Olivier Joseph

Congenital lipodystrophy is a rare disease characterized by the inability to create adipocytes, cells that store excess fat. The absence of mature adipocytes in adipose tissue causes fat to be deposited on other parts of the body like the muscle and liver, which leads to insulin resistance. Together, elevated amounts of fat in the blood and resistance to insulin, the hormone that regulates blood glucose, leave those affected with a higher risk of developing Type 2 Diabetes (T2D) and cardiovascular disease (CVD). Identifying specific genes responsible for adipocyte dysfunctions that cause insulin resistance can provide the framework for drug development for patients with lipodystrophy and comorbid diseases. Using a high throughput human adipocyte differentiation assay, we conducted a pilot loss of function screen of 100 genes in order to identify novel regulators of adipocyte differentiation. We conducted a follow-up investigation on one of the genes to validate its effect on adipocyte differentiation. Using the CRISPR/Cas9 genome editing system, we created a preadipocyte line deficient in this gene and stimulated adipogenesis to characterize the extent to which this gene regulates adipocyte differentiation.

 

PROJECT: Examining adipocyte differentiation to discover novel insulin resistance genes

Mentors: Amit Majithia, Laeya Najmi and Robert Rice, Program in Metabolism and Medical and Population Genetics

 

Oliver L. Joseph

This summer’s SRPG experience was transformative. Looking back on it now, I could never have imagined that I would be walking away with the knowledge, experience, new skills, networks, and friends that I have now. I conducted science with global implications. How many undergrads can say that? I learned to better think critically and communicate with clarity. Initially, the expectations my mentor set for me seemed impossibly high. Now, I’ve exceeded expectations and am looking for the next challenge to push myself even further.