Department and Program Faculty
Faculty of Pharmacology and the Program in Biomolecular Pharmacology
A listing of faculty with appointments in Pharmacology and faculty participants in the Biomolecular Pharmacology Program follows. Faculty with a primary or secondary appointment in the Department of Pharmacology and Experimental Therapeutics have their names marked with two asterisks (**). Faculty members who are participating in the NIGMS Training Grant have their names marked with one asterisk (*). Faculty who are in the department, but who are not accepting students are indicated with a dagger (†). Links lead to a detailed description of research interests, a list of representative publications and a picture, where available.
**David H. Farb, Ph.D., Professor and Chair of Pharmacology.
Research Interests: Abnormal activation of amino acid receptors has been implicated in the etiology of psychiatric disorders such as anxiety, depression, schizophrenia, as well as of convulsive disorders. Impaired cognition is a common symptom of these and other neurological disorders, including neurodegenerative disorders, and the development of cognitive enhancers would provide significant symptomatic relief for many patients. Ongoing studies provide a strong foundation for constructing models of steroid hormone interactions with excitatory and inhibitory amino acid receptors in the brain and spinal cord. This knowledge may lead to new strategies for the treatment of psychiatric and cognitive disorders. The role of neuroactive steroids and small molecule modulators in the control of GABA, glycine, and glutamate (NMDA and non-NMDA) receptors is being investigated using a multidisciplinary approach that includes the techniques of molecular biology, cell biology, mouse transgenics, patch-clamp neurophysiology, and in vivo chronically implanted high density electrode recordings of neuronal ensembles in freely moving rats and transgenic mice.
*Carmela Abraham, Ph.D. Professor of Biochemistry.
Research Interests: Dr. Abraham’s laboratory studies the mechanisms of normal brain aging and the etiology of Alzheimer’s disease (AD). Dr. Abraham is studying the function of the amyloid precursor protein (APP) and a novel protease involved in the degradation of the amyloid beta peptide (A-ß) in order to understand the etiology of AD and design possible treatments. Dr. Abraham’s laboratory also investigates normal human brain aging and uses the rhesus monkey as a model. Specifically, they are interested in the expression of gene products that could contribute to the destruction of myelin. They have found, using microarray analyses, that the anti-aging gene, Klotho, is downregulated in the aging brain and are now characterizing the role of Klotho and ways to elevate its expression.
*Karen N. Allen, Ph.D., Associate Professor of Chemistry.
Research Interests: Research in the Allen group is concerned with diverse aspects of protein structure, function, and ligand design. The lab employs a multidisciplinary approach involving state-of-the-art X-ray crystallography and spectroscopy, molecular modeling, enzymology, and molecular biology to address fundamental problems at the interface of enzymology and structural biology. Current projects focus on the aldolase isozymes, the dolichol pathway enzymes, and the haloacid dehalogenase superfamily.
*Salomon Amar, D.M.D., Ph.D., Professor of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine.
Research Interests: Dr. Amar devotes approximately 70% of his time to research in cell and molecular biology. His interests focus on the control of TNF-α and other cytokine gene expression in inflammatory diseases; the role of infection in cardiovascular disease and obesity; the application of “omics” approaches to mapping of signaling pathways; and the characterization of cells and extracellular matrix macromolecules in wound healing and tissue regeneration.
*David Atkinson, Ph.D. Professor of Physiology and Biophysics
Research Interests: Dr. Atkinson’s research efforts aim to provide detailed structural and conformational information on the molecular organization and interactions of lipids and proteins in plasma lipoproteins. The primary approaches use the techniques of X-ray/neutron scattering, protein crystallography, structural electron microscopy/image processing, nuclear magnetic resonance, calorimetry, circular dichroism, and molecular modeling to probe the structure and physical properties of lipoproteins, lipoprotein apoproteins and lipid/apoprotein reassembled model systems.
*Irving J. Bigio, Ph.D. Professor of Biomedical Engineering, Electrical & Computer Engineering, Physics
Research Interests: The focus of Dr. Bigio’s research is the development of minimally-invasive diagnostics and therapeutics based on optical and photonic technologies. Ongoing projects include: 1) Development of fiber-optic probes to perform spectroscopic measurements on tissue in vivo and noninvasively to instantly detect early cancer and other pathologies in situ. 2) Fiber-optic probes to measure drug concentrations in tissue, local spatial profiles and local kinetics, noninvasively and in real time. 3) Sensors to monitor the response of tumors to specific treatments. 4) Optical methods for noninvasive imaging of neuronal activation and brain function.
*Victoria M. Bolotina, Ph.D. Associate Professor of Medicine and Physiology.
Research Interests: The research focus is on ion channels and mechanisms of calcium signaling in a variety of cell types. Methodologies include patch clamp, high resolution confocal and deconvolution imaging, and molecular and biochemical techniques (including knock-out mouse models) to study single channels and whole-cell currents, regulation of membrane potential, intracellular calcium, vascular tone, and expression, activity and localization of several major determinants in calcium signaling cascades. The large part of her recent research is devoted to studying store-operated channels and capacitative calcium entry pathway in vascular smooth muscle cells, cardiac myocytes, platelets, T-lymphocytes, astrocytes and beta cells.
†Charles Cantor, Ph.D. Professor of Biomedical Engineering and Pharmacology (leave of absence), Chief Scientific Officer at Sequenom, Inc.
Research Interests: Dr. Cantor’s major research effort is the development of novel methods for detection and modulation of cells that express specific nucleic acid sequences. His laboratory is using split fluorescent protein complementation to view specific transcripts in living cells. Such methods may also allow novel in vivo imaging modalities. Similar approaches are being explored to alter the properties of specific cells in living organisms. It is possible that such methods will mature into extremely specific targeted intervention methods with high therapeutic indices.
**Jiang-Fan Chen, M.D., Ph.D., Associate Professor of Neurology and Pharmacology.
Dr. Chen’s research focuses on the neurobiology of adenosine and the A2A adenosine receptor and the role they may play in the development and treatment of neuropsychiatric disorders. Dr. Chen has developed an A2A receptor knockout mouse model and couples this genetic approach with pharmacological manipulation to explore the pathophysiological role of A2A receptors in animal and cellular models of neuropsychiatric disorders. The knowledge derived from these studies may provide the neurobiological basis for rational development of A2A receptor agents as treatment strategies for neuropsychological disorders, ranging from Parkinson’s disease to drug addiction.
†Aram Chobanian, M.D., President Emeritus of the University, Boston University; University Professor; Professor of Medicine and Pharmacology, John I. Sandson Distinguished Professor of Health Sciences, Boston University School of Medicine
*Dominic A. Ciraulo, M.D., Professor and Chairman of Psychiatry.
Dr. Ciraulo’s research interests focus on addiction psychopharmacology. He is the Principal Investigator of the National Institute on Drug Abuse and The BUSM Medication Development for Stimulants Center, and the Principal Investigator on grants from the National Institute on Alcohol Abuse and Alcoholism that study the role of medications and psychosocial therapies in the treatment of alcoholism. His research also examines the relationship between animal and human models for screening of medications to treat addiction. The medication development program incorporates the latest neuroimaging technologies in collaboration with the Brain Imaging Center at Boston University School of Medicine.
*Richard A. Cohen, M.D. Professor of Medicine.
Research Interests: The research programs of the Vascular Biology Unit are directed towards an integrative molecular understanding of abnormal vascular endothelial and smooth muscle cell function in diseased blood vessels and its contribution to abnormal vascular reactivity, hypertrophy, inflammation, and atherogenesis. Research projects focus on the mechanisms by which vascular risk factors associated with diabetes mellitus, hypercholesterolemia, and hypertension lead to abnormal production of vasoactive factors from the endothelium and also how they alter the smooth muscle cell response. These factors include nitric oxide, prostanoids, oxygen–derived free radicals, cytokines, and growth factors. Experimental approaches employ cell physiology of cultured endothelial and smooth muscle cells with measurements of intracellular calcium and oxygen–derived free radicals, coupled with studies of molecular signaling. The influence of altered production of endothelial factors and signaling cascades on inflammatory responses and cell adhesion is studied as it applies to the development of atherosclerotic lesions, particularly in diabetes. Post-translational modification by tyrosine nitration and thiol oxidation of proteins studied by immuno/affinity labeling and mass spectrometry has been shown to alter the function of endothelial cell nitric oxide synthase, sarcoplasmic reticulum ATPase, endothelial nitric oxide synthase, p21ras, manganese superoxide dismutase, and prostacyclin synthase. S-glutathiolation has been demonstrated as a reversible thiol modification that that modulates cell signaling. Proteomic approaches are being used to screen proteins for oxidant modifications that occur as physiological mechanisms or are a consequence of excess reactive nitrogen species.
**Pietro Cottone, Ph.D., Assistant Professor Department of Pharmacology,
Dr. Cottone is co-director of the Laboratory of Addictive Disorders. Dr. Cottone’s research interests focus on the neurobiological substrates of motivated behaviors including feeding and addiction. The major goal of Dr. Cottone’s research is identifying the biological bases of and potential treatments for obesity and eating disorders. Current studies concern the role of stress in compulsive eating and palatable food dependence. Areas of focused research include the investigation of the neurobiological bases of stress-related disorders such as anxiety and depression. Dr. Cottone’s studies are carried out on environmental and genetic animal models, using behavioral, biochemical, and molecular approaches.
*Charles Delisi, Ph.D. Metcalf Professor of Science and Engineering and Dean Emeritus, College of Engineering
Research Interests: The Biomolecular Systems Laboratory develops and applies computational/mathematical methods, and high throughput experimental methods, to analyze changes in gene and protein expression profiles of cells in response to various endogenous and exogenous signals. In collaboration with the Fraunhofer Center for Manufacturing Innovation, and the Departments of Chemistry and Physics, Dr. DeLisi is developing and applying new DNA and peptide microarray technologies for fingerprinting the complete molecular state of a cell. Examples include the response to ligands (drugs, toxins, hormones), and changes that occur as normal cells mature, differentiate, and progress toward disease. The long-range goal is to relate expression patterns to pathways, pathways to networks, and networks to function.
**Gerald Denis, Ph.D. Assistant Professor of Pharmacology and Medicine, Cancer Research Center.
Research Interests: Our laboratory is investigating transcriptional control of the cell cycle and how the cell cycle is perturbed in cancer. We are specifically interested in the double bromodomain protein Brd2, which is a transcriptional co-activator of the cyclin A gene. Levels of cyclin A correlate closely with DNA synthesis during the S phase of the cell cycle; S phase entry is often earlier in tumor cells. Brd2 binds to acetylated histones through its bromodomains, associates with the SWI/SNF chromatin remodeling complex, then recruits transcription factors and co-activators to cyclin A promoter chromatin to regulate transcription. In transgenic mice that constitutively express Brd2 in B cells, cyclin A is upregulated and the cell cycle is destabilized, leading to an aggressive non-Hodgkin’s lymphoma. Genome-wide transcriptional profiling of this malignancy revealed that its molecular signature most closely resembles the ‘activated B cell’ form of non-Hodgkin’s lymphoma in humans. Therefore, this mouse represents a new model for diffuse large B cell lymphoma; we now suspect that it recapitulates some aspects of Richter’s transformation of B cell chronic lymphocytic leukemia into a much more aggressive type of B cell lymphoma that is often fatal, and which is poorly understood in human cases. We are identifying new drug targets and developing original pharmacologic approaches for its treatment. We have recently reconstituted the murine immune system with hematopoietic stem cells transduced with lentiviruses for Brd2 overexpression or shRNA knockdown, and learned that Brd2 expression causes a dramatic expansion of the B cell compartment in vivo and B cell hypersensitivity to mitogenic stimulation in vitro, nicely recapitulating the transgenic model. On the other hand, Brd2 knockdown completely blocks lymphoid development, suggesting that this factor plays a crucial and fundamental role in normal immune biology and the processes of adaptive immunity.
**Howard Eichenbaum, Ph.D. Professor of Psychology and Pharmacology. Director, Center for Memory and Brain; Director, Cognitive Neurobiology Laboratory; Director, Center for Neuroscience.
Research Interests: Dr. Eichenbaum’s major research goals are elucidation of the function of the hippocampus and the functional organization of the medial temporal lobe memory system. Specific projects include: 1.) Hippocampal and cortical coding, a study to assess the functional correlates of single neuron and neuronal ensemble activity in the cortex and hippocampus of rats performing memory tasks, 2.) Hippocampal lesions or localized NMDA receptor KO and memory, projects that will characterize the roles of the hippocampus and parahippocampal region in rats and mice, 3.) The effect of aging on hippocampal behavioral physiology and memory performance in rats, 4.) A study to test the hypothesis that schizophrenia is associated with decreased function of corticolimbic NMDA receptors.
*Lindsay A. Farrer, Ph.D. Chief, Genetics Program; Professor, Depts. of Medicine, Neurology, and Genetics and Genomics, Boston University School of Medicine and Depts. of Epidemiology and Biostatistics, Boston University School of Public Health.
Dr. Farrer’s research investigates genetic risk factors in familial neurodegenerative and other chronic diseases. In collaboration with other laboratories worldwide, his group has localized genes causing rare and common disorders including Alzheimer disease (AD), age-related macular degeneration, dependence on illicit substances (cocaine, opiates, nicotine, and alcohol), complications of sickle cell disease, Wilson disease, Machado-Joseph disease, Waardenburg syndrome, asthma, and metabolic syndrome. Many of these projects are collaborative and multi disciplinary efforts aimed at linking human genetic variation to biological mechanisms and developing novel therapeutic targets.
**Jane Freedman, Ph.D. Professor of Medicine and Pharmacology.
Research Interests: Coronary artery plaque rupture leads to platelet-dependent thrombosis and myocardial infarction. The major research initiatives in this laboratory include an emphasis in the molecular regulation of pathways contributing to thrombosis, vascular disease, and how these factors contribute to acute coronary syndromes. The main topics include: platelet signaling pathways, molecular regulation of platelet nitric oxide and reactive oxygen species, and the role of inflammation in thrombosis.
**Terrell T. Gibbs, Ph.D. Associate Professor of Pharmacology.
Research Interests: Dr. Gibbs’ research efforts focus on the pharmacology of neurotransmitters and neuromodulators, and on mechanisms of modulation and regulation of neurotransmitter receptor function, including up-regulation, down-regulation, desensitization, and tolerance. Current studies concern the acute and chronic effects of modulators of amino acid receptor function, including benzodiazepines, barbiturates, and steroids. Computational and electrophysiological methods are used to evaluate thermodynamically plausible models for receptor function. Methodologies include the use of radioligand and/or electrophysiological techniques of studying receptor function.
*Robert C. Green, M.D., M.P.H., Professor of Neurology, Genetics and Epidemiology.
Dr. Green’s research interests are in early and preclinical detection, treatment and prevention of Alzheimer’s disease. He is the Clinical Core director and Associate Director for the Boston University Alzheimer Disease Core Center. Dr. Green is also a co-Principal Investigator on Boston University’s NIH-funded MIRAGE (Multi-Institutional Research in Alzheimer’s Genetic Epidemiology) Study, a consultant on the NIH-funded Cache County Memory and Aging Study and is the Boston site director of the NIH-funded ADAPT (Alzheimer’s Disease Anti-Inflammatory Prevention Trial) Study, one of the first large-scale intervention trials to prevent the development of Alzheimer’s disease in at-risk family members. Dr. Green is also Principal Investigator and Director of the REVEAL (Risk Evaluation and Education for Alzheimer’s disease) Study, a multi-center project funded by the National Human Genome Research Institute and the National Institute on Aging to develop genetic risk assessment strategies for individuals at risk for Alzheimer’s disease.
*Mark W. Grinstaff, Ph.D. Professor of Biomedical Engineering, Chemistry and Ophthalmology.
Research Interests: The Grinstaff group pursues highly interdisciplinary research in the areas of biomedical engineering and macromolecular chemistry. In one current research project, his group is designing, synthesizing, and characterizing novel dendrimers, termed “biodendrimers,” for tissue engineering and biotechnological applications. These novel biomaterials are being evaluated for the repair of corneal lacerations, for the delivery of anti-cancer drugs, for the delivery of DNA, and as temporary biodegradable scaffolds for cartilage repair. In a second project, his group is creating novel polymeric coatings termed “interfacial biomaterials” that control biology on plastic, metal, and ceramic surfaces.
*James A. Hamilton, Ph.D. Professor of Physiology and Biophysics.
Research Interests: Dr. Hamilton’s laboratory is developing and applying novel physical approaches to study of obesity, metabolic syndrome, and cardiovascular disease. 13C NMR methods pioneered in his laboratory have been used to describe the interactions of fatty acids and drugs with binding sites on albumin, and new studies are currently correlating important details predicted by NMR with recent x-ray crystal structure. His laboratory has determined the complete solution structure of several intracellular fatty acid binding proteins (FABP) by multi-dimensional NMR and is studying the molecular details of ligand binding to FABP. New fluorescence approaches have been developed to characterize the diffusion of fatty acids into adipocytes and evaluate the effects of drugs and inhibitors on fatty acid uptake. A newer focus of research is on imaging methodologies, mainly magnetic resonance imaging (MRI), of fat tissue and atherosclerosis. These studies extend from animal model systems (mouse and rabbit) to humans. The work emphasizes interactions of different disciplines on translation of basic biophysics to human disease aspects.
*Michael Hasselmo, Ph.D. Professor of Psychology.
Dr. Hasselmo’s laboratory research concerns cortical dynamics of memory-guided behavior, including effects of neuromodulatory receptors and the role of theta rhythm oscillations in cortical memory. Neurophysiological techniques are used to analyze effects of modulators on synaptic and neuronal activity in cortical circuits in the rat, and computational modeling is used to link this physiological data to behavior. Experiments using multiple single-unit recording in behavioral tasks are designed to test predictions of the computational models. Areas of focused research include episodic memory function and theta rhythm dynamics in hippocampal formation. Research addresses physiological effects relevant to Alzheimer’s disease, schizophrenia and depression.
**Alan Herbert, MB.ChB., Ph.D. Associate Professor of Pharmacology and Neurology.
Dr. Herbert’s laboratory has just completed a whole genome scan of families from a community-based population that involved typing 100,000 single nucleotide polymorphisms per individual and identified a common variant that increases risk of obesity. The closest gene INSIG2 is involved in the regulation of fatty acid synthesis. Another variant affecting a gene in the same pathway, ACACA, is associated with leanness. Dr. Herbert is in the process of initiating a high-throughput screen of candidate drugs for these genes as targets, using a chemical library available through the Center for Methodologies and Library Development at Boston University. Analysis of other traits is also underway, potentially providing insight into pathways of addiction and genes that predict successful neurological aging.
**Gary B. Kaplan, M.D. Professor of Psychiatry and Pharmacology.
Research Interests: In addiction, cognitive and motivational brain regions are responsive to salient environmental and contextual drug cues that serve as triggers for continued vulnerability to relapse. Our research examines drug reward and craving responses to drug-associated cues and contexts in animal models. Extinction is a form of learning that can reduce the rewarding properties associated with drug cues and contexts but such learning occurs over long periods of time. Our translational research examines the neural mechanisms underlying extinction of conditioned drug reward and drug priming induced reacquisition of conditioned drug preferences. To study long term changes in synaptic plasticity in extinction of conditioned drug reward, we examine regulation of transcription factors is relevant limbic and cortical circuitry. To enhance extinction learning, we utilize translational pharmacological approaches using N-methyl-D-aspartate (NMDA) glutamate and aminobutyric acid (GABA) receptor agonists and examine behavioral and neurochemical effects of these agents. By understanding the behavioral and the neural mechanisms for enhancement of drug related reward extinction, we hope to block craving and relapse in clinical populations.
*Catherine Klapperich, Ph.D. Assistant Professor, Biomedical Engineering and Manufacturing Engineering
The Biomedical Microdevices and Microenvironments Laboratory (BMML) is focused on the design and engineering of manufacturable, disposable microfluidic systems for low-cost point-of-care molecular diagnostics. We are currently working on devices for the detection of infectious diarrhea, influenza and MRSA. They are also studying the interactions between cells and synthetic microenvironments. Specifically, we are interested in building culture systems in vitro that mechanically mimic the physiological environment. These synthetic microenvironments are intended for use in diagnostics, high throughput drug screening, and to enable previously impossible basic science studies. Currently we have projects aimed at recapitulating the microenvironments of the breast, cochlea and neural tissue.
**Conan Kornetsky, Ph.D. Professor of Psychiatry and Pharmacology.
Research Interests: Dr. Kornetsky’s research is directed toward the determination of neuronal mechanisms involved in the behavioral effects of drugs. Much of this research is focused on the brain’s motivational systems that are directly related to the rewarding effects associated with abused psychomotor stimulants and opioids. Methodologies include stereotaxic surgery for implanting intracerebral stimulating electrodes and/or cannulae directly into specific brain sites, psychophysical determination of thresholds for various types of intracerebral electrical stimulation, intravenous drug self-administration in rats, quantitative determination of cerebral metabolic rates in specific brain areas using 2-[14C] deoxyglucose, and brain-stimulation reward in knockout mouse models.
†Vidhya Kumaresan, Ph.D. Research Assistant Professor of Pharmacology
Overall research objective is to study neuronal activity-dependent plasticity and its relevance for brain disorders. The current focus of Dr. Kumaresan’s research is to understand the neurobiological bases of addiction to psychostimulants. Recidivism to drug abuse is a major hurdle in the successful treatment of addiction. Illicit drug use usurps neural circuits involved in survival enhancing behaviors. The goal is to elucidate the cellular and molecular underpinnings of drug-induced enduring neural plasticity in these circuits using a combination of behavioral, cellular and molecular approaches. In particular, Dr. Kumaresan employs a novel approach of using cell-permeable peptides that disrupt protein-protein interactions in vivo in order to study ongoing behavior. These approaches are expected to lead to successful treatment of relapse precipitated by drug re-exposure, drug-associated cues and stress. Knowledge gained from these studies will also be applicable to the treatment of other brain dysfunctions involving persistent memories such as PTSD.
**Susan E. Leeman, Ph.D. Professor of Pharmacology.
Research Interests: Dr. Leeman’s work focuses on the two peptides, substance P (SP) and neurotensin, which were isolated and chemically defined in her laboratory. Projects that are currently underway include: 1. the role of glycosylation of the NK1 receptor on its signal transduction pathways, 2. the roles of SP in several models of inflammation in the gastrointestinal tract, including post-surgical cell adhesion formation, and the effect of non-peptide SP antagonists. 3. the role of LITAF, a newly described transcription factor participating in TNF alpha synthesis in macrophages obtained from inflamed colonic tissue.
*Adam Lerner, M.D. Associate Professor of Medicine and Pathology.
Research Interests: Dr. Lerner studies the potential use of cyclic nucleotide phosphodiesterase inhibitors as novel therapeutic agents for the treatment of human lymphoid malignancies. He has found that PDE4 inhibitors not only induce apoptosis in primary human chronic lymphocytic leukemia (B-CLL) cells but also augment the ability of glucocorticoids to induce B-CLL apoptosis, and he is elucidating the mechanisms of these phenomena. He also studies AND-34, an SH2 domain-containing protein that he has shown binds to the focal adhesion protein p130Cas. His current work focuses on understanding the signaling pathway by which AND-34 over-expression induces anti-estrogen resistance in human breast cancer cells.
*John R. Murphy, Ph.D. Professor of Medicine
Research interests: The research interests of Dr. Murphy’s group includes the design, expression, and characterization of diphtheria toxin-related cytokine fusion proteins, the molecular basis of diphtheria tox gene regulation, and the molecular mechanisms by which large hydrophilic proteins are transported into eukaryotic cells. They have shown that the delivery of the diphtheria toxin catalytic domain from the lumen of early endosomes to the cytosol of target cells requires the participation of Hsp90, thioredoxin reductase, and other cytosolic translocation factors. In addition, they have recently demonstrated the molecular mechanisms for formation of the metal ion dependent active form of the diphtheria toxin repressor, DtxR. Studies are in progress to identify small peptides activators as a unique approach to antimicrobial agent development.
**Susan Perrine, M.D. Associate Professor of Pediatrics, Medicine, and Pharmacology; Director of the Hemoglobinopathy-Thalassemia Research Unit
**Philip Podrid, M.D., Professor of Medicine and Professor of Pharmacology.
**John A. Porco, Jr., Ph.D. Professor of Chemistry and Pharmacology.
Research Interests: Research activities in the Porco group (people.bu.edu/porcogrp) involve the development of new methodologies for organic synthesis and their application to synthesis of complex natural products and analogues. Targets for synthesis include pharmacologically active compounds where the preparation of structural variants will allow investigation of key regulatory interactions with biomolecules. Dr. Porco and colleagues have also established the Boston University Center for Chemical Methodology and Library Development (CMLD-BU, cmld.bu.edu) for development of methodologies for the stereocontrolled synthesis of complex molecule libraries for biological screening.
*Tyrone M. Porter, Ph.D., Assistant Professor of Biomedical Engineering.
Due to its relatively low cost, portability, and beamforming capabilities, ultrasound is an ideal tool for noninvasive evaluation and treatment of a broad range of medical ailments, including vascular occlusions and cancer. Research in the Medical Acoustics Laboratory (MedAL), led by Dr. Tyrone Porter, is focused on the design and fabrication of ultrasound technology to improve upon the diagnosis and treatment of debilitating diseases. This includes the development of targeted ultrasound contrast agents for molecular imaging applications and nano-sized vesicles that release drugs when exposed to acoustic fields. The combination of diagnostic and therapeutic technology may potentially lead to noninvasive image-guided treatment of diseases.
*Katya Ravid, Ph.D., Professor of Biochemistry.
Research Interests: The cells of all blood lineages arise from pluripotent hematopoietic stem cells that reside in the marrow. The bone marrow also contains stem cells of other lineages, including fat, vascular etc. Our research is focused on two interrelated projects that bear on mechanisms associated with the development of blood and vascular pathologies: (1) Studies in the lab center on molecular mechanisms involved in cell cycle control during the development of bone marrow megakaryocytes into platelets, a process that includes cellular polyploidization prior to platelet fragmentation. We also identified mechanisms of polyploidy in vascular smooth muscle cells, and found that the degree of polyploidy serves as an excellent biomarker for aging; (2) Ongoing studies explore the role of vascular and bone marrow cell (progenitors and mature) adenosine receptors in vascular regeneration during injury or atherosclerosis. Transgenic and knockout mouse models are used to assist in exploring mechanisms in vivo.
**Karen Reed, Ph.D., Associate Research Professor of Surgery and Associate Professor of Pharmacology.
Dr. Reed’s research focuses on two areas medically and economically relevant to gastroenterology. One area involves the molecular and cellular characterization of proinflammatory regulators of intra-abdominal adhesion formation while the second area focuses on the etiology of inflammatory bowel disease (IBD). In the area of adhesion formation we have demonstrated that a specific substance P receptor antagonist reduces post-surgical adhesion formation and that this response involves tissue plasminogen activator (tPA), matrix metalloproteinases and oxidative stress. In similar studies we have also shown that HMG-CoA reductase inhibitors reduce adhesion formation. These studies have led to several publications and awards including a paper in the Proceedings of the National Academy of Sciences and a “Best Poster Presentation” award at the international meeting of the Peritoneal Access Society held in Belgium. I am also extremely interested in understanding the pathogenesis of IBD. I have been involved in research to characterize the involvement of the transcription factor NFkB, as well as its upstream activators and downstream mediators, in intestinal inflammation in the rat. I have also contributed to research investigating the role of substance P as well as the transcriptional regulator, LITAF, in intestinal inflammation.
*Douglas L. Rosene, Ph.D. Professor of Anatomy and Neurobiology.
Research Interests: Dr. Rosene’s research interests center on identifying the neurobiological basis of normal learning and memory and related cognitive functions in the normal brain and the disruption of these processes in neurodegenerative diseases, localized neurological damage such as stroke and by stressors such as malnutrition. To accomplish this, multidisciplinary studies of animal models use combinations of behavioral, neurohistochemical, neurophysiological and neuroanatomical techniques to study these cognitive functions. Studies use the rhesus monkey as a model of normal aging, of cerebrovascular disease and neurological damage as well as a rat model of prenatal malnutrition.
**Shelley J. Russek, Ph.D. Professor of Pharmacology.
Research Interests: The research of Dr. Russek’s laboratory is focused on gene regulatory mechanisms responsible for the expression and function of neurotransmitter receptors in the normal and diseased brain. Using genomic strategies that include chromatin immunoprecipitation, DNA and receptor pull-down, single cell imaging, and delivery of viral vectors into animals, the laboratory uses the interface between in vitro and in vivo models to test mechanisms of disease and to develop novel genetic therapies for disorders such as epilepsy, autism, and Rett’s syndrome.
**Valentina Sabino, Ph.D., Assistant Professor, Department of Pharmacology,
Dr. Sabino is co-director of the Laboratory of Addictive Disorders. Dr. Sabino is currently researching the neurobiology of addiction and stress-related disorders. Studies on addiction aim to understand the neurobiological substrates of alcohol abuse and dependence, by exploring the role of central neurochemical systems in excessive alcohol drinking. She is working toward the development of new therapeutic agents to alleviate alcohol addiction. Animal models for excessive drinking are studied in order to identify compounds for potential clinical development. Research is also conducted on the neurobiology of stress-related disorders such as anxiety and depression. The laboratory uses environmental and genetic animal models of disease, with a multidisciplinary approach to understand the neurobiology of psychiatric disorders and to develop novel therapies.
**Scott Schaus, Ph.D. Associate Professor of Chemistry and Pharmacology.
Research Interests: Dr. Schaus’s research group concentrates on the development of novel technologies to investigate cellular processes such as cell cycle regulation, cell proliferation, and intracellular signaling. Genomic transcription profiling of both model organisms and mammalian cells is employed to validate drug targets and cellular response mechanisms. Current projects include the investigation of protein synthesis and amino acid biosynthesis regulatory mechanisms, MAPK cellular signaling pathways, and the development of microarray technologies.
†Cassandra Smith, Ph.D. Professor of Biomedical Engineering, Biology, and Director, Pharmacology, Molecular Biotechnology Research Laboratory
†Temple F. Smith, Ph.D. Professor of Biomedical Engineering and Research Professor of Pharmacology, Director, Pharmacology, BioMolecular Engineering Resource Center
*Jean-Jacques Soghomonian, Ph.D. Associate Professor of Anatomy and Neurobiology.
Research Interests: The laboratory focuses on the functional neuroanatomy of the basal ganglia and the neurobiological basis of motor control, sensori-motor integration, and learning. His particular interest is the mechanisms of regulation of GABAergic neurons in the basal ganglia in the normal brain and in experimental models of Parkinson’s disease and the neuronal basis of l-DOPA-induced dyskinesias. Techniques include microdialysis, quantitative in situ hybridization histochemistry, immunohistochemistry, quantitative computerized image analysis and assessment of behavioral activity.
*Remco Spanjaard, Ph.D. Associate Professor of Otolaryngology and Biochemistry; Research Assistant Professor of Biochemistry
Research Interests: Dr. Spanjaard’s research addresses genetic mechanisms involved in several types of neoplasms. In one project he is studying a new class of RNA coactivator in the pseudouridine synthase (PUS) family that stimulates nuclear receptor-dependent gene regulation via a novel posttranscriptional modification of a highly unusual other RNA co-activator. In a second project he is studying a recently identified orphan member of the TNF receptor superfamily (TROY), which is uniquely expressed on primary and metastatic melanomas. In a third project, he is investigating the role of a p53-regulated, pro-apoptotic DNA damage response gene in breast cancer and chemotherapy resistance. Finally, he is investigating the identification and characterization of new tumor markers in head and neck squamous cell carcinoma that may serve as diagnostic/prognostic indicators and novel therapeutic targets.
**Thomas D. Tullius, Ph.D. Professor of Chemistry and Pharmacology.
Research Interests: The Tullius laboratory focuses on developing and applying new chemical probe methods for determining the structure of DNA, RNA, and DNA-protein complexes in solution. His group introduced the use of the hydroxyl radical as a high-resolution chemical footprinting reagent for nucleic acids. They are using deuterium kinetic isotope experiments to obtain detailed information on the chemical mechanism of oxidative damage to DNA and RNA induced by the hydroxyl radical. A major project is developing a database of hydroxyl radical cleavage patterns of DNA to make structural maps of regions of the human genome involved in the regulation of gene expression and elucidate the rules by which DNA sequence is translated into three-dimensional structure.
*Carol T. Walsh, Ph.D. Professor of Pharmacology.
Research Interests: Dr. Walsh’s research has included studies in gastrointestinal pharmacology, the toxicology of metal compounds, and pharmacokinetics. Her current interests include: 1.) the effect of transporter proteins on the pharmacokinetics of drugs and toxic substances, 2.) the impact of genetic variants on drug absorption, distribution and elimination, and 3.) the pharmacokinetics of protein therapeutics. Currently, Dr. Walsh is not conducting laboratory research, does not serve as a dissertation mentor, and is involved in this training program in an administrative capacity as well as through service on qualifying and dissertation committees. (Note: not accepting students)
*Kenneth Walsh, Ph.D. Professor of Medicine and Director, Whitaker Cardiovascular Institute.
Research Interests: Research in the Walsh laboratory has been focused in three areas. The major project investigates the signaling- and transcriptional-regulatory mechanisms that control both normal and pathological tissue growth in the cardiovascular system. Many of these studies involve analyses of the PI3-kinase/Akt/GSK/Forkhead signaling axis. This pathway is of critical importance in the regulation of organ growth and body size. Signaling through this pathway controls cellular enlargement (hypertrophy), cell death (apoptosis), and blood vessel recruitment and growth (angiogenesis). The second project investigates the role of the immune system in vascular disease. The formation of atherosclerotic lesions involves inflammatory cell interactions within the endothelium and subsequent extravasation into the vessel wall. Accelerated atherosclerosis is a critical factor contributing to the stroke and coronary heart disease that is a major cause of death among young women with systemic lupus erythematosus. The third project analyzes the actions of adiponectin on cardiovascular tissues. It is now recognized that adipose tissue functions as an endocrine organ and that obesity contributes to cardiovascular and metabolic disorders through an imbalance of cytokines. Adiponectin is an adipocyte-derived cytokine that is down-regulated in obese individuals. We have found that adiponectin has beneficial actions on the cardiovascular system by directly acting on the heart and blood vessels.
*David Waxman, Ph.D. Professor Biology and Medicine.
Research Interests: Humans, like other mammals, are exposed to a large number of toxic foreign chemicals, many of which are lipophilic and have a tendency to persist in fatty tissues. In response to this environmental challenge, mammals have evolved a large number of genes which encode cytochromes P450 and other enzymes that oxygenate lipophilic foreign compounds. Expression of these genes is controlled by a complex array of molecular regulatory circuits that respond to varying physiological conditions and changes in hormonal and environmental stimuli. In addition to metabolizing foreign chemicals, P450 enzymes hydroxylate physiological substrates, such as steroid hormones, arachidonic acid and cholesterol, which both compete with drug and other foreign chemical substrates and can regulate P450 metabolism through the modulation of P450 gene expression.
A major goal of our laboratory is to elucidate these metabolic processes at both the biochemical level and the molecular regulatory level. One of our research projects involves the regulation of liver P450 gene expression by the temporal pattern of pituitary growth hormone (GH) release. Other ongoing studies concern the regulation of these enzymes and their genes by factors such as thyroid hormone, circadian rhythms and non-genotoxic carcinogens classified as peroxisome proliferators. A second important goal of our laboratory is to identify ways through which our understanding of P450 biochemistry and gene regulation may be applied to improve human health. These efforts are exemplified by our development of cytochrome P450 as a model for cancer gene therapy using drug-susceptibility genes. P450 genes have great promise for applications designed to enhance the sensitivity of tumor cells to cancer chemotherapeutic drugs.
**Benjamin Wolozin, M.D., Ph.D., Professor of Pharmacology and Neurology
Research Interests: Dr. Wolozin’s research investigates the pathophysiology of neurodegenerative diseases. Research on Parkinson’s Disease focuses on the interaction between genetic factors implicated in this disease and environmental factors. His studies utilize cell culture, mammalian brain slice culture and transgenic lines of C. elegans, and results are then investigated further in transgenic/knockout mice and in human brain samples or cell lines from patients. His projects are also focused on identifying pharmacological strategies for Parkinson’s disease. The research on Alzheimer’s disease focuses on the interaction between the proteins that produce beta-amyloid and the genes that regulate cholesterol metabolism. Finally, Dr. Wolozin has an active epidemiological research program that examines the effects of FDA-approved medications on the incidence and progression of both Alzheimer’s and Parkinson’s disease.
*Joyce Y. Wong, Ph.D. Associate Professor of Biomedical Engineering.
Research Interests: Dr. Wong’s main research interest is in the development of new biomaterials that interact with living cells in novel ways. She is interested in questions relating to biocompatibility and control of cellular behavior at the cell-material interface for drug delivery and tissue engineering applications. Her approach includes direct measurement of physicochemical interactions between biological molecules and model biomembrane systems. Dr. Wong’s research uses a combination of approaches from materials science and engineering, polymer science and polymer physics, colloid and surface science, cell culture, and biophysics.
**Zhigang Xie, Ph.D. Assistant Professor Departments of Neurosurgery and Pharmacology.
Research Interests: Neural stem and/or progenitor cells (NSPCs) are promising cell sources for treating brain injury and degeneration. In addition, abnormal proliferation of NSPCs has also been linked to brain development disorders and brain tumors. Dr. Xie’s research interests include: (1) role of the centrosome in the proliferation of NSPCs during mammalian brain development; (2) regulation of NSPC proliferation by genes that are linked to human brain development disorders; (3) mechanisms underlying the proliferation and migration of NSPC-like stem cells in brain tumors.
