Clark W. Distelhorst, MD

Charles S. Britton II Professor of Hematology/Oncology
School of Medicine
Department of Medicine
Division of Hematology and Oncology
School of Medicine
Department of Pharmacology
School of Medicine
Molecular Oncology Program
Case Comprehensive Cancer Center

Dr. Distelhorst earned BA and MD degrees Summa Cum Laude at Ohio State University. He then trained in Internal Medicine at Yale, followed by training in Internal Medicine and Hematology/Oncology at Washington University School of Medicine in St Louis. Here he received intensive basic research training under Professors Stuart Kornfeld and Philip Majerus. Most of his research career has been at Case Western Reserve University School of Medicine in Pharmacology, Hematology/Oncology and the Case Comprehensive Cancer Center. In 2003 he worked at the Babraham Institute, Cambridge, UK, with Sir Michael Berridge, Martin Bootman and Llewelyn Roderisk. This work enabled the Distelhorst lab to employ single-cell digital imaging in their discovery of Bcl-2-IP3R interaction. In collaboration with Jan Parys and colleagues in Leuven, Belgium, we established the importance of targeting Bcl-2-IP3R interaction to treat Bcl-2 positive malignancies.

Research Information

Research Interests

  • Mechanism by which the Bcl-2 protein regulates calcium signaling and cell death, with novel approaches to target the Bcl-2 protein to induce cell death in cancer cells.
  • Mechanism of glucocorticosteroid hormone induce apoptosis in malignant lymphocytes.
  • Most recent discovery, providing novel insight into the role of pyruvate kinase in cancer cells.

External Appointments

Physician, Department of Hematology and Oncology
University Hospitals Cleveland Medical Center


Rong Y, Aromolaran AS, Bultynck G, Zhong F, Li X, McColl KS, Herlitze S, Matsuyama S, Roderick HL, Bootman MD, Mignery GA, Parys JB, De Smedt H, Distelhorst CW. Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2's inhibition of apoptotic calcium signalsMolecular Cell 31:255-265, 2008. PMCID: PMC3660092

Rong Y, Bultynck G, Aromolaran AS, Zhong F, Parys JB, De Smedt H, Mignery GA, Roderick HL, Bootman MD, Distelhorst CWThe BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptorProc Natl Acad Sci USA 106:14397-14402, 2009. PMCID: PMC2728114

Greenberg, E.F., McColl, K.S., Zhong, F., Wildey, G., Dowlati, A., Distelhorst, CW. Synergistic killing of human small cell lung cancer cells by the Bcl-2-inositol 1,4,5-trisphosphate receptor disruptor BIRD-2 and the BH3-mimetic ABT-263Cell Death and Disease 6:e2034, 2015. PMCID: PMC4720890

Chang MJ, Zhong F, Lavik AR, Parys JB, Berridge MJ, Distelhorst CW. Feedback regulation mediated by Bcl-2 and DARPP-32 regulates inositol 1,4,5-trisphosphate receptor phosphorylation and promotes cell survivalProc Natl Acad Sci USA 111:1186-1191, 2014 PMCID: PMC3903247