Basic Science Research at the Reynolds has led to several seminal discoveries that support our overarching goal of developing “Strategies Toward Overcoming and Preventing Alzheimer’s” (STOP Alzheimers). These advances improve our understanding of risk factors such as the inheritance of specific gene alleles, aging and the wear and tear of time, obesity, and Type 2 diabetes… and how those factors favor development of neurodegenerative conditions ― including Down’s syndrome, Alzheimer’s and Parkinson’s disease, and vascular dementia.
Dr. Robert Reis’s studies of the genetics of aging and longevity have shown that genetic manipulation in a relatively simple model animal, C. elegans, can mimic neurodegenerative diseases and provides a quick and precise system for drug testing and defining mechanisms through which we can prevent or remove protein aggregates.
Dr. Sue Griffin’s discoveries, regarding the brain’s own immune cells (the small cells called glia) and how when activated by neuronal stress these cells set the stage for chronic neuroinflammation that acts to drive neurodegenerative events that give rise to protein aggregation and the characteristic neuropathological features of Down’s at middle age and Alzheimer’s and Parkinson’s in old age.
Dr. Steven Barger’s discovery of the seminal factor responsible for communication between stressed nerve cells and glia was the missing link that allowed us to discover previously unknown links between neuronal stress, glial activation with neuroinflammation, and failures in the nerve cell’s ability to dispose of or re-cycle proteins that instead form aggregates both outside and inside nerve cells and, in this way, create self-perpetuating cycles that culminate in neurodegeneration and dementia.
Dr. Gohar Azhar’s basic research interests include investigating transcriptional control of the aging heart and physiological evaluation of stress responses of the aging cardiovascular system.
Dr. Azhar was co-investigator on the NIH/NIA project titled “Transcription Regulation in the Aging Heart”. She is also P.l. on an STTR, titled, “Nutritional Therapy in Elderly with Heart Failure”, phase I on which has just been completed. In addition, she is collaborating on grants with investigators within the RIOA, across campus and at Nutrition Center at the Arkansas Children’s hospital. Dr. Azhar is collaborating nationally and is currently a co-investigator on the NIH-PCORI, collaborative multi-centered and multimodal, “Randomized Trial of a Multifactorial Fall Injury Prevention”.
Dr. Xiaomin Zhang is experienced in molecular biology, transgenesis and the genetic aspects of disease and aging. Dr. Zhang’s main research interests include the transcriptional regulation of gene expression during aging and senescence, and the mechanism underlying age-related changes in the heart and skeletal muscle. His is also interested in using molecular biology approaches to generate mouse models that resemble certain aspects of aging, and use these models to enhance our understanding the mechanism of aging and senescence.
Our newest research focuses on: how the most important genetic risk factor for development of Alzheimer’s disease, the APOE4 gene, interacts with specific DNA sequences to control the nerve cells’ ability to rid itself of unwanted or misfolded proteins; how environmental factors such as obesity and Type 2 diabetes act to deprive nerve cells of glucose and promote neuronal stress and loss; and, with our collaborator Dr. Peter Crooks, how specifically targeted brain-penetrant drugs decrease the levels of glial activation and production of neuroinflammatory proteins, prevent the formation of aggregates and destroy previously formed aggregates in C. elegans, and alter the effects of dietary changes that favor development of metabolic syndrome reminiscent of Type 2 diabetes.