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
My research and practice focuses on developing, promoting, and evaluating effective means of pharmacology instruction at the undergraduate, graduate, professional, and interprofessional levels. Developing a competency-based curriculum in pharmacology for students at all levels, I have incorporated specific instructional methods into existing core courses that has, in effect, taken a sometimes intimidating subject like pharmacology and presented it to students in manageable ways. Studies of the effectiveness of these methods are conducted in collaboration with professional societies, including ASPET and its Division of Pharmacology Education. Specific instructional methods in the study include: patient case presentations by professional students utilizing rubric descriptors of performance quality and 360 feedback; Pharm Fridays throughout the second year medical curriculum incorporating organized lists of pertinent drugs to recognize, student-oriented learning objectives, pharmacology study guides focusing on essential therapeutics, their indications, mechanisms of action, adverse drug reactions, and drug interactions; active participation clicker sessions with relevant board-style pharmacology questions; development of performance-based pharmacology questions within the multidisciplinary objective structured clinical exam (OSCE) taken by all DDS candidates; and video presentations demonstrating pertinent pharmacology topics such as medical sedation, use of emergency drugs in the clinic, and safe and effective means for pain management with interviews of clinical experts. These and other instructional methods in the study are highly rated by students and proven effective by outcomes on standardized exams. For the last several years, I have been co-director of the endocrine-reproductive biology module for second-year medical students. As an ongoing means to improve pharmacology instruction, I coordinated the recent survey of pharmacology instruction in the medical curriculum, assessing adequacy of pharmacology learning objectives, utility of various instructional methods, coverage of USMLE Step 1 pharmacology expectations, and incorporated mechanisms to improve instruction and medical student preparation in pharmacology. Other recent advancements include the launching of an online pre-professional undergraduate pharmacology course with all presentations fully accessible to persons with disabilities.
Endocrinology, Diabetes and Metabolism; Neurodegenerative disorders; Pathophysiology; Endocrinology; Molecular Basis of Disease
Dr. Browne’s research is focused primarily on the clinical biochemistry of oxidative stress (OS) in human health and disease. Specifically, his research focuses on mechanisms of oxidative lipid damage and the antioxidant roles of high-density lipoproteins (HDL. This research includes pure biomarker method development and validation employing primarily high pressure liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) along with collaborative clinical studies of the role of oxidative stress in cancer, infertility and women’s health, and neurological disease. Current studies on-going in Dr. Browne’s laboratory include investigations of the role of HDL and PON1 in embryo morphology outcomes during in vitro fertilization (IVF), a study of the role of oxysterols in Multiple Sclerosis disease progression and investigations of the role of bioactive lipid mediators in response to air pollution.
Endocrinology, Diabetes and Metabolism; Psychiatry; Behavioral pharmacology; Endocrinology; Neurobiology
My research is broadly concerned with studies of the biology of affective disorders and the development of biological markers and clinical laboratory tests for major depressive disorder. Hormonal modulation of brain and behavior with the emphasis on gonadal hormones and the hypothalamic-pituitary-adrenal system neurotransmitter and their metabolites. A second area of work involves studies of premenstrual changes and menopause and hormone related changes in mood and behavior in women. Studies include: influence of hormonal replacement therapy; the development of clinical and diagnostic procedures; the association between gonadal hormones and other hormones, their change over time and clinical pathology, and the relationship between affective symptomatology during periods of change in the woman‘s life cycle and affective disorders.
Pathophysiology; Cytoskeleton and cell motility; Endocrinology; Eukaryotic Pathogenesis; Gene Expression; Molecular Basis of Disease; Molecular and Cellular Biology; Molecular genetics; Protein Function and Structure; Regulation of metabolism; Transcription and Translation
In my laboratory, we are interested in structural components of the cell, their role in establishing and regulating cellular functions, and how this regulation translates into physiological consequences in health and disease. We have two major focus areas: 1) The role of cytoskeletal elements in prostate cancer development and progression and 2) The role of nucleoskeletal elements in establishing and maintaining nuclear structure and function. 1) The majority of death from cancer is caused by metastasis, the spreading of cancer cells from the site of a primary tumor to other body parts. We use a combination of biochemical, cell biological, physiological, and translational approaches to elucidate the mechanisms that are involved in the acquisition of metastatic phenotypes. Specifically, we focus on the role that myosins play in this process. We are also interested in how dietary fats can contribute to the development of metastatic phenotypes in prostate cancer cells. 2) Aberrations in nuclear structure and dynamics are the underlying cause of diseases ranging from cancer to premature aging. We are interested in the role of nuclear actin and myosins in regulating dynamic nuclear processes such as nucleolar assembly and functions in health and disease.
Apoptosis and cell death; Endocrinology; Molecular and Cellular Biology; Gene Expression; Regulation of metabolism; Signal Transduction
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.
Apoptosis and cell death; Bioinformatics; Endocrinology; Gene Expression; Gene therapy; Genomics and proteomics; Immunology; Molecular Basis of Disease; Molecular and Cellular Biology; Neurobiology; RNA; Viral Pathogenesis
Dr. Mahajan has established herself as an investigator in the area of neuropathogenesis of HIV-1 in the context of drug abuse. She has established 2D and 3D Blood Brain Barrier (BBB) models, that allow studying mechanisms of BBB pathophysiology, examine BBB integrity and evaluate permeability of neurotherapeutics across the BBB. She investigates the role of a unique key signaling molecule in the dopaminergic pathway called DARPP-32, that impacts drug addiction, depression and other neurological disorders. Her focus has always been on collaborative, interdisciplinary partnerships between various Departments within UB that include the Institute of Lasers, Photonics and Biophotonics, Research Institute of Addiction, Dept of Computer Science and Engineering, Dept of Pharmaceutical sciences, Dept of Oral Biology and the Department of Bioengineering and also multiinstitutional collaborations with University of Rochester Medical Center and SUNY Albany. This inclusive strategy has facilitated the emergence of a robust, innovative clinical translational research program that continues to grow steadily. Dr Mahajan has obtained independent research funding from NIDA, NSF iCorp, Pharmaceuticals like Pfizer, Shire, Global- CRDF, US- Fulbright and other Private Foundations such as Dr. Louis Skalrow Memorial trust. Dr. Mahajan is Director of Research of the Division of Allergy, Immunology & Rheumatology. She supervises the research training of the Allergy fellows, Medical residents, graduate and undergraduate students. Dr. Mahajan has presented her research work at National and International conferences and was an invited speaker at several seminars and colloquiums. She has authored over 108 publications in several top quality peer reviewed journals and has thus demonstrated a high level of scholarly productivity. She is a reviewer and an adhoc member of the editorial board of several journals in her field. The following is a brief synopsis of her research interests. HIV neuropathogenesis in the context of drug abuse: We proposed that Opiates act as co-factors in the pathogenesis of HIV-1 infections by directly suppressing immune functions of the host through interactions with mu-opioid receptors on lymphocytes. Exacerbation of HIV encephalopathy (HIVE) is observed with opiate abuse. The mechanisms underlying HIVE are currently undetermined however, they likely to include the generation of endogenous neurotoxins combined, perhaps synergistically, with bioreactive HIV-1 envelope proteins. We believe that these proposed mechanisms may work through a common signal transduction mechanism activating dopamine D1 receptors in the nucleus accumbens of the brain. Opiate abuse by HIV-1 infected subjects may exacerbate the progression of HIVE as a consequence of the combined effects of HIV-1 induced neurotoxins plus opiate induced increases in the D1 receptor activation. We hypothesize that the dopaminergic signaling pathway is the central molecular mechanism that integrates the neuropathogenic activities of both HIV-1 infections and the abuse of opiate drugs. In this context our investigation is focused on the DARPP-32 signalling pathway. Addictive drugs act on the dopaminergic system of the brain and perturb the function of the dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32 kD (DARPP-32). DARPP-32 is critical to the pathogenesis of drug addiction by modulating both transcriptional and post-translational events in different regions of the brain. DARPP-32 is localized within neurons containing dopamine receptors and is a potent inhibitor of another key molecule in the dopaminergic signaling pathway, protein phosphatase 1 (PP-1). We propose that the sustained silencing of DARPP-32 gene expression using specific siRNA delivered to the brain is an innovative approach for the treatment of drug addiction. The specific challenge of the proposed project is the non-invasive delivery of biologically stable, therapeutic siRNA molecules to target cells within the brain. We are developing biocompatible nanoparticles to both protect DARPP-32 specific siRNA against degradation and deliver it from the systemic circulation across the BBB to specific dopaminergic neurons in the brain of patients with opiate addictions. BBB Research: While examining neuropathogenesis of HIV, we became interested in the role of the blood-brain barrier (BBB) in HIV neuropathogenesis with the objective of developing therapeutic interventions to prevent and limit the progression of HIV associated neurological disease. The blood-brain barrier is an intricate cellular system composed of vascular endothelial cells and perivascular astrocytes that restrict the passage of molecules between the blood stream and the brain parenchyma. The in-vitro BBB models allow examining permeability of virus, effects of drugs of abuse on BBB permeability, mechanisms of BBB transport, and tight junction modulation. Our goal remains to determine the impact of current and potential CNS antiretrovirals, psychopharmacologic, and other medications on the integrity of the BBB in HIV associated neurological disorder and other neurodegenerative diseases. Additionally, we also investigate mechanisms that underlie drugs of abuse induced neuronal apoptosis. Systems biology approach: We expanded our investigation to include functional genomic/proteomic NGS analyses that allowed characterization of gene/ protein modulation in response to a drug stimulus or under a specific disease condition. We developed an expertise in these large-scale genomic and proteomic studies and the genomic studies helped identify key genes that underlie molecular mechanisms in drug addiction, HIV diseases progression, and allowed examination of the interplay of genes and environmental factors. The proteomic studies confirmed the presence of specific proteins that regulate key biological processes in drug addiction and HIV diseases progression. Recently, We have expanded my research program to include microbiome analyses and incorporated the utility of the computational drug discovery platform (CANDO) model that allows studying interaction between protein structures from microbiome genomes and determine the interactions that occur between them and small molecules (drugs and human/bacterial metabolites that are already a part of or continue to be added to the CANDO library. Using the CANDO Platform we are able to do the hierarchical fragment-based docking with dynamics between those compounds/drugs and the microbiome proteins/proteomes to determine which ones of the drugs and metabolites will work most efficaciously in patients using specific drugs. NanoMedicine: We have developed a strong program in nanomedicine and have initiated several interdisciplinary clinical translational research focused collaborations that include 1) Nanotechnology based delivery systems to examine antitretroviral transport across the BBB; 2) Nanotherapeutics using siRNA/Plasmid delivery to specific regions in the brain to target various genes of interest specifically those pertaining to the dopaminergic pathway that result in the modulation of behavioral response which we observed in animal models of addiction/depression; 3) Biodistribution studies of various nanotherapeutic formulations using PET small animal imaging. Additionally, We are also focused on exploring epigenetic mechanisms that under drug addiction and mechanisms that underlie oxidative stress in neurodegenerative diseases.
Endocrinology; Molecular Basis of Disease; Neurobiology; Regulation of metabolism; Inherited Metabolic Disorders; Protein Function and Structure; Transgenic organisms
One research goal is to investigate the structure-function relationships and regulation of the human pyruvate dehydrogenase complex (PDC). We investigate the catalytic mechanism of the pyruvate dehydrogenase (PDH) component and its interactions with the dihydrolipoamide acetyltransferase (E2) component of PDC. We also determine the loci of interactions between PDH kinases (four PDK isoenzymes) and the lipoyl domains of E2. Using a PDC-knockout mouse line we investigate the importance of glucose metabolism as a source of energy for fetal development as well as the role of PDC in glucose-stimulated insulin secretion by pancreatic beta cells. Another research goal is to investigate diet-induced metabolic programming during early life. We investigate (i) the effects of an altered nutrition during the immediate postnatal life on development of adult-onset obesity and (ii) the effects of maternal obesity on fetal programming. Current research focuses on the role of the hypothalamic signaling pathways in rodents with diet-induced obesity and also in the progeny of obese mothers.