Ron Bose, M.D., Ph.D.

Associate Professor
Internal Medicine
Molecular Oncology
Cell Biology and Physiology

Cancer Biology Program
Molecular Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-747-9308

  • 314-747-9312

  • 314-747-3096 (secretary, Terrie Stald)

  • 314-747-9320

  • 8076

  • Debra and George W. Couch III Biomedical Research Building, Room 3310 (4515 McKinley Avenue)

  • rbose@dom.wustl.edu

  • http://ronboselab.org

  • cancer, genomics, organoids, 3D culture, receptor tyrosine kinase, signal transduction, next-generation sequencing, targeted therapy of cancer

  • Genomics and Cell Signaling in Breast Cancer

Research Abstract:

Dysregulation of signal transduction pathways plays a major role in the development of human cancers. We focus on the HER2 receptor tyrosine kinase, a member of the EGFR growth factor receptor family, which is gene amplified and activated in about 20% of human breast cancer cases. HER2 is a very important drug target, and there are five FDA-approved drugs commonly used in oncology clinics to bind and inhibit it.

PROJECT 1- HER2 Activating Mutations in Breast and Colon Cancer.

We were the first to identify HER2 activating mutations in breast cancers that were diagnosed as “HER2 negative.” This is a very important finding because these patients can benefit from HER2 targeted drugs, but are not offered them because their cancers are diagnosed as negative for HER2 gene amplification by routine pathology testing. Next-generation DNA sequencing test can readily identify these mutations. We have carefully studied these mutations in the lab, and identified how they activate HER2, what their drug sensitivity is, and are currently broadly exploring their role broadly in tumorigenesis. We identified a potent inhibitor for these mutations, neratinib, and launched the first clinical trial to prospectively treat metastatic breast cancer patients with HER2 mutations. This trial was successful and published in Clinical Cancer Research in 2017. We additionally found HER2 activating mutations in other solid tumors, including colon cancer, and we continue to study these mutations to understand how they interact with other oncogenes and tumor suppressor genes in order to maximize drug treatment for patients. We will presenting our latest work as an Oral Presentation at the American Association for Cancer Research (AACR) Annual Meeting on April 2, 2019.

PROJECT 2-Cancer Organoids

Organoids are a novel, 3-dimensional cell culture system that can grow primary human cancer cells with high efficiency and success rates. Organoid technology was first developed by Prof. Hans Clevers and colleagues in the Netherlands as a system to grow adult, intestinal stem cells and in the past 4 years, it has been demonstrated to be a powerful tool for cancer research. See review articles in Nature Reviews Cancer and the New England Journal of Medicine (M. Li et al., NEJM Feb 7, 2019 and Drost and Clevers, Nature Review Cancer, July 2018). Organoid culture methods represent a fundamental change in tissue culture, because it uses a defined set of growth factors, niche factors, and small molecule inhibitors to support the growth of cancer or stem cells. Organoids are a way to rapidly (weeks) grow primary patient samples and to test or study them in the laboratory. Further, organoids have enabled us to accelerate the study of HER2 mutations and we can perform drug testing on organoids in 96 and 384-well plates. We have been working with organoids for the past 2 years and will present results on this as an Oral Presentation at AACR Annual Meeting on April 2, 2019.

Please come talk to me to get more details about this research. I am very interested in having new graduate students, post-doctoral fellows, and undergraduates come to the lab.

Selected Publications:

Griffith OL, Spies NC, Anurag M, Griffith M, Luo J, Tu D, Yeo B, Kunisaki J, Miller CA, Krysiak K, Hundal J, Ainscough BJ, Skidmore ZL, CampbellK, Snider JE, Davies S, Kavuri SM, Chang EC, Magrini V, Larson DE, Fulton RS, Liu S, Leung S, Voduc D, Bose R, Dowsett M, Wilson RK, Nielsen TO, Mardis ER, Ellis MJ. The prognostic effects of somatic mutations in ER-positive breast cancer. Nature Communications. 2018 Sep 4; 9(1):3476. PMCID: PMC6123466

Ma CX*, Bose R*, Gao F, Freedman RA, Telli ML, Kimmick G, Winer E, Naughton MJ, Goetz MP, Russell CA, Tripathy D, Cobleigh MA, Forero A, Pluard TJ, Anders CK, Niravath PA, Thomas S, Anderson J, Bumb C, Banks KC, Lanman RB, Bryce R, Lalani AS, Pfeifer J, Hayes DF, Pegram MD, Blackwell K, Bedard PL, Al-Kateb H, Ellis MJ. Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Non-amplified Metastatic Breast Cancer. Clinical Cancer Research. Oct. 1, 2017. 23(19): 5687-5695. PMID: 28679771 *= co-first authors.

Kumar RD and Bose R. Analysis of somatic mutations across the kinome reveals loss-of-function mutations in multiple cancer types. Scientific Reports. 7(1):6418. July 25, 2017. PMCID: PMC5527104

Kumar RD, Swamidass SJ, Bose R. Unsupervised cancer driver detection with parsimony-guided learning. Nature Genetics, 48(10):1288-94 (2016). PMCID: PMC5328615

Kavuri SM, Jain N, Galimi F, Cottino F, Leto SM, Migliardi G, Searleman AC, Shen W, Monsey J, Trusolino L, Jacobs SA, Bertotti A, Bose R. HER2 Activating Mutations Are Targets for Colorectal Cancer Treatment. Cancer Discovery. 2015 Aug;5(8):832-41. doi: 10.1158/2159-8290.CD-14-1211. PubMed PMID: 26243863

Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discovery. 2013 Feb;3(2):224-37. doi: 10.1158/2159-8290.CD-12-0349. PubMed PMID: 23220880.

Ellis MJ, Ding L, Shen D, Luo J, SumanVJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, Ng S, Lin L, Crowder R, Snider, J, Ballman K, Weber J, Chen K, Koboldt DC, Kandoth C, Schierding WS, McMichael JF, Miller CA, Lu C, Harris CC, McLellan MD, Wendl MC, DeSchryver K, Allred DC, Esserman L, Unzeitig G, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Leitch M, Hunt K, Olson J, Tao Y, Maher CA, Fulton LF, Fulton RS, Harrison M, Oberkfell B, Du F, Demeter R, Vickery TL, Elhammali A, Piwnica-Worms H, McDonald S, Watson M, Dooling DJ, Ota D, Chang LW, Bose R, Ley TJ, Piwnica-Worms D, Stuart JM, Wilson RK, and Mardis ER. Whole Genome Sequencing to Characterise Breast Cancer Response to Aromatase Inhibition. Nature, 486: 353-360 (2012). PMCID: PMC3383766.

The Cancer Genome Atlas Research Network (the author list includes Bose R). Comprehensive molecular portraits of human breast tumors. Nature, 490: 61-70 (2012). PMCID: PMC3465532.

Last Updated: 3/22/2019 10:56:56 AM

Back To Top

Follow us: