Talha Anwar (right) with his mentor Celina Kleer, MD (left).Talha Anwar is in the Medical Scientist Training Program (MSTP) and the Molecular and Cellular Pathology Program at U-M. He defended his PhD thesis, Regulation of EZH2 in triple-negative breast cancer, on Friday April 6, 2018. Working in the laboratory of Celina G. Kleer, MD, Talha investigated how EZH2 functions and how it is controlled during breast cancer metastasis. Triple-negative breast cancers constitute an aggressive subtype of the disease, and, although they represent 15-20% of all breast carcinomas, they are responsible for a disproportionately high number of deaths. This is due to the development of distant metastasis. Despite advances in breast cancer diagnosis and treatment, the key molecular alterations and drivers of metastasis in triple-negative breast cancers are still undefined, and therapies are limited.
The Kleer lab has reported that EZH2, an epigenetic transcriptional regulator, is overexpressed in aggressive breast cancers, and is associated with worse patient outcome. However, the mechanisms were largely undefined. Talha’s work during the past 4 and a half years reveals that EZH2 phosphorylation at threonine 367 in breast cancer cells results in cytoplasmic localization of EZH2, where it functions by a completely novel mechanism, which is independent of its epigenetic repressor function and involves binding to cytoskeletal regulators to promote breast cancer cell migration, invasion, and metastasis. Through the development of a new antibody against phosphorylated EZH2 (T367), this work reveals that the protein is increased in the cytoplasm of breast cancer metastasis. He has identified that the signal transduction protein p38 MAPK is responsible for EZH2 phosphorylation in breast cancer. The results of his thesis may lead to future therapeutic targets for metastatic triple-negative breast cancer, and novel biomarkers of disease progression.
Talha has had a very successful graduate tenure, with 4 publications and 1 paper resubmitted under review. In addition, he has garnered the following prestigious awards:
Dr. Anwar will return to Medical School to complete the clinical portion of his MD/PhD training.