David Shackelford, Ph.D.
Work Phone Number:
10833 Le Conte Avenue
Los Angeles, CA 90095
A Short Biography:
My research focuses on understanding how mutations in the AMPK and mTOR signaling pathways lead to altered metabolism and cell growth in human tumors. The AMPK-mTORC1 pathways lie at the intersection of oncogenic signaling and tumor metabolism. I am interested in understanding at a molecular level how loss of function and gain of function mutations in these signaling pathways alter growth signals and metabolic pathways to fuel tumor growth. The accelerated rate of growth in aggressive tumors creates a dependence on sustaining high metabolic rates, which also represents the tumor?s Achilles? heel. During my current work on lung and brain tumors I have focused on exploiting the tumor?s Achilles? heel, by disabling the machinery that drives tumor metabolism with drugs traditionally used to treat metabolic disease. Drugs such as biguanides are able to induce catastrophic metabolic stress and preferentially induce cell death in tumors. These studies open up the very real possibility of using therapeutics that were originally designed to treat metabolic disease as anti-cancer drugs.
Awards and Honors:
Recipient of UCLA KL2 Translational Science Award
Recipient of Ruth L. Kirschstein Postdoctoral Research Award
Shackelford David B, Abt Evan, Gerken Laurie, Vasquez Debbie S, Seki Atsuko, Leblanc Mathias, Wei Liu, Fishbein Michael C, Czernin Johannes, Mischel Paul S, Shaw Reuben J
LKB1 inactivation dictates therapeutic response of non-small cell lung
cancer to the metabolism drug phenformin.
Egan Daniel F, Shackelford David B, Mihaylova Maria M, Gelino Sara, Kohnz Rebecca A, Mair William, Vasquez Debbie S, Joshi Aashish, Gwinn Dana M, Taylor Rebecca, Asara John M, Fitzpatrick James, Dillin Andrew, Viollet Benoit, Kundu Mondira, Hansen Malene, Shaw Reuben J
Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase
connects energy sensing to mitophagy.
Science (New York, N.Y.),