Freeland, Jack
Jack is in the Cell & Developmental Biology (CDB) home area of the MBIDP, and joined the CMB Training Program in 2022.
Mentor: Dr. Thomas Graeber
Despite the advent of novel drugs, improved surgical techniques, and earlier detection rates, the survival rate of prostate cancer has not improved in recent years. The majority of prostate cancer deaths stem from patients progressing from an adenocarcinoma phenotype (PCa) to a highly aggressive neuroendocrine phenotype (NEPC). Cases of organ-confined PCa are generally close to diploid while metastatic and lethal castration resistant prostate cancers (CRPC) such as NEPC exhibit high degrees of aneuploidy. We hypothesize that along with activating oncogene mutations and loss of tumor suppressor genes, accumulative coordinate changes in DNA copy number alteration (CNA) patterns contribute to aggressive cancer phenotypes. Thus, tumors with few or no strongly activating oncogene mutations may rely more heavily on CNA for phenotype changes (prostate cancer). The goal of my project is to better understand the role of genomic instability and aneuploidy in the aggressiveness of NEPC. I will first investigate how inducing genomic instability in our patient derived NEPC model changes the phenotype in vitro and in vivo. I will then investigate if novel bioinformatically implicated genes can affect genomic instability or act as therapeutic targets against NEPC.
