Molecular mechanisms driving therapy-induced lineage plasticity

SUMMARY This proposal seeks Dr. Juan Francisco Linares’s salary as a Research Specialist to support Dr. Maria T. Diaz-Meco’s research program at the Weill Cornell Medicine Department of Pathology and Laboratory Medicine to study the molecular and cellular mechanisms that regulate lineage plasticity in prostate cancer. The elucidation of the molecular mechanisms that castration-resistant prostate cancer cells (CRPC) use to evade therapeutic pressures requires scientists with an in-depth understanding of the molecular biology of this process, but also with the required technical expertise in in vivo mouse models that faithfully recapitulate human disease, as well as the necessary bioinformatics tools to perform rigorously epigenetic analysis. Therefore, with this Research Specialist Award, we intend to provide stable research opportunities for the exceptional scientist Juan Francisco Linares to develop impactful research in this area of expertise. He has made seminal contributions in signaling, inflammation, metabolism, and cancer and has solid interdisciplinary training that will be critical for the project’s success. He will contribute to the research program focused on defining the molecular and cellular mechanisms that drive the differentiation of CRPC to more aggressive prostate cancer variants, such as Neuroendocrine and Mesenchymal prostate cancer. With his expertise in cancer biology and cancer metabolism and his capacity to apply novel mouse models and bioinformatics approaches, he is filling a unique niche within the Diaz-Meco lab that will provide continuity, stability, and detailed scientific knowledge to achieve the aims of the NCI-funded grants. Dr. Linares’s long-time expertise and dedication will advance our understanding of the lineage plasticity in CRPC to help design more effective therapies to overcome the acquired resistance in prostate cancer.