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.
Apoptosis and cell death; Cell growth, differentiation and development; Cytoskeleton and cell motility; Immunology; Signal Transduction; Stem Cells
My independent research at The University at Buffalo focuses on targeting the mammary gland microenvironment by evaluating cellular and tissue responses during specific developmental windows of mammary gland remodeling including puberty, the period of hormonal withdrawal during estrous cycling, or post-lactational involution. My choice to focus on discrete times of development for chemopreventive intervention, rather than long-term (and often life-time) intervention, represents a unique approach of short-term exposure at critical points of mammary gland development. Our goal is to allow women to bypass the need for lifelong compliance to a chemopreventive diet or drug regimen in order to attain lifelong protection against breast cancer. Developmentally targeted dietary interventions being investigated in our lab include continuous administration of oral contraceptives, dietary exposure to conjugated linoleic acid, and ethanol.
Behavioral pharmacology; Neurobiology; Neuropharmacology; Regulation of metabolism; Signal Transduction
Catecholamines such as dopamine and norepinephrine in the brain play important roles in a wide range of disparate physiological and behavioral processes such as reward, stress, sleep-wake cycle, attention and memory. The catecholamines are also well known for their treatment of neural disorders and many other diseases. Therefore, the examination of the catecholamines is of great importance not only in pharmaceutical formulations but also for diagnostic and clinical processes. The role and contribution of catecholaminergic innervation in the limbic system to biological functions and behavior are still poorly understood, however, due to the complicated functional heterogeneity, the small size of the limbic brain nuclei. In vivo and in vitro electrochemical measurement at microelectrodes has enabled direct monitoring of neuronal communication by chemical messengers in real time, which provides new insight into the way in which information is conveyed between neurons. Such information enables to study the basis for understanding the mechanisms that regulate it, the behavioral implications of the chemical messengers, and the factors regulate normal and altered chemical communication in various disease states (e.g. cardio vascular disease, degenerative nerve diseases, and drug addiction). My overall research focuses on two areas. Firstly, the design and implementation of development of new types of electrochemistry-based sensors and ancillary tools to monitor catecholamines and nonelectroactive neurochemicals in a chemically complex environment in the peripheral and central nervous systems of test animals. Secondly, application of the newly developed analytical techniques or existing methodologies for real-time monitoring of the neurochemicals i) to understand role of the neurochemicals in the brain in stress- and reward-related behaviors, ii) define and understand dysfunctions of the central and peripheral nervous systems in disease states by observing fundamental changes in neurochemical transmission in anesthetized and awakened animals.
My research for the last 25 years has focused on carbohydrate antigens that are important in cancer and in infectious disease (bacterial, viruses and parasites). These structures play important roles in the growth, adhesion and spread of cancer cells and bacteria and viruses. Immune responses to these structures can therefore be an effective mechanism to decrease disease. The anti-carbohydrate immune response is usually T cell independent, more difficult to develop and less in magnitude than the immune response to proteins.My long-term goals involve using information obtained about carbohydrates of related structures to manipulate the anti-carbohydrate immune response to improve clinical outcome. This work has involved use of synthetic oligosaccharides conjugated to bovine serum albumin as antigens, the use of structurally related synthetic oligosaccharides in inhibition studies, the use of antibody to carbohydrates in immunotherapy and immunolocalization of cancer, the use of genetic analysis of genes related to carbohydrate synthesis and adhesion, bacterial vaccine stability assays and bacteria rapid diagnosis assay development. The immunochemical aspects of this work were performed to determine the immunodominant regions of the sugars and the effects of small structural changes in the inhibitory oligosaccharides on the immunologic reaction. I have been involved in research concerning the immune response to carbohydrate antigens since 1984, through experience gained while a post-doctoral fellow at Roswell Park Cancer Institute (RPCI), gaining clinical diagnostic experience with Dr. T. Ming Chu, (the discoverer of Prostate Specific Antigen for diagnosis) and then carbohydrate experience with Dr. Khushi Matta (Carbohydrate synthetic chemist). Since that time, I have been involved in the development of monoclonal and polyclonal antibodies to defined saccharides as diagnostic markers or as vaccine candidates in both bacterial and cancer research. My laboratory, RPCI based for the first 9 years, and now at UB for the last 13 years, has had an emphasis on tumor associated carbohydrate antigens, and recently has been involved in 2 patent applications, “Use of anti-TF antibody to block metastasis of TF- antigen bearing tumors” (K R Olson, principle inventor of JAA-F11 monoclonal antibody), and “Carbohydrate Antigen-Nanoparticle Conjugates and Methods for Inhibiting Metastasis in Cancer” (K R Olson, co-inventor). Thomsen-Friedenreich antigen (TF-Ag) is a tumor associated antigen that is exposed in many types of carcinoma cells including breast, prostate, colon, and bladder.