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Ronald John Buckanovich, MD, PhD

Professor of Medicine, Director of the Ovarian Cancer Center of Excellence, Co-Director of the Women's Cancer Research Center

I envision a world in which mothers do not die of ovarian cancer, but live to watch their children and grandchildren grow up. We are working towards this goal by developing ways to prevent the disease, better tests to diagnose the disease at a curable stage, and new treatments to increase cure rates for those who do get the disease.
Ronald John Buckanovich, MD, PhD

Research in Brief

Ronald Buckanovich graduated from Cornell University in 1990 with a B.S. in Genetics and Biochemistry. He then completed the Medical Scientist Training Program and started his life-long study of ovarian cancer. He received his Ph.D. in 1996 from the Rockefeller University and his M.D. in 1998 from Cornell University. Dr. Buckanovich then went on to complete an Internal Medicine residency and a Hematology-Oncology fellowship at the Hospital of the University of Pennsylvania. During his fellowship he continued his research on ovarian cancer, identifying dozens of novel clinical targets and helped to develop a novel therapeutic to enhance tumor vaccine therapy. Dr. Buckanovich joined the University of Michigan as an Assistant Professor of Internal Medicine in 2006. There he identified a novel population of cancer stem-like cells (CSCs) which may be responsible for ovarian cancer metastasis, chemotherapy resistance and ultimately disease recurrence. His laboratory is now studying the factors which regulate these CSCs including regulators of asymmetric division and quiescence. His laboratory has identified two novel compounds which directly target cancer stem cells; one which blocks the ability of these cells to metastasize, and a second which selectively kills the cancer stem-like cells. Both of these drugs are now being developed for first in human clinical trials.

In addition to his laboratory studies, Dr. Buckanovich has a busy clinical practice, specializing in the treatment of ovarian and uterine cancers. He is currently the principal investigator of two clinical trials at the University of Pittsburgh. He has been an author or co-author of 60 original research articles. In recognition of his work, Dr. Buckanovich received a Clinical Investigator Award from the Damon Runyon Cancer Research Foundation, the National Institutes of Health New Innovator – Directors Award, Society of Gynecologic Oncology Best Basic Science Award, and he has been elected to the American Society of Clinical Investigators.

Research

Cancer stem cells (CSC) are rare, inherently chemoresistant cells, which have the capacity to divide both symmetrically (creating more CSC) or asymmetrically (generating non CSC cancer cells and tumor heterogeneity). CSC are hypothesized to be the primary source of cancer metastasis, recurrence and ultimately a patients demise. The primary objective of my laboratory is to understand regulators of cancer stem cell proliferation and division patterns with the goal of developing novel therapeutics targeting CSC. In order to complete these studies, in collaboration with Euisik Yoon, we have developed novel in vitro microfluidics devices as a means to study symmetric vs asymmetric divisions of CSC, regulators of CSC, and mediators of CSC quiescence. In addition we are developing and novel humanizes stroma tumor model. We believe that this tumor model, by virtue of having a human tumor stroma, more accurately

  • Chefetz I, Grimley E, Yang K, Hong L, Vinogradova EV, Suciu R, Kovalenko I, Karnak D, Morgan CA, Chtcherbinine M, Buchman C, Huddle B, Barraza S, Morgan M, Bernstein KA, Yoon E, Lombard DB, Bild A, Mehta G, Romero I, Chiang CY, Landen C, Cravatt B, Hurley TD, Larsen SD, Buckanovich RJ. A Pan-ALDH1A Inhibitor Induces Necroptosis in Ovarian Cancer Stem-Like Cells. Cell Rep. 2019 Mar 12:26(11):3061-3075.e6, doi:10.1016/j.celrep.2019.02.032. PMID: 30865894
  • McLean K, Tan L, Bolland D, Coffman L, Peterson L, Talpaz M, Neamati N and Buckanovich RJ. Leukemia Inhibitory Factor Functions in Parallel with Interleukin-6 to Promote Ovarian Cancer Growth”. Oncogene 2019 Feb;38(9): 1576-1584. Doi: 10.1038/s41388-018-0523-6. Epub 2018 Oct 10. PMID: 30305729
  • Coffman LG, Pearson AT, Frisbie LG, Freeman Z, Christie L, Bowtell DD, and BuckanovichRJ. Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma. Stem Cells 2019 Feb;37(2):257-269. Doi: 10.1002/stem2932. Epub 2018 Nov. 2 PMID: 30353617
  • Huddle BC, Grimley E, Buchman CD, Chtcherbinine M, Debnath B, Mehat P, Yang K, Morgan CA, Li S, Felton JA, Sun D, Metha G, Neamati N, Buckanovich RJ, Hurley TD and Larsen SD. Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy. J Med Chem. 2018 Sep 28;doi:10.1021/acs. (Epub ahead of print) PMID: 30221940
  • Raghavan S, Mehta P, Ward M, Bregenzer M, Fleck E, Tan L, McLean K, Buckanovich R, Mehta G: Personalized medicine based approach to model patterns of chemoresistance and tumor recurrence using ovarian cancer stem cell spheroids Clinical Cancer Research.2017 Nov 15;23(22):6934-6945. PMID: 28814433
  • Vergote IB, Smith DC, Berger R, Kurzrock R, Vogelzang NJ, Sella A, Wheler J, lee Y, Foster PG, Weitzman R, Buckanovich RJ: A phase 2 randomised discontinuation trial of cabozantinib in patients with ovarian carcinoma European Journal of Cancer 83: 229-236, 2017. PMID: 28755607
  • Bai S, Ingram P, Chen YC, Deng N, Pearson A, Niknafs Y, O'Hayer P, Wang Y, Zhang ZY, Boscolo E, Bischoff J, Yoon E, Buckanovich RJ: EGFL6 regulates the asymmetric division, maintenance, and metastasis of ALDH+ ovarian cancer cells. Cancer Res 76(21): 6396-6409, 2016. PM27803106/PMC5120866
  • Choi YJ, Ingram PN, Yang K, Coffman L, Iyengar M, Bai S, Thomas DG, Yoon E, Buckanovich RJ: Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2. Proc Natl Acad Sci U S A 112(50): E6882-8, 2015. PM26621735/PMC4687560
  • McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S, Cabrera L, Keller E, McCauley L, Cho KR, Buckanovich RJ: Human ovarian carcinoma–associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Invest 121(8): 3206-19, 2011. PM21737876/PMC3148732
  • Silva IA, Bai S, McLean K, Yang K, Griffith K, Thomas D, Ginestier C, Johnston C, Kueck A, Reynolds RK, Wicha MS, Buckanovich RJ: Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res 71(11): 3991-4001, 2011. PM21498635/PMC3107359

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