Early Investigator Research Awards Expand Prostate Cancer Fellows Research

DoD grants support biomarker investigations, CRISPR research

Mohammad Alyamani, PhD, and Kelsey Bohn, PhD, postdoctoral fellows in the laboratory of Nima Sharifi, MDDepartment of Cancer Biology, received Department of Defense (DoD) Prostate Cancer Research Program Early Investigator Research Awards. These prestigious awards will enable Drs. Alyamani and Bohn to contribute to the lab’s innovative prostate cancer research while launching their own independent research careers.

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Identifying biomarkers of treatment resistance in prostate cancer

Dr. Alyamani will use his DoD funds to study how prostate cancer drugs are metabolized and how their byproducts (metabolites) may affect the progression of prostate cancer.

The Sharifi lab recently found that patients with advanced prostate cancer and a specific genetic variant metabolize the drug abiraterone differently than men without the variant. Men with the genetic anomaly have high levels of a particular metabolite that can actually “turn on” pro-cancer pathways.

With the DoD funds, Dr. Alyamani will use data from a previous study of abiraterone to correlate metabolite levels with clinical indicators of disease. The ultimate goal of the project is to uncover how drug metabolites may be used as biomarkers for patients at high risk for developing treatment resistance and may be better suited for different treatment strategies.

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Elucidating role of alternative hormones in treatment-resistant prostate cancer

In 2013, Dr. Sharifi discovered that men with advanced prostate cancer and a specific genetic variant are more likely to die from their prostate cancer. His team showed that this genetic variant enabled prostate cancer cells to use an alternative source of androgens when their first-line supply was depleted following androgen-deprivation therapy.

Dr. Bohn will use her DoD funds to investigate how these alternative androgren sources drive abiraterone-resistant prostate cancer.

The award gives Dr. Bohn the opportunity to take a closer look at the mechanisms within the cancer cells that enable them to evade abiraterone treatment. To characterize what exactly occurs within the cells to confer resistance, she will intracellularly monitor enzyme activity and receptor signaling and will use CRISPR/Cas9 gene editing technology to identify genes important to resistance.

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The DoD’s Prostate Cancer Research Program — part of the Congressionally Directed Medical Research Program, which has many disease-focused programs — funds research into biomarker development, genetics, imaging, mechanisms of resistance, survivorship and palliative care, therapy, and tumor and microenvironment biology related to prostate cancer.