Derek K. Cheng

Derek K. Cheng

Education:

B.S., M.S. Johns Hopkins University, 2011

Current Position:

8th Year MSTP

3rd Year Medical Student

Advisor:

David Tuveson, PhD, Cold Spring Harbor Laboratory

Graduate Program:

Genetics

Title

Proximity labeling of Oncogenic KRAS reveals novel protein complex interactions in pancreatic cancer

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Although activating mutations of the KRAS GTPase are the predominant dependency present in >90% of PDAC patients, targeting KRAS mutants directly has been challenging in PDAC. Similarly, strategies targeting known KRAS downstream effectors have had limited clinical success due to feedback mechanisms, alternate pathways and toxicity due to the targeting of normal tissues. Therefore, identifying additional functionally relevant KRAS interactions in PDAC may allow for a better understanding of feedback mechanisms and unveil new potential therapeutic targets. Here, we used proximity labelling to identify protein interactors of active KRAS in PDAC cells. Fusions of wildtype (BirA-KRAS4B), mutant (BirA-KRAS4BG12D) and non-transforming and cytosolic double mutant (BirA-KRAS4BG12D/C185S) KRAS with the BirA biotin ligase were expressed in murine PDAC cells. Mass spectrometry analysis revealed several known and novel candidate interactors of Ras which have been followed by function studies to determine their importance in pancreatic cancer.

Publications:
(pre-MSTP publications indicated with an *)

Cheng D, Tuveson D. Kras in Organoids. Cold Spring Harb Perspect Med. 2018;8(10):a031575. Published 2018 Oct 1. doi:10.1101/cshperspect.a031575

Kozlovskaya, V; Kharlampieva, E; Drachuk, E; Cheng, D and Tsukruk, VV. Responsive microcapsule reactors based on hydrogen-bonded tannic acid layer-by-layer assemblies Soft Matter, 2010,6, 3596-3608*

Farrar D, Ren K, Cheng D, Kim S, Moon W, Wilson WL, West JE, Yu SM. Permanent polarity and piezoelectricity of electrospun a-helical poly(a-amino acid) fibers.Adv Mater. 2011,23(34):3954-8*