Haobin Chen, MD, PhD

Haobin Chen, MD, PhD

Assistant Professor

Address:
Division of Oncology
Mail Stop 8056-0029-11
Washington University
660 South Euclid Avenue
St. Louis, MO 63110

Room 554, McDonnell Medical Sciences Building (office)

Room 554, McDonnell Medical Sciences Building (lab)

Admin:
Roslyn Davis
simmsr@wustl.edu

Clinical Interests
  • Lung cancer
  • Mesothelioma
  • Thymic malignancies
Research Interests
  • Small cell lung cancer
  • Targeted therapy
  • Tumor heterogeneity
  • Immune evasion
Research

Small-cell lung cancer (SCLC) is recalcitrant cancer and the most aggressive form of lung malignancy. It typically metastasizes early and develops resistance to chemotherapy rapidly. There is growing evidence that SCLC is a heterogeneous group of malignancies. The previous work in my lab focused on the preclinical development of targeted therapy for SCLC-N subtype tumors. We were also one of the first groups to characterize various therapeutic markers in different molecular subtypes of SCLC tumors.

1) BET inhibitors are a potential targeted therapy for SCLC-N subtype tumors (Mol Cancer Res, 2023;21(2):91-101)

1) BET inhibitors are a potential targeted therapy for SCLC-N subtype tumors (Mol Cancer Res, 2023;21(2):91-101)
We tested our hypothesis that targeting transcriptional coactivator(s) may effectively block the functions of the master transcriptional factors (TFs) in SCLC. NEUROD1 (ND1) is a master TF in SCLC-N tumors. We found that BET bromodomain proteins (e.g., BRD4) are transcriptional coactivators of NEUROD1, and blocking their functions could suppress NEUROD1’s activity. We demonstrated that SCLC-N cell lines and tumors are sensitive to BET inhibitors (BETi) in vitro and in vivo, respectively.

2) High-throughput drug screens led to our finding that mTOR inhibitors potentiate the antitumor activities of BET inhibitors in SCLC (JCI Insight, 2023, In press)

BET inhibitors induce mitochondrial apoptosis in SCLC, but this antitumor effect is lessened by the induction of RSK3 – a kinase upstream of mTOR kinase. Activation of mTOR signaling by RSK3 increases tumor survival upon BET inhibitor (BETi) treatment. mTOR inhibitors (mTORi) abrogate this pro-survival signaling and amplify BETi-induced apoptosis.

3) Characterization of various therapeutic markers in different molecular subtypes of SCLC (Journal of Thoracic Oncology, 2022 Jan;17(1):141-153)

Characterization of various therapeutic markers in different molecular subtypes of SCLC (Journal of Thoracic Oncology, 2022 Jan;17(1):141-153)
Left, Representative IHC staining images of CD8 show three different CD8+ T-cell immunophenotypes in primary SCLC tumors. Right, the ASCL1/NEUROD1-subtype tumors more commonly present a ‘desert’ CD8 immunophenotype, while other subtypes more frequently manifest an ‘inflamed’ picture. Our findings suggest that the non-ASCL1/NEUROD1 subtypes of SCLC tumors are more likely to respond to immunotherapy.

The current work in the lab centers on understanding what drives heterogeneity in SCLC tumors and how to make SCLC more responsive to immunotherapy.

Biosketch

Education

  • 2016-2013: Fellow, Medical Oncology, National Cancer Institute, NIH, Bethesda, MD
  • 2013-2010: Resident, Internal Medicine, Kingsbrook Jewish Medical Center, Brooklyn, NY
  • 2006-2000: PhD, New York University, New York, NY
  • 2000-1999: Resident, East China Hospital, Shanghai, China
  • 1999-1992: MD, Shanghai Medical College Fudan University, Shanghai, China

Academic Positions & Employment

  • present-2022: Assistant Professor of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO
  • 2022-2016: Physician-Scientist Early Investigator, Thoracic Surgery Branch, National Cancer Institute, NIH, Bethesda, MD
  • 2010-2006: Research Assistant Professor, Department of Environmental Sciences, New York University, New York, NY

Board Certification

  • 2015: American Board of Internal Medicine, Medical Oncology
  • 2013: American Board of Internal Medicine, Internal Medicine

Honors & Awards

  • 2017: Young Investigator Award, Asian and Pacific Islander American Organization, NIH
  • 2006: 1st Place Predoctoral Research Award, Society of Toxicology, USA
  • 1998: HuaZang Scholarship, Shanghai Medical College Fudan University, Shanghai, China
  • 1997: GuangHua Scholarship, Shanghai Medical College Fudan University, Shanghai, China
  • 1996: 3rd Place People’s Scholarship, Shanghai Medical College Fudan University, Shanghai, China