OUHSC Department of Physiology

Dr. Qing Guo received his M.D. degree in medicine in 1984, M.S degree in physiology in 1987, and Ph.D. in neurobiology in 1993. He pursued postdoctoral research in molecular biology of apoptosis under Professor Mark P. Mattson in Sanders-Brown Center on Aging at the University of Kentucky before he joined faculty in the Department of Neurobiology and Pharmacology at Northeastern Ohio Universities College of Medicine (NEOUCOM) in 1999. In 2003, Dr. Guo became an Associate Professor in the Department of Physiology at the University of Oklahoma Health Sciences Center.

RESEARCH WORK IN DR. GUO'S GROUP:
Dr. Guo's research has for many years been concerned with the development of cellular and transgenic approaches to the study of cell death in health and disease. Many diseases in humans are associated with dysregulation of cell death and survival. Excessive cell death, via apoptosis, necrosis, or other forms of cell death, leads to lost of functional cells and is linked to diseases in various systems related to ischemia, myocardioinfarction, stroke, neurodegenerative disorders (including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and spinal muscular atrophy), renal failure, osteoporosis, and complications associated with diabetes and HIV infection. On the other hand, aberrant repression of cell death may be causally linked to tumorigenesis (cancers), autoimmune diseases, and productive viral infection.

Current research in Dr. Guo's laboratory centers on some of the fundamental questions in the life and death of cells in a variety of organ systems and diseases. First, we examine how specific genetic mutations and cell death proteins regulate intracellular pathways that control neuronal life and death associated with neurodegenerative diseases. In this respect, we are specifically looking at the pathogenic mechanisms of presenilin-1 (PS-1) mutations and pro-apoptotic actions of prostate apoptosis response-4 (Par-4) protein in several transgenic mouse models of Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). Mutations in presenilins-1 are responsible for majority of early onset familial AD cases, while elevated levels of Par-4 expression are associated with increased vulnerability of neurons to apoptosis. Work in Dr. Guo’s lab has contributed to our understanding of a number of mechanisms for dementia of Alzheimer’s type caused by the heritable alterations of genetic information in presenilin proteins, which included the investigation of neuronal cell death process in the first mouse "knock-in" model of a naturally occurring presenilin-1 mutation responsible for an early-onset form of Alzheimer disease. We also study the mechanisms by which specific proteins regulate cholinergic neurotransmission and synaptic function. Secondly, we have expanded our study to include the mechanisms by which specific cell death and/or survival proteins regulate apoptosis in models of human diseases outside the central nervous system. Specifically, we are looking at how aberrant regulation of the apoptotic machinery is involved in pathological conditions such as acute renal failure induced by ischemia/reperfusion, diabetes, cardiovascular problems, bone disease, and cancer. One of the factors we are currently working on is apoptosis antagonizing transcription factor (AATF), a novel leucine zipper protein that interacts directly with Par-4 and functions as an endogenous antagonist of Par-4 activity in many physiological and pathological settings. Our studies involve the application of a variety of gene transfer, targeting and expression techniques, including those in applied in vitro in cultured cells and in vivo in transgenic and/or knockin mouse models. The overall goal of our research is to understand the molecular and cellular mechanisms of cell death in human diseases, and to identify novel therapeutic strategies using genetic and/or pharmacological manipulations. Specific areas of investigation include the following:
• Regulation of apoptotic and cell survival signaling pathways by presenilin mutations
• Pro-apoptotic actions of Par-4 in experimental models of neurodegenerative disorders (Alzheimer’s disease and ALS)
• Involvement of Par-4 in regulation of synaptic signaling and plasticity
• AATF as an endogenous interaction partner and antagonist of Par-4 activity
• Regulation of APP processing by Par-4 and AATF under apoptotic and non-apoptotic conditions
• Roles of oxidative stress and intracellular calcium homeostasis in neurodegeneration
• Par-4, AATF and pathogenesis of acute renal failure induced by ischemia/reperfusion.
• Cell death and visceral dysfunction

Dr. Guo's group has published extensively in the field, many of them in high impact jurnals. Research in his lab has been supported by grants from National Institutes of Health (NIH/NINDS, NIH/NIDDK), The Alzheimer’s Association, The ALS Association, American Federation for Aging Research, Northeastern Ohio Universities College of Medicine (NEOUCOM) Research Challenge Funds, and Startup Funds from NEOUCOM and the University of Oklahoma Health Sciences Center (OUHSC).

Dr. Guo serves on NIH study sections and reviews manuscrits for a variety of profesional journals. Dr. Guo has been a regular member of the NIH Cellular and Molecular Neurodegneration (CMND) Study Section since July, 2008. He also served on NIH NDGB (Neurodegenration and Glial Cell Biology) study section and reviewed grant proposals for Alzheimer’s Association, Israel Science Foundation, Georgian-U.S. Bilateral Grants Program, Science Foundation Ireland, an Health Foundation (PHF) and College of Medicine Alumni Association (COMAA) at OUHSC.

DR.GUO AS A TEACHER AND MENTOR FOR MEDICAL AND GRADUATE STUDENTS:
A high degree of success by medical and graduate students rarely comes without active mentorship. Dr. Guo's teaching experience began in 1984, and since then he has gathered excellent teaching skills through extensive interaction with students in medical and graduate schools. This has exposed him to students of different academic, ethnic and economical backgrounds, with diverse career goals and personal interests. He enjoys teaching and believes that excellence in teaching is as critical to science as excellence in research. His goal as a teacher is to facilitate and enrich student learning through motivation, discussions, insightful ideas, and responding to students’ questions and feedbacks.

Dr. Guo has taught many topics including lectures and lab sessions in Medical Neuroscience, Functional Neuroanatomy, Medical Physiology, Medical Problems, Cell Death in Physiology and Disease, Mechanisms of Aging, Reproduction and Women’s Health, and Journal Clubs. He has been the course director for Integrative Physiology, a core course for graduate students in Graduate Programs in Biomedical Sciences (GPiBS) here at OUHSC. He served as Chair of graduate programs in Physiology at OUHSC. He has also had the pleasure of mentoring seven PhD students in his lab. Beyond his own laboratory, he served on many PhD dissertation committees, covering campuses of Northeastern Ohio Universities College of Medicine and Pharmacy (NEOUCOM), OUHSC and Oklahoma Medical Research Foundation (OMRF).

Contact Dr. Guo: e-mail: qing-guo@ouhsc.edu Phone: (405) 271-8001 ext. 56268