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Rushika M. Perera, PhD

Research and Clinical Interests

Organelle dynamics and metabolic reprogramming in pancreatic cancer

How do cancer cells escape tightly controlled regulatory circuits that link their growth to extracellular signaling cues? An emerging theme in cancer biology is how, in addition to genetic alterations in signaling pathways (eg. MAPK and PI3K), cancer cells can hijack normal stress response pathways to overcome strict reliance on external nutrients for growth. Pancreatic adenocarcinoma (PDA) is the quintessence of an aggressive malignancy that thrives in nutrient poor, hypoxic environments, by systematically altering the core pathways for nutrient acquisition and utilization. These alterations include increased uptake of glucose and glutamine, along with constitutive activation of scavenging pathways that converge at the lysosome, namely autophagy (cellular self-catabolism) and macropinocytosis (bulk uptake of extracellular material).

In our lab we study the cancer-specific mechanisms of autophagy-lysosome activation, and how this organellar system contributes to metabolic reprogramming in PDA. We hypothesize that the functional interplay between enhanced cellular trafficking pathways and activation of gene programs that regulate organelle dynamics and function is an essential, previously unrecognized mechanism for tumor growth. Our studies using a combination of biochemistry, fluorescence imaging and proteomics in PDA cell lines, mouse models and primary patient derived cultures aims to provide insight into how fundamental cellular process are rewired in cancer while also identifying new nodes for anti-cancer therapy.

Selected Publications

  • Perera RM, Stoykova S, Nicolay BN, Ross K, Fitamant J, Boukhali M, Lengrand J, Deshpande V, Selig MK, Ferrone CR, Settleman J, Stephanopoulos G, Dyson NJ, Zoncu R, Ramaswamy S, Haas W, Bardeesy N. Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism. Nature, 2015 Aug 20; 524(7565):361-5.
  • Perera RM*, Bardeesy, N*. Pancreatic cancer metabolism: Breaking it down to build it back up. Cancer Discov, 2015 Dec;5(12):1247-61. *co-corresponding authors
  • Lee JJ*, Perera RM*, Wang, H, Wu, D, Lie XS, Han S, Fitamant J, Jones, PD, Ghanta KL, Kawano S, Nagle JM, Deshpande V, Boucher Y, Kato T, Chen JK, Willmann JK, Bardeesy N*, Beachy PA*. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. PNAS, 2014 Jul 29;111(30):E3091-100. *equal contributors.
  • Son J, Lyssiotis CA, Ying H, Wang X, Huan S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara, JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Glutamine supports pancreatic tumor growth through a Kras-regulated mechanism that maintains redox homeostasis. Nature, 2013 Apr 4;496(7443).
  • Perera RM and Bardeesy N. Ready, Set, Go: The EGF Receptor at the Pancreatic Cancer Starting Line. Cancer Cell, 2012 Sept 11; 22: 281-2
  • Perera RM and Bardeesy N. Cancer: When antioxidants are bad. Nature, 2011 July 6; 475: 43-44
  • Zoncu R*, Perera RM*, Balkin D, Toomre D, De Camilli P. A phosphoinositide switch controls the biogenesis and signaling properties of APPL endosomes. Cell 2009 Mar 20; 136(6):1110-21 (*equal contributors)
  • Perera RM, Zoncu R, Lucast L, De Camilli P, Toomre D. Two isoforms of synaptojanin 1 are recruited to clathrin coated pits at different stages. PNAS 2006 Dec; 103(51):19332-7

Selected Awards

  • 2014: Andrew L. Warshaw Institute for Pancreatic Cancer Research Fellowship
  • 2014-2016: Hirshberg Foundation for Pancreatic Cancer Seed Grant
  • 2015: American Association for Cancer Research (AACR) NextGEN STAR
  • 2016-2018: AACR-Pancreatic Cancer Action Network Career Development Award
Rushika M. Perera, PhD
  • Assistant Professor
  • Pathology

Specialty Areas

  • Cancer Research

Contact Information

Mailing/Shipping Address:

  • UCSF
  • Rushika M. Perera
  • Anatomy, Box 0452
  • 513 Parnassus Ave, HSW-1321/1301
  • San Francisco, CA 94143

Web Site

Other UCSF Organizational Association(s)

  • Department of Anatomy
  • Helen Diller Family comprehensive Cancer Center
  • Biomedical Sciences (BMS) Graduate Program
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