Faculty
Ron Bose.jpg

Ron Bose, MD, PhD

Associate Professor
Department of Medicine
Oncology Division
Molecular Oncology & Developmental Therapeutics
Department of Cell Biology & Physiology

Clinical Interests

  • Her2-positive breast cancer
  • Breast cancer

Research Interests

  • Her2/neu tyrosine kinase
  • Genomics of breast cancer
  • Use of proteomics to study breast cancer cell signaling

Contact

  • 314-747-9308 (tel)
  • 314-747-9320 (fax)
  • 4515 McKinley Research Building, Room 3310 (office)
  • Division of Oncology
    Campus Box 8076
    Washington University Medical School
    660 South Euclid Avenue
    St. Louis, MO 63110
  • Bose lab website

Research

Breast cancer is typically divided into 3 major subtypes (hormone receptor positive, HER2 positive, and triple negative breast cancer). However, new genomics research has provided a new classification system for breast cancer (Luminal A, Luminal B, Basal-like, and HER2-enriched breast cancer). This research is showing that there are different spectrum of mutations and genetic alterations for each of these new categories. Basal-like breast cancer, a category that overlaps substantially with triple negative breast cancer, is characterized by an extremely high rate of mutations in a critical tumor suppressor gene, p53. This characteristic is shared by ovarian cancer and comparison of basal-like breast cancer and ovarian cancer suggests they share a lot of similarities. Hormonal receptor positive breast cancers can be divided into the new categories, Luminal A and Luminal B, with the Luminal A patients having a better prognosis. The mutation patterns in Luminal A versus B patients provide some understanding as to why this is so. HER2-enriched breast cancers are closely related to the prior category of HER2 positive breast cancers, but there are still some questions in the breast cancer field as to how a few patients can be “HER2-enriched” without having HER2 gene amplification (the defining characteristic of HER2 positive breast cancers). This is an active area of research. These findings have been published in the scientific journal, Nature, and have been described in the New York Times and the St. Louis Post-Dispatch (front pages articles in both papers on Sept 24, 2012). Dr. Bose and his lab have played an important part in developing this genomic understand of breast cancer.

A major goal of breast cancer genomics is to identify new gene targets in breast cancer for drug treatment and over 40 new possible gene targets have been identified by breast cancer genomics. Dr. Bose and his lab are taking these results forward to produce new breast cancer treatments for patients. Broadly, his research takes a 3 step approach: 1) Identify promising gene targets based on computer analysis of breast cancer genomes. 2) Perform direct testing of the genes and the proteins that they produce in the laboratory. 3) Launch clinical trials for the most promising gene targets. This process is ongoing and Dr. Bose and 2 other Oncology faculty, Drs. Cynthia Ma and Matthew Ellis, have gotten FDA-approval to start the very first genome based clinical trial.

Dr. Bose’s lab has a major interest in breast cancer cell signaling and in particular, the Her2 tyrosine kinase, which is a major protein in these cell signaling pathways. Cancer cell signaling promotes cancer cell growth and spread and is therefore a major target in the treatment of cancers. Dr. Bose has been working on the Her2 tyrosine kinase since 2003, when he was medical oncology fellow at Johns Hopkins School of Medicine. Dr. Bose has published over 8 scientific and medical papers on Her2 and its closely related proteins. Dr. Bose’s interest in cancer cell signaling started back in 1993, when he was an MD-PhD student doing research at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City. MSKCC has an affiliation with Cornell University and the joint Cornell University-MSKCC-Rockefeller University MD-PhD program, which Dr. Bose is a graduate of, is one of the top 10 MD-PhD programs in the nation.

Dr. Bose’s current research project include: 1) Studying breast cancer genomic alterations that affect cancer cell signaling. 2) Studying the biochemistry of the Her2 tyrosine kinase to determine if there are new ways to target it with drugs. 3) Study the development of resistance to current Her2 targeted drugs, such as the monoclonal antibody Herceptin, because the development of drug resistance in patient’s cancers creates a very large medical problem for patient treatment.

Dr. Bose sees patients one day each week at the Siteman Cancer Center at Barnes-Jewish West County Hospital. He sees patients with all types of breast cancer. He is particularly interested in patients with HER2-positive breast cancer and provides them information on the latest clinical trials for HER2.

 

EGFR kinase

Structures of EGFR kinase domain bound to small molecule kinase inhibitors

(A) Erlotinib–EGFR structure; (B) Lapatinib–EGFR structure; (C) HKI-272–EGFR structure. The panels show the entire EGFR kinase domain with inhibitor bound, revealing the active (A) and inactive (B and C) conformations of EGFR.
From: Bose R, Zhang X. The ErbB kinase domain: structural perspectives into kinase activation and inhibition. Exp Cell Res 2009 Feb 15;315(4):649-58

 

Kinase activation

Kinase activation of Her4 homodimers or Her4-Her3 heterodimers in vitro

(A) Predicted effects of the Her4 mutations and of Her3 on Her4 kinase activity. The mutations shown here are in the Her4 kinase domain. (B) Her4 and Her3 kinase domain proteins were mixed at 1:1 molar ratio, liposomes containing nickel-chelating lipids were added and kinase assay performed based on phosphotransfer to an exogenous peptide substrate.
From: Monsey J, Shen W, Schlesinger P, Bose R. Her4 and Her2/neu tyrosine kinase domains dimerize and activate in a reconstituted in vitro system. J Biol Chem 2010 Mar 5;285(10):7035-44