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.
My research includes steroid hormone action, programmed cell death, apoptosis, and leukemia therapies.
- 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.
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 signals. Molecular 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 CW. The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor. Proc 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-263. Cell 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 survival. Proc Natl Acad Sci USA 111:1186-1191, 2014 PMCID: PMC3903247