David Shackelford, Ph.D.

Office Address:
10833 Le Conte Avenue
Los Angeles, CA 90095 AR-255

Member, CTSI, Cell & Developmental Biology GPB Home Area, I3T Theme
Associate Adjunct Professor, Pulmonary and Critical Care Medicine

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.


A selected list of publications:

Wei Wei, Shi Qihui, Remacle Francoise, Qin Lidong, Shackelford David B, Shin Young Shik, Mischel Paul S, Levine R D, Heath James R   Hypoxia induces a phase transition within a kinase signaling network in cancer cells Proceedings of the National Academy of Sciences of the United States of America, 2013; 110(15): E1352-60.
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 Cancer cell, 2013; 23(2): 143-58.
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.), 2011; 331(6016): 456-61.
Shackelford David B, Shaw Reuben J   The LKB1-AMPK pathway: metabolism and growth control in tumour suppression Nature reviews. Cancer, 2009; 9(8): 563-75.
Shackelford David B, Vasquez Debbie S, Corbeil Jacqueline, Wu Shulin, Leblanc Mathias, Wu Chin-Lee, Vera David R, Shaw Reuben J   mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome Proceedings of the National Academy of Sciences of the United States of America, 2009; 106(27): 11137-42.
Gwinn Dana M, Shackelford David B, Egan Daniel F, Mihaylova Maria M, Mery Annabelle, Vasquez Debbie S, Turk Benjamin E, Shaw Reuben J   AMPK phosphorylation of raptor mediates a metabolic checkpoint Molecular cell, 2008; 30(2): 214-26.