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James M. Rae, PhD

University of Michigan
Ann Arbor, Michigan

Titles and Affiliations

Associate Professor of Internal Medicine
Associate Professor of Pharmacology

Research area

Developing new treatments for anti-estrogen resistant ER-positive breast cancer.


Approximately 70 percent of patients with breast cancer have estrogen receptor (ER)-positive breast cancer. Drugs that block ER signaling are effective in the prevention and treatment of both early and advanced disease. However, nearly a third of patients with newly diagnosed ER-positive breast cancer receiving a currently approved anti-estrogen therapy will suffer a metastatic recurrence, and nearly all patients with ER-positive metastatic breast cancer (MBC) ultimately become resistant to all known anti-estrogens drugs and succumb to their disease. There is a critical unmet need to develop more effective drugs targeting ER-positive breast cancer.

What’s next

Recently, Dr. Rae and other researchers have discovered common recurring mutations in the Estrogen Receptor 1 (ESR1) gene in metastatic anti-estrogen resistant breast cancers. Studies show that these ESR1 mutations confer ER signaling activity in the absence of estrogen and that cells harboring these mutations are resistant to all current anti-estrogen treatments including tamoxifen, fulvestrant and aromatase inhibitors. Protein degradation has emerged as a promising therapeutic strategy for development of drugs, especially for cancers. The technology employs specialized molecules called PROTACs that can target specific proteins for degradation. Dr. Rae and his team hypothesize that PROTACs designed to degrade normal ER and ESR1 mutant ERs will prove superior to current estrogen-targeted therapies and will revolutionize the treatment of breast cancers. Using start-of-the-art chemistry with fellow BCRF Investigator, Dr. Shaomeng Wang, they have developed a large series of PROTAC ER degraders. They will test their efficacy using several preclinical breast cancer models and determine the efficacy of ER PROTACs degraders in combination with CDK4/6 inhibitors which have become the standard of care in metastatic ER-positive breast cancers. Successful completion of this project will lead to clinical trials aimed at expanding treatment options for patients with anti-estrogen resistant ER-positive breast cancer.


James M. Rae, PhD is a research scientist with principal expertise in breast cancer and studies multiple aspects of cancer pharmacology including novel drug development, metabolism, pharmacokinetics and dynamics, and genomics, and biomarker identification and characterization. He holds faculty appointments in the Department of Internal Medicine and the Department of Pharmacology at University of Michigan. He is involved in several large team science studies and has been a member of the National Cancer Institute’s (NCI) National Clinical Trials Network (NCTN) and the South West Oncology Group (SWOG) where he serves as the Executive Officer of Translational Medicine. He also serves on the NCTN Biospecimen Banks Group Banking Committee. He is a recognized expert in the field of breast cancer research with a primary focus on the pharmacology of drugs that antagonize estrogen receptor signaling.

BCRF Investigator Since


Donor Recognition

The Macy's Award

Areas of Focus

Tumor Biology