Lin Zhang

The immediate goal of our research is to understand how anticancer drugs kill cancer cells, and more importantly, why they fail so often. Our research has focused on proteins that control discrete steps of programmed cell death, including PUMA, Bax, BID, SMAC, and Mcl-1, which are directly or indirectly regulated by the most frequently mutated or altered tumor suppressors and oncogenes such as p53, APC, c-Myc and KRAS. Through analyses of these cell death regulators and their associated protein networks under the influence of oncogenic mutations and other alterations, we try to gain deep understanding on how cell death is initiated and executed in colon cancer cells, why some colon cancer cells are not sensitive to anticancer drugs, and what can be done to restore their sensitivity. Our long-term goal is to develop novel strategies and agents to improve colon cancer therapy and prevention.

The specific projects in our lab are focused on four areas: (1) understand how cell death regulators modulate therapeutic response; (2) determine how anticancer drugs kill colon cancer cells; (3) delineate the role of cancer stem cell in cancer prevention; and (4) identify novel small molecules to target cell death regulators to improve colon cancer therapy and prevention.

• V Foundation: Scholar Award, 2003
   – 2005
• General Motors (GM) Cancer Research Foundation: Scholar Award, 2003
   – 2005
• Edward Mallinckrodt, Jr. Foundation: Scholar Award, 2003
   – 2007
• University of Pittsburgh Cancer Institute: Junior Scholar Award, 2006
   – 2006
• American Lung Association (ALA)/Chest Foundation: Career Investigator Award, 2007
   – 2011
• American Cancer Society (ACS): Research Scholar Award, 2007
   – 2011
• Hillman Foundation: Hillman Fellow for Innovative Cancer Research, 2010
   – 2010
• University of Pittsburgh: Pitt Innovator Award, 2011
   – 2011

• Sichuan University, Chengdu, P.R.China — BS — 07/1990 — Biochemistry
• University of Southern California, Los Angeles, CA — PhD — 05/1995 — Molecular Biology
• Johns Hopkins University School of Medicine, Baltimore, MD — Postdoc — 04/1999 — Oncology

• Role of p73-mediated DR5 induction in therapeutic response to CDK inhibition.
  NIH · R01CA311678 · Jun 2, 2026 – May 31, 2031 · Role: Principal Investigator
• Therapeutic mechanisms of targeting WRN in MSI colorectal cancer.
  NIH · R01CA312130 · Jun 2, 2026 – May 31, 2031 · Role: Principal Investigator
• Highly tumor-selective pan RAS inactivators for targeting oncogenic RAS-driven cancers
  NIH · R01CA296154 · Aug 1, 2025 – May 31, 2030 · Role: Co-Investigator
• STING-dependent Intestinal Regeneration upon Radiation Injury
  NIH/NCI · R01CA260900 · Feb 9, 2022 – Jan 31, 2027 · Role: Co-Investigator
• Developmental therapy for selectively targeting the MEK-ERK pathway in cancer cells and the tumor stromal compartment
  NIH/NCI · R01CA254938 · Apr 7, 2021 – Mar 31, 2026 · Role: Co-Investigator
• BET degraders for improving colorectal cancer therapy
  NIH · R01CA248112 · Apr 1, 2021 – Mar 31, 2026 · Role: Principal Investigator
• Role of LSD1 in Triple Negative Breast Cancer Development and Therapeutic Response
  NIH/NCI · R01CA260357 · Mar 1, 2021 – Feb 28, 2026 · Role: Co-Investigator
• Targeting defective necroptosis in colorectal cancer
  NIH · R01CA247231 · Dec 1, 2019 – Mar 31, 2025 · Role: Principal Investigator
• Role of necroptosis in colorectal cancer therapy
  NIH · R01CA236271 · Jun 1, 2019 – May 31, 2024 · Role: Principal Investigator
• Novel Mcl-1 inhibitors for overcoming therapeutic resistance in colorectal cancer
  NIH · R01CA217141 · Jun 5, 2017 – May 31, 2022 · Role: Co-Principal Investigator
• Role of Mcl-1 degradation in colorecal cancer therapy
  NIH · R01CA203028 · Dec 9, 2015 – Nov 30, 2021 · Role: Principal Investigator
• Bid-mediated killing of oncogenic stem cells in chemoprevention
  NIH · R01CA172136 · Apr 1, 2013 – Mar 31, 2019 · Role: Principal Investigator
• SMAC in chemoprevention of colon cancer
  NIH · R01CA121105 · Sep 1, 2007 – Jul 31, 2013 · Role: Principal Investigator
• PUMA-mediated apoptosis in human cancer cells
  NIH · R01CA106348 · Apr 1, 2004 – Apr 30, 2016 · Role: Principal Investigator

• Cancer Biology
• Cancer Pharmacology
• Cell death
• Cancer therapy
• Drug resistance

• Lenz, Heinz-Josef
• Yu, Jian
• Chen, Dongshi
• Kaplowitz, Neil
• Wang, Rongfu
• Cohen, Pinchas