Understanding the role of Metabolic Regulator SIRT5 in Acute Lymphoblastic Leukemia
Nataly Cruz-Rodriguez
PhDVersiti Blood Center of Wisconsin
Project Term: July 1, 2024 - June 30, 2026
SIRT5 is a master regulator of central energy metabolism. The survival and growth of Acute Myeloid Leukemia (AML) cells depend on SIRT5. I will employ genetic SIRT5 disruption and small molecule inhibitors to target SIRT5 in Acute Lymphoblastic Leukemia (ALL) cells and primary samples. This study aims to 1) determine the effects of SIRT5 inhibition on ALL in vitro and in vivo, and 2) identify SIRT5-regulated pathways and mechanisms underlying SIRT5 dependency in T-ALL.
Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children, and it also occurs in adults over 60. Kids have a good chance of surviving with the current treatments, but adults have a lower success rate. CAR-T cell therapy helps some patients, but not those with relapsed/refractory T-ALL. In addition, kids who survive ALL often face health issues later due to therapy. To improve ALL treatments, we're looking at how a protein called SIRT5 affects the metabolism of T-ALL cells. We know that restricting energy can stop cancer development, but in B-ALL, certain mutations remove this brake, leading to cancer. We have studied SIRT5 in Acute Myeloid Leukemia (AML), another type of leukemia, and now I think it might also be important in T-ALL.
I have two goals:
- Understand how blocking SIRT5 affects T-ALL in the lab and in animals, and
- Find out which pathways and mechanisms depend on SIRT5 in T-ALL. If SIRT5 turns out to be crucial, we might be able to use drugs to target it in T-ALL for better treatments.