fresh water fish; and the development and testing of antimicrobial surface coatings.
As the director of the Toxicology Research Center, Dr. Kostyniak has organized an interdisciplinary research and teaching program which applies the expertise of toxicologists, pharmacologists, chemists, acquatic biologists, biochemists, pathologists, epidemiologists, geologists and physicians to basic and applied research problems in toxicology. The Center conducts coordinated scientific inquiries into health problems created by toxic chemicals.
Dr. Kostyniak also oversees the center‘s analytical toxicology laboratory and the center‘s Atlantic OSHA Professional Education Program.
Specialty/Research Focus:
Apoptosis and cell death; Endocrinology; Molecular and Cellular Biology; Gene Expression; Regulation of metabolism; Signal Transduction
Research Summary:
Suzanne Laychock, PhD, is senior associate dean for faculty affairs and facilities, and professor of pharmacology and toxicology. She is responsible for overseeing faculty development, space management, and undergraduate biomedical education programs.
Dr. Laychock earned a bachelor’s degree in biology from Brooklyn College, a master’s degree in biology for the City University of New York and a doctorate in pharmacology from the Medical College of Virginia.
An accomplished scientist, Dr. Laychock’s research focuses on endocrine pharmacology with an emphasis on signal transduction mechanisms involved in insulin secretion and models of diabetes mellitus.
The author of numerous journal articles, she has served as associate editor of the research journal LIPIDS, and on the editorial boards of Diabetes and the Journal of Pharmacology and Experimental Therapeutics. She is the recipient of research grants from, among others, the Juvenile Diabetes Research Foundation, the National Institutes of Health, and the American Diabetes Association.
Dr. Laychock is Council Member and has chaired the Women in Pharmacology Committee of the American Society for Pharmacology and Experimental Therapeutics. She has served the university as a member and chair of the President’s Review Board, and as co-director of the Institute for Research and Education on Women and Gender.
Specialty/Research Focus:
Infectious Disease; Bioinformatics; Microbial Pathogenesis
Research Summary:
The major focus of the research in Lesse Lab is the pathogen Staphylococcus aureus. This bacterium is a major cause of infections in both the normal and immunocompromised host. Infections with this organism have a marked propensity to cause both local disease and metastatic complications, including bone infections (osteomyelitis), heart valve infections (endocarditis), and abscesses at critical sites and in critical organs (epidural abscesses, brain abscesses, etc.) In the modern medical era, both intravenous catheters and implanted medical devices are both the source and potential site of infections fro this organism. Although not commonly thought of as an epidemic disease, Staphylococcus aureus has changed markedly over the last 50 years with the rapid development of 4 key characteristics: 1) penicillin resistance; 2) methicillin resistance; 3) toxic shock syndrome; and now 4) community-associated methicillin resistant S. aureus (CA-MRSA) infections. Not only does the pathogen change over time, some features disappear, only to return decades later. In the 1950s serious infections in hospitalized patients were complicated with aggressive local infections and abscess formation. As methicillin-resistance took over the hospital infections, blood stream, pneumonia, and device infection prevailed. Now in the 21st century, locally aggressive infections again prevail with the development of CA-MRSA.
On this background, the laboratory has a major interest in analyzing the potential association between bacterial virulence factors and the development of complications during S. aureus bacteremia. Having conducted a large, three year, prospective, observational study of S. aureus bacteremia in the Western New York area, the laboratory has a well-characterized collection of bacteria to test the hypothesis of that specific virulence factors are associated with complications. The lab utilizes a strong background in pulsed-field gel electrophoresis, along with PCR typing of resistance and virulence associated gene. Collaborating with Dr. Steve Gill, the lab has a keen interest in the development of a Staphylococcal pan-genome array, using bioinformatics to analyze the 18 or greater genomes in the development of a comprehensive array for use in the study,
The lab also has significant interest in CA-MRSA infections in the pediatric population in Western NY. In collaboration with Dr. Howard Faden at the Women and Children’s Hospital, the laboratory has made significant insights into the possible role of rectal colonization in this epidemic pathogen that is sweeping across the US and the world.
Lastly, the lab maintains an interest in bioinformatics in Haemophilus and Moraxella in collaboration with Dr. Timothy Murphy and his extensive research portfolio at the Center for Excellence in Bioinformatic. The work continues the original research focus of the laboratory in both Haemophilus disease, and in particular, the lethal pediatric disease of Brazilian Purpuric Fever.
Specialty/Research Focus:
Cardiovascular Disease; Oncology; Pathophysiology; Regulation of metabolism; Signal Transduction
Research Summary:
My lab primarily seeks to understand the molecular mechanisms of coronary artery disease, the most common cause of age-related cardiovascular disease. I study the signaling mechanisms that underlie the reduced tolerance elderly patients’ hearts show to stress from restricted blood flow (ischemia) and the restoration of normal blood flow (reperfusion). My work aims to devise novel strategies to boost cardiac tolerance of these events in aged populations or prevent patients’ decline in resilience.
Closely tied to this work, my group explores the intrinsic relationship between diabetes and cardiovascular diseases. Evidence suggests that adenosine monophosphate-activated protein kinase (AMPK) may protect the heart from ischemic injury and limit the development of cardiac myocyte hypertrophy. This enzyme is activated by hormones, cytokines, and certain drugs used to treat type 2 diabetes. My lab is investigating AMPK’s role in regulating myocardial glucose metabolism. AMPK binds to adenosine monophosphate (AMP), through which it moderates enzymatic activity, balancing cellular production and consumption of adenosine triphosphate (ATP). We want to elucidate the molecular mechanisms responsible for AMPK activation, identify novel downstream AMPK targets and develop therapeutic techniques that target the enzyme to prevent and treat myocardial ischemia, cardiac hypertrophy and diabetes.
AMPK also shows potential as a drug target for cancer treatment because it may work as an antioxidant, modulating the levels of reactive oxygen species in tumor cells. Building on our understanding of these processes, my group has demonstrated that natural antioxidants extracted from Chinese herbal medicines inhibit the proliferation of tumor cells via related processes. We currently aim to determine these substances’ signaling targets in tumor cells and to develop cancer therapies based on natural products from herbal medicines.
Specialty/Research Focus:
Behavioral pharmacology; Drug abuse; Neurobiology
Research Summary:
The primary research interest in my laboratory is to seek novel pharmacotherapy for pain. Pain is an agonizing symptom and disease that impacts millions. Analgesics like opioids (e.g., OxyContin) are powerful for treating many pain conditions. However, opioids are not efficacious for some pain (e.g., neuropathic pain) and prolonged use of opioids has many side effects, including tolerance and dependence. We utilize two strategies to attack these problems.
1) Develop new analgesics with novel mechanisms of action. Increasing evidence suggest that drugs acting on imidazoline I2 receptors may produce analgesic effects that are devoid of opioid-like side effects. We are working with medicinal chemists to delineate the pharmacological properties of these drugs (how they work, how effective and safe they are, and how long the beneficial effects last).
2) Combine opioids with other analgesics such as imidazoline I2 receptor agonists to treat pain (combination therapy). Like the treatment of cancer and hypertension, combining two analgesics that work through different mechanisms may achieve the same or bigger therapeutic effects with smaller doses, which in turn may produce less side effects (e.g., tolerance and addiction). We are using quantitative pharmacology techniques to understand the nature of these drug interactions for pain treatment.
One unifying theme of the ongoing research is the application of receptor theory to the guidance and interpretation of the drug interactions in behaving animals. The long-term goal of this laboratory is to develop new analgesics without OxyContin-like side effects.
Specialty/Research Focus:
Toxicology and Xenobiotics
Research Summary:
Assessing the Health Risks of Exposures to Organophosphate (OP) Pesticides
• Characterization of the in vitro and in vivo metabolism and disposition of OP pesticides in animal models and humans.
• Identify new biomarkers of susceptibility to OPs by investigating the function of genetic variants in key enzymes (CYP2B6, CYP2C19, PON1) which regulate OP metabolic activation and detoxification.
• Investigate the relationship between biomarkers of exposure, effect and susceptibility in human populations with environmental and occupational exposures to pesticides.
• Utilize enzyme-specific physiologically based pharmacokinetic /pharmacodynamic (PBPK/PD) models to better assess human exposure, target tissue dose and subsequent effects of OPs.
Assessing the Biological and Toxicological Effects of Exposures to Persistent Halogenated Aromatic Hydrocarbons, Including Dioxins, Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs).
• Assessing Human Exposures to dioxins, PBDEs, and PCBs
• Characterize the metabolism and disposition of dioxins, PBDEs, and PCBs in humans.
• Utilize toxicogenomic approaches to understand the relationship between exposures to dioxins and/or PCBs that are ligands for the Ah receptor and mechanisms for their adverse health effects.
Specialty/Research Focus:
Drug abuse; Apoptosis and cell death; Molecular and Cellular Biology; Neurobiology; Signal Transduction; Toxicology and Xenobiotics
Research Summary:
My laboratory is focused on understanding the molecular and cellular actions of drugs of abuse such as ethanol and hallucinogens such as lysergic acid diethylamide (LSD). This information is a requisite step in the ultimate development of therapeutic interventions to alleviate the major healthcare and social burden associated with use and abuse of these drugs. In addition, these drugs provide an avenue to explore the basic workings of the brain under pathological conditions that are manifested as various psychiatric disorders. Previous studies, in collaboration with Dr JC Winter in the Dept of Pharmacology and Toxicology at UB, have investigated the roles of the various serotonin receptors subtypes and their associated signaling pathways as well as glutamatergic neurotransmission in the subjective effects of LSD-type hallucinogens. Our other studies have been aimed at understanding the adverse developmental effects of ethanol exposure that result in the fetal alcohol spectrum disorders with the fetal alcohol syndrome (FAS) as the most severe manifestation. Using zebrafish and neuronal cells in culture as model systems, my laboratory in collaboration with Dr CA Dlugos in the Dept of Pathology and Anatomical Sciences at UB have investigated the morphological and histological changes associated with ethanol exposure during different developmental stages as well as the mechanisms by which developmental ethanol exposure causes neuronal loss.
Currently, we are investigating the neurotoxic interaction of ethanol with pesticides. Because of the wide-spread use of pesticides, people are continually exposed both voluntarily and involuntarily to an array of toxic chemicals. In addition, since consumption of alcohol is pervasive in our society with a very high prevalence of alcohol use and abuse, it is extremely likely that people with be co-exposed to both ethanol and pesticides. Because simultaneous or sequential exposure to multiple chemicals can dramatically modify the ensuing toxicological responses, we are using both in vitro (e.g., cells in culture) and in vivo (e.g., zebrafish) model systems to begin assessing the possible health risk of co-exposure to ethanol and pesticides. Using the herbicide paraquat, which is widely used throughout the world, as a test compound, we have found that ethanol synergistically increases the in vitro neurotoxicity of this pesticide. Our efforts are now aimed at ascertaining whether a similar interaction occurs in vivo as well as determining the molecular mechanism responsible for this synergistic neurotoxicity.
Teaching is a naturally complement to research. Accordingly, I have also been engaged in efforts to both improve how we provide the knowledge base to our undergraduate, graduate, and professional students, and also how we help students learn to integrate and apply this information in problem-solving at the clinical and basic science levels. Efforts include: 1. using “clickers” in large class formats to assess student’s understanding of the material and well as provide each student instantaneous feedback for their own self-assessment; 2. using cases studies and a small group learning format; and 3. Having students write short grant proposals based upon the current literature as well as reviewing and critiquing their classmate’s proposals.
Specialty/Research Focus:
Bioinformatics; Genomics and proteomics; Signal Transduction; Toxicology and Xenobiotics
Research Summary:
Our laboratory seeks to understand hormone-triggered nuclear receptor signaling. Nuclear receptors are associated with various diseases including diabetes and cancer and the availability of several high resolution structures of their ligand binding domains make them attractive targets for drug discovery. Eight of the top 100 prescription drugs (accounting for about US $9 billion in sales) target a nuclear receptor. However, these drugs can cause a variety of side effects and some patients develop drug resistance.
Tamoxifen, a drug designed to selectively target the nuclear estrogen receptor which is present in 70% of breast cancer patients, induces substantial regression of breast tumors and an increase in disease-free survival. Tamoxifen binds directly to the ligand binding domain of estrogen receptor and regulates estrogen-mediated growth of breast cancer cells. Tamoxifen mimics estrogen effects in other tissues thereby providing some beneficial effects including reduced risk of osteoporosis. However, breast cancers that initially respond well to tamoxifen tend to develop resistance and resume growth despite the continued presence of the antagonist.
We specifically focus on protein interactions that regulate estrogen signaling by binding to estrogen receptors. Our objective is to identify the estrogen receptor conformation-sensing regions of the interacting proteins and to discover potential small molecule sensors using state-of-the art bioinformatics and structure-based discovery tools and use them to generate a new breed of small molecular therapeutics for breast cancer therapy.
Specialty/Research Focus:
Neurodegenerative disorders; Apoptosis and cell death; Membrane Transport (Ion Transport); Proteins and metalloenzymes; Signal Transduction; Toxicology and Xenobiotics
Research Summary:
Dr. Jerome Roth‘s research interests over the past several years have focused on the mechanism of action of manganese in producing neuronal cell death. Manganese is an essential mineral that at high concentration acts as a neurotoxin which produces a Parkinson-like syndrome. Although the identified brain lesions associated with manganism differ from those of Parkinson’s disease, there is increasing evidence that chronic exposure to Mn correlates with increased susceptibility to develop Parkinsonism. Current studies are focused on characterizing the signal transduction pathways stimulated by manganese and to determine whether they also play a role in the toxic actions of this divalent cation. As part of this project we are also investigating the transport mechanisms by which manganese is taken up into cells. We have focused our studies on the divalent metal transporter (DMT1) and its role in the transport of manganese and other divalent cations. We are currently studying the transcriptional and post-translational factors that regulate its expression in vivo. Preliminary studies have linked DMT1 expression to the protein, parkin, mutations in which lead to early onset of Parkinson‘s disease. Whether other gene linked to Parkinsonism are also associate with development of manganism is the current focus of my research. Current studies in my laboratory focus on how other early and late genes associated with Parkinson’s disease can influence Mn toxicity as these studies will provide a basis for the comorbidity between manganism and Parkinson’s; the manipulation of this mechanism may therefore provide new prophylactic and/or management treatment options for Parkinson’s disease.
Specialty/Research Focus:
Genomics and proteomics; Molecular and Cellular Biology; Regulation of metabolism; Toxicology and Xenobiotics
Research Summary:
Dr. David Shubert has been at the University at Buffalo since 2006. He received is B.S in Pharmacy from Duquesne University and a Ph.D from the University at Buffalo. His research interests include the mechanism by which environmental chemicals initiate and promote cancer. He is the Assistant Dean for Biomedical Undergraduate Education and teaches pharmacology, toxicology and cardiovascular physiology. Dr. Shubert accepts undergraduate students interested in pursuing research in his areas of interest. He is an active member of the Society of Toxciology.
Specialty/Research Focus:
Genomics and proteomics; Neurobiology; Neurodegenerative disorders
Research Summary:
My lab investigates the molecular control of cell fate and homeostasis of resident stem and progenitor cells in the human brain. Using a combination of multicolor cell sorting techniques and whole genome analysis, we are characterizing the signaling pathways which regulate the formation and fate of human oligodendrocyte progenitor cells. We are testing the functional significance of these pathways using both pharmacological and viral methods in culture and animal-based models of myelination and demyelination.
Specialty/Research Focus:
Behavioral pharmacology; Cardiac pharmacology; Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular Basis of Disease; Neurobiology; Neuropharmacology; Signal Transduction; Transgenic organisms
Research Summary:
With over 400 genes coding for them in humans, ion channels play a significant role in most physiological functions. Drug-induced channel dysfunction often leads to a variety of disorders and results in significant incidence of serious injury and death. We investigate molecular mechanisms underlying neurodegenerative disorders and cardiac arrhythmias induced by ion channel dysfunction arising from genetic factors and/or drug interactions. The tools used for these investigations include genetic, electrophysiologic, pharmacologic, molecular and cell culturing methods. Preparations used for in experiments include Drosophila as a genetic model system, and human cell lines expressing human ion channels that play an important role in critical-to-life functions including cardiac rhythm, respiration and the central nervous system.
Specialty/Research Focus:
Behavioral pharmacology; Neuropharmacology; Toxicology and Xenobiotics
Research Summary:
Research in my laboratory centers on the study of psychoactive drugs with special emphasis on nootropics and drugs of abuse.
In collaboration with Dr. Richard Rabin of this department, behavioral data are correlated with biochemical indices of drug action in an attempt to understand at the receptor level the effects in intact animals of psychoactive drugs. Behavioral data are obtained using the techniques of operant behavior with special emphasis on the phenomenon of drug-induced stimulus control. Current interests include the serotonergic basis for the actions of indoleamine and phenethylamine hallucinogens including LSD and [-]-DOM as well as their interactions with selective monoamine reuptake inhibitors such as fluoxetine [Prozac]. In the area of nootropics, recent studies have examined the effects of EGb 761, an extract of Ginkgo biloba; for these investigations, a delayed non-matching to position task in a radial
maze is employed. Currently, studies are in progress to assess the serotonergic basis for the cognitive effects of drugs of abuse including LSD and MDMA [Ecstasy].
Behavioral pharmacology of psychoactive drugs, including psychotherapeutic agents and drugs of abuse; mechanisms of action of hallucinogens.
Research in Dr. Jerrold Winter‘s laboratory seeks to understand the ways in which drugs alter behavior. Many chemicals are candidates for study but attention in the last few years has centered on hallucinogens such as LSD, phencyclidine, DOM, and ibogaine. Another area of major interest is age-related memory impairment and those natural materials,
including ginseng and gingko biloba, which are purported to influence that impairment. The behavioral effects of these drugs are studied in rats trained with the techniques of operant conditioning. Specific variables in use at the present time include drug-induced stimulus control, radial maze acquisition and performance, and conditioned place preference and
aversion.
In addition, Dr. Winter actively collaborates with Dr. Richard Rabin of the Department of Pharmacology and Toxicology in order to correlate behavioral effects with biochemical indices of action at the receptor level and with functional efficacies in second messenger systems.
