Archana Unnikrishnan, PhD

Biography

Dr. Unnikrishnan received her doctorate in Nutrition and Food Science from Wayne State University and pursued aging research training at the University of Oklahoma. Currently Dr. Unnikrishnan has a cross faculty appointment with the department of Biochemistry and Molecular Biology and Harold Hamm Diabetes Center. Dr. Unnikrishnan’s research focuses on various aspects of Aging, (1) the effect of short-term dietary restriction (DR) on aging and insulin sensitivity, (2) the effect of short-term DR on intestinal stem cell aging, (3) the effect of short-term dietary restriction on DNA methylation, and (4) the role played by DNA methylation in short-term dietary restriction mediated metabolic/cellular memory. Her preliminary work shows that short-term DR improves glucose tolerance within days of starting the restriction reaching significance by 10 days and has a metabolic memory i.e., the effect of DR on insulin sensitivity and glucoregulation persists even when DR is discontinued. To understand the mechanism behind the metabolic memory she is studying DNA methylation and is currently using a novel technology to measure the genome-wide patterns of 5mCG and 5hmCG in specific sequences of mice fed ad libitum or a DR diet. As a proof of concept data from the methylation work shows that DR alters DNA methylation status of the cis-acting region of the promoter of Nts1 gene which persists even when DR is discontinued. This ongoing study is the first study to determine the role played by DNA methylation in the short-term DR mediated cellular/metabolic memory.
Her research also focuses on characterizing the effect of short-term and life-long DR on DNA methylation in intestinal stem cells (ISC) and delineate the functional outcome of these methylation changes with respect to intestinal stem cell regeneration, and integrity using organoids. Recent data from her lab shows that ISCs from old mice have limited proliferation activity and form few if any organoids in vitro (a surrogate for a fully functional crypt) and that ISCs isolated from old mice on life-long DR show an improved ability to form organoids. Most importantly, her lab recently found that ISCs from old mice fed DR for only a few months resulted in a dramatic increase in ability of the ISCs to form organoids. This is the first evidence that DR administrated late in life can rescue the loss in ISC function that occurs with age. She also aims to determine if DNA methylation plays a role in the DR mediated changes in the expression of genes involved in stem cell function, insulin sensitivity and age-related diseases. This research holds promise to understand how modifying genes sensitive to nutrition can pattern metabolism for a lifetime.

Email

Archana-Unnikrishnan@ouhsc.edu

Publications

Research Interests:

• Aging
• Dietary Restriction
• Epigenetics
• Insulin Sensitivity
• Microbiome
• Intestinal Stem Cell Biology

Additional Profiles:

• Department Webpage
• OUHSC Research Profile