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David Shackelford, Ph.D.

Contact Information:

Work Phone Number:

310-567-3835

Office Address:

10833 Le Conte Avenue
Los Angeles, CA 90095
UNITED STATES
AR-255

UNITED STATES

Work Email Address:

dshackelford@mednet.ucla.edu

Member, CTSI


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

Publications:

  Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. Jan 28 2011;331(6016):456-461., , ; .
  Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. Aug 2009;9(8):563-575., , ; .
  Shackelford DB, Vasquez DS, Corbeil J, et al. mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome. Proc Natl Acad Sci U S A. Jul 7 2009;106(27):11137-11142., , ; .
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