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Joshua LaBaer, MD, PhD
Virginia G. Piper Center for Personalized Diagnostics
Professor of Chemistry and Biochemistry
The Biodesign Institute
Arizona State University
Goal: To identify new therapeutic targets to treat highly aggressive breast cancer.
Impact: Dr. LaBaer is studying a tumor suppressor gene and the protein it encodes, called p53. Mutations in p53 are often found in triple-negative breast cancer (TNBC), making p53 a potential target for treating this aggressive subtype of breast cancer. Dr. LaBaer is investigating ways to reactivate the tumor-suppressing powers of mutated p53 protein in order to inform the development of combination approaches and personalized therapies for TNBC.
What’s next: He and his team will look for drug-targetable combinations of mutations that co-exist and partner with mutant p53 to lead to tumor progression.
Triple negative breast cancer (TNBC) is so called because it does not rely on the estrogen, progesterone, or HER2 receptors, as most other breast cancers. This currently makes TNBC difficult to treat. In many cases, TNBC tumors have mutations in a tumor-suppressing protein called p53, which helps drive the aggressive nature of this disease. Dr. LaBaer is looking for ways to restore mutated p53 to its normal function of inhibiting the development and growth of cancer.
Full Research Summary
Research area: Identifying new ways to treat triple negative breast cancer (TNBC).
Impact: TNBCs are those that lack expression of estrogen receptor (ER), progesterone receptor (PR), and HER2. Because most TNBC lack an established target, it can be difficult to treat. It also tends to be more aggressive, more prone to spreading, and has a poorer prognosis than other subtypes of breast cancer.
In 80 percent of TNBC cases, there are mutations in a gene and the protein it encodes, called p53, that contributes to the aggressive nature of the disease. Mutations in p53 alone, however, do not cause cancer, and researchers have struggled to find ways to treat p53-mutated cancers. Dr. LaBaer’s work is aimed at identifying mutations in p53 “co-driver” genes and pathways of mutant p53 proteins that can be targetable. His findings could lead to the development of new combination approaches and personalized therapy for patients with TNBC.
Current investigation: Dr. LaBaer and his colleagues have been developing innovative molecular technologies that can simultaneously test thousands of potential “co-driver” genes for each type of p53 mutations.
What he’s learned so far: The team has identified key individual mutations that can initiate metastasis in collaboration with mutant p53.
What’s next: Dr. LaBaer will expand his search to identify novel combinations of mutations that lead to cancer progression.
Joshua LaBaer is one of the nation's foremost investigators in the rapidly expanding field of personalized medicine. Formerly director of the Harvard Institute of Proteomics (HIP), he was recruited to ASU's Biodesign Institute as the first Piper Chair in Personalized Medicine. Dr. LaBaer's efforts involve leveraging the Center's formidable resources for the discovery and validation of biomarkers—unique molecular fingerprints of disease—which can provide early warning for those at risk of major illnesses, including cancer and diabetes. This work is carried out in conjunction with the Partnership for Personalized Medicine, a multi-institution effort that includes the Translational Genomics Research Institute in Phoenix and the Fred Hutchinson Cancer Research Institute in Seattle.
Dr. LaBaer is a board certified physician in Internal Medicine and Medical Oncology and was an Instructor and Clinical Fellow in Medicine at Harvard Medical School and now serves as Adjunct Professor of Medicine, Mayo Clinic. He has contributed to over 140 original research publications, is an associate editor of the Journal of Proteome Research, a member of the editorial boards of Analytical Biochemistry, Current Opinion in Biotechnology, Cancer Biomarkers, Molecular Biosystems, and Clinical Proteomics. Formerly a member of the NCI’s Board of Scientific Advisors, he serves as chair of the NCI’s Early Detection Research Network Executive Committee and Co-Chair of its Steering Committee. He is the president of the US Human Proteome Organization and serves on a number of government and industry scientific advisory boards. He earned his medical degree and doctorate (biochemistry and biophysics) at University of California, San Francisco.