Current research in our 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 the majority of early onset familial AD cases, while elevated levels of Par-4 expression are associated with increased vulnerability of neurons to apoptosis. We have also identified AATF (apoptosis antagonizing transcription factor) as a Par-4 interacting neuroprotective protein, we are investigating if targeted delivery of small AATF core peptides across the blood-brain barrier translates into a viable therapy for neurodegeneration. Our studies involve the application of a variety of gene transfer, targeting and expression techniques, including those applied in vitro in cultured cells and in vivo in transgenic and/or knock-in 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. Research in our lab was supported by grants from National Institutes of Health (NIH/NINDS, NIH/NIDDK), The Alzheimer's Association, The ALS Association, The American Federation for Aging Research, OCAST, Harold Hamm Diabetes Center, and the Department of Physiology at OUHSC.
Work in Dr. Guo's lab has contributed to the 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 (PS-1 M146V) responsible for early-onset Alzheimer disease.
Dr. Guo was a regular member in the NIH CMND study section and he also participated in grant reviews in NDGB and other NIH study sections as ad hoc reviewers. He has also reviewed grant applications for other national, state, local, as well as international funding agencies. Dr. Guo also works as editors for several professional journals and reviews submitted manuscripts on a regular basis.
Dr. Guo participates in teaching and mentoring of medical, dental, PA, nursing, and graduate students in physiology, neuroscience, and pathology courses. His lectures covered the topics in cardiovascular, respiratory, renal, reproductive, and central and peripheral nervous system. As associate course director of the Human Physiology course at OUHSC, he also participates in curriculum development, teaching assessment, and other administrative responsibilities. Several postdocs and graduate students completed their research work in Dr. Guo’s lab and moved on to become faculty members, research scientists, or clinical doctors in other universities and institutions.
Education:
Senior Research Associate (January, 1998 - June 1999. Subject: Molecular Neuroscience) Sanders-Brown Research Center on Aging, The Alzheimer’s Disease Research Center (ADRC), and Department of Anatomy and Neurobiology, University of Kentucky, 800 S. Limestone St., Lexington, KY 40536-0230.
Postdoctoral Scholar (September, 1995 - January, 1998. Subject: Molecular Neuroscience) Sanders-Brown Research Center on Aging, The Alzheimer’s Disease Research Center (ADRC), and Department of Anatomy and Neurobiology, University of Kentucky, 800 S. Limestone St., Lexington, KY 40536-0230
Ph.D. (Aug, 1990 - July, 1993. Program: Neurology and Neurobiology): Department of Neurology, Postgraduate Medical School, 301 PLA General Hospital, 28 Fuxing Road, Beijing 100853
MS (Aug, 1984 - July, 1987. Program: Neurophysiology): Department of Physiology and Neurobiology, the Third Military Medical University, Shapingba District, 30 Gaotanyan Street, Chongqing 630038.
M.D. (Aug, 1979 - July, 1984. Program: Medicine): College of Medicine, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017
Clinical/Research Interests:
Specific areas of investigation in Dr. Guo’s lab include:
- Regulation of cell death and survival signaling pathways by Alzheimer’s presenilin mutations.
- Pro-apoptotic actions of Par-4 (Prostate Apoptosis Response-4) in experimental models of neurodegenerative disorders.
- Involvement of Par-4 in regulation of synaptic signaling and plasticity.
- Cytoprotective Actions of AATF (Apoptosis Antagonizing Transcription factor): An endogenous interaction partner and antagonist of Par-4 activity.
- Regulation of APP processing by Par-4 and AATF under apoptotic and necroptotic and conditions
- Roles of oxidative stress and intracellular calcium homeostasis in neurodegeneration.
- Par-4 and AATF in diabetic cardiovascular, renal, and retinal complications, and in acute renal failure induced by ischemia/reperfusion.
- Extrinsic pathways mediated by secreted AATF and Par-4 in diabetic nephropathy and ischemic vascular injury.
Funding:
Research in our lab was supported by grants from National Institutes of Health (NIH/NINDS, NIH/NIDDK), The Alzheimer's Association, The ALS Association, The American Federation for Aging Research, OCAST, Harold Hamm Diabetes Center. Current research work in the lab is supported by internal funding from the Department of Physiology at OUHSC.
Select Honors and Accomplishments:
- Award for Outstanding Achievement in Biomedical Research, Chinese Medical Association, Beijing, 1993.
- Investigator Initiated Research Award, The ALS Association, 2002.
- NEOUCOM Summer Research Fellowship Award, 2000, 2001, 2002.
- New Investigator Initiated Research Award, Alzheimer’s association, 2001.
- Investigator Initiated Research Award, Alzheimer’s association, 1999.
- Research Challenge Award, Northeastern Ohio Universities College of Medicine, 1999, 2000.
- Award for Outstanding Achievement in Biomedical Research, Chinese Medical Association, Beijing, 1993.
Select Publications:
Qing Guo, Jun Xie, and Chelsea J. Guo. Par-4 in Neuronal Death and Survival in Alzheimer’s Disease and Other Neurogenerative Diseases. In (Vivek. M. Rangnekar Eds) Tumor Suppressor Par-4: Role in Cancer and Other Diseases. Vol.2 Springer Nature. 2021; 215-245. https://link.springer.com/chapter/10.1007/978-3-030-80558-6_14
Jun Xie, and Qing Guo. Par-4 inhibits choline uptake by interacting with CHT1 and reducing its incorporation on the plasma membrane. J Biol Chem 2004; 279, 28266-28275. https://www.jbc.org/article/S0021-9258(20)73266-7/fulltext
Qing Guo, Lois Sebastian, Bryce Sopher, Miles W. Miller, Gordon W. Glazner, Carol B. Ware, George M. Martin, and Mark P. Mattson. Neurotrophic factors (ADNF and bFGF) interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation. Proc. Natl. Acad. Sci. USA. 1999; 96(7): 4125-4130 https://www.pnas.org/doi/10.1073/pnas.96.7.4125
Qing Guo, Weiming Fu, Jun Xie, Hong Luo, Stephen J. Sells, James W. Geddes, Vimala Bondada, Vivek M. Rangnekar and Mark P. Mattson. Par-4 is a new mediator of neuronal degeneration associated with the pathogenesis of Alzheimer’s disease. Nature Medicine 1998; August, 4(8): 957-962 https://www.nature.com/articles/nm0898-957