Research in the Department of Biochemistry and Molecular Biology
Biochemistry is a discipline that serves as a foundation for studies of biological processes at the molecular level. Molecular biology, in its broadest sense, is the study of biological process at the molecular level. The research interests of the faculty cover areas that are relevant to disease processes that include cancer, neurodegenerative disease, hepatitis C, Parkinson’s disease, pulmonary disease, stress, and development of antimicrobial agents.
The department, comprising 10 faculty members, 11 Ph.D. graduate students and more than 20 research staff members, maintains a strong commitment to excellence in both research and teaching. While the group is about half the size of most medical biochemistry departments, NIH funding is close to the national average, with the total funding nearing $3 million annually.
Herewith is a summary of research in the Department of Biochemistry and Molecular Biology.
Arthur J. L. Cooper, Ph.D., professor, is studying transglutaminases, enzymes that catalyze covalent modifications of protein substrates. Aberrant transglutaminase activity is thought to contribute to neurodegenerative diseases. Selective transglutaminase inhibitors may therefore be clinically useful. Dr. Cooper is also studying the role of cysteine S-conjugate b-lyases, a type of enzyme involved in the bioactivation, or toxification, of endogenous and exogenous electrophiles. Such studies may be useful in devising methods to minimize the harmful effects of certain drugs.
Marietta Y.W.T. Lee, Ph.D., professor, studies the protein machinery required for DNA synthesis in human cells. Her laboratory is studying DNA polymerase delta, a key enzyme that has to replicate DNA with the utmost fidelity in order to avoid mutations. The enzyme also participates in the repair of DNA damaged by radiation and chemical agents. Her group is focused on the study of the human proteins with the goal of understanding their role in maintaining the integrity of the genome by the avoidance of mutations and the repair of mutations.
Ernest Y.C. Lee, Ph.D., professor describes his own research as involving the study of phosphoprotein phosphatases, which are important regulatory enzymes in a variety of cellular processes. He is currently studying a protein that inhibits protein phosphatase-1. This inhibitor is localized to the mitotic apparatus, and these studies are leading to the possibility that it plays a crucial role in mitotic regulation. Loss of such regulation leads to chromosomal aberrations that are commonly associated with tumor cells.
Susan C. Olson, Ph.D., associate professor, is conducting research into the peptide hormone angiotensin II (Ang II) as a stimulator of pulmonary endothelial cells to produce nitric oxide (NO), a potent vasodilator. Dr. Olson and her team hypothesize that this effect, which is in opposition to the well-established influence of Ang II as a vasoconstrictor, can be explained by signaling differences that result from the interaction of Ang II to discrete membrane receptors.
John T. Pinto, Ph.D., professor, explores mechanisms of action of naturally-occurring and synthetic organosulfur and organoselenium compounds and their ability to a) modify oxidation/reduction capacity in human cells, b) alter growth of human cancer cells by targeting redox sensitive transcription factors/signal proteins and c) regulate proliferative and/or apoptotic responses. Dr. Pinto’s lab also examines the attenuating effects of resveratrol, phytochemicals derived from red grapes, on vascular oxidative stress and inflammation in diabetes.
Esther L. Sabban, Ph.D., professor, is investigating the mechanisms that regulate neurotransmitters. Long-term abnormalities in catecholamine neurotransmission are involved in a number of prevalent diseases such as stress, cardiovascular disorders, Parkinson's disease and depression. Dr. Sabban's team is investigating how single and repeated stress, as well as exposure to nicotine, alter gene expression of these neurotransmitters in the periphery and in the central nervous system.
Yuk-Ching Tse-Dinh, Ph.D., professor, is exploring the structure, function and regulation of DNA topoisomerases, enzymes that modify the topological state of DNA. She is also trying to identify novel antibacterial compounds that target bacterial DNA topoisomerase I to combat multi-drug resistant bacterial pathogens. The long-term goal of Dr. Tse-Dinh's lab is to understand how DNA topology is regulated and how it affects biological functions.
Joseph M. Wu, Ph.D., professor, has focused his research on the mechanism of chemoprevention and cardioprotection by dietary and botanical agents, specifically resveratrol and several polyphenols isolated from botanical sources. His team is also actively purifying and identifying cellular targets of resveratrol and bioactive polyphenols obtained from plants. SiRNA knockdown approaches are used to determine the role of the identified targeting proteins of resveratrol in the prevention of prostate cancer and other malignant diseases. Since 2006, Dr. Wu's lab has also embarked on studies of a recently discovered synthetic purine called reversine, which has been found to be a potent aurora kinase B inhibitor with novel activity in controlling the mitotic chromosomal passenger complex checkpoint and in inducing mitotic catastrophe in leukemia, prostate, and breast cancer cells.
Zhongtao Zhang, Ph.D., assistant professor, is studying Parkinson’s disease, the second leading degenerative neurological illness that affects an estimated 1.5 million people is the US alone. His laboratory is studying the fundamental biochemical reactions that could cause this disease. He is studying some novel proteins that are involved in the pathogenesis of Parkinson’s disease, and the elucidation of their functions, may lead to novel treatment and prevention therapies.