Ming Chen, PhD, has been awarded two new National Institutes of Health (NIH) RO1 grants, which will begin in March and April 2022, respectively. These grants will support the Chen Lab’s research centered on the molecular and genetic events underlying cancer progression and metastasis, and their long–term goal of developing new therapeutic strategies for preventing and treating metastatic disease.
Approximately 10% of the cancer genome is affected by large chromosomal deletions. Genetically engineered mouse models generally provide an ideal tool for investigating the consequences of genetic aberrations in tumor biology. However, due to the limited cloning capacity of targeting vectors (~300 Kb) and the rarity of on-target homologous recombination events in traditional gene-targeting technology, modelling large chromosomal deletions in mice has proved highly challenging, and the in vivo role of these deletions in tumorigenesis has therefore been significantly understudied. The first of the Chen Lab’s RO1 grants, titled “Engineering Large Chromosomal Deletions in Mice to Advance Precision Oncology,” will fund the lab’s efforts to develop novel mouse models of prostate cancer harboring large chromosomal deletions using CRISPR/Cas9 technology, with a goal of validating and credentialing these models as genetically and biologically robust representations of human prostate cancer.
Mutations in the retinoblastoma tumor suppressor gene RB1 are common in a wide spectrum of pediatric and adult cancers, including metastatic castration-resistant prostate cancer (mCRPC). Recent studies have identified RB1 genomic alteration as the molecular factor most strongly associated with poor clinical outcomes in patients with mCRPC, highlighting loss of RB function as a dominant driver of prostate cancer lethality, and underscoring the critical need for new therapeutic strategies targeting this mechanism for the treatment of lethal RB1-deficient prostate cancer. Preliminary data from the Chen Lab have demonstrated that RB1 disruptions significantly sensitize prostate cancer cells to ferroptosis, a form of regulated cell death that could be harnessed for cancer therapy. The second of the Chen Lab’s RO1 grants, titled “Targeting Ferroptosis in Lethal RB1 Deficient Prostate Cancer,” will fund the lab’s efforts to determine whether targeting ferroptosis is an effective therapeutic approach to treating lethal RB1-deficient prostate cancer in preclinical prostate cancer models.
Chen is an Assistant Professor of Pathology. To learn more about the Chen Lab's research, please click here.