Genes & Human Disease Research Program, MS 57
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-3139
Fax: (405) 271-3045
The central focus of our research is regulation of the genome through epigenetic mechanisms including how stimuli (e.g., parabiosis, viral infection, diet, early life adversity) cause persistent epigenome changes that effect cellular function throughout life. We use a combination of transgenic mouse approaches (NuTRAP), next generation sequencing, and bioinformatic methods to understand epigenetic processes within specific CNS cell populations (microglia, astrocytes, neurons). Similarly, we examine accumulation of mutations and deletions to the mitochondrial genome with aging and diabetes; pairing these measurements to assessments of mitochondrial function. Our scientific advances over the past decade in aging research have been: a) identifying that the majority of age-related CNS epigenomic changes are sexually divergent; b) disproving the genomic hypomethylation with aging hypothesis; c) determining that, from a molecular neurobiology perspective, cognitive decline is associated with activation of specific pathways (e.g., Nogo signaling) and is not simply a more aged phenotype; d) periods of poor glycemic control cause CNS epigenomic changes that do not normalize with re-establishment of normoglycemia; e) development of a series of novel epigenomic sequencing tools. Our long-term goal is to mechanistically alter the epigenome to maintain healthy brain function and prevent the neuroinflammation with aging.