Molecular mechanisms driving therapy-induced lineage plasticity

摘要 这项提案寻求胡安·弗朗西斯科·利纳雷斯博士作为研究专家的薪水，以支持玛丽亚·T。 Diaz-Meco在威尔·康奈尔大学病理和实验室医学系的研究项目 目的：研究前列腺癌家族可塑性调控的分子和细胞机制。这个 抗去势前列腺癌细胞(CRPC)逃避的分子机制研究 治疗压力需要科学家对这一过程的分子生物学有深入的了解， 而且还拥有在活体小鼠模型中所需的技术专长，这些模型忠实地概括了人类疾病， 以及必要的生物信息学工具来进行严格的表观遗传分析。因此，有了这个 研究专家奖，我们打算为杰出的科学家胡安提供稳定的研究机会 弗朗西斯科·利纳雷斯在这一专业领域开展有影响力的研究。他在中国做出了开创性的贡献 信号、炎症、新陈代谢和癌症，并接受了扎实的跨学科培训，这对 项目的成功。他将为专注于定义分子和细胞的研究计划做出贡献 促使CRPC分化为更具侵袭性的前列腺癌变异的机制，如 神经内分泌和间叶性前列腺癌。凭借他在癌症生物学和癌症新陈代谢方面的专长 以及应用新的老鼠模型和生物信息学方法的能力，他正在填补一个独特的利基市场 Diaz-Meco实验室将提供连续性、稳定性和详细的科学知识，以实现 NCI资助的拨款。利纳雷斯博士的长期专业知识和奉献精神将促进我们对 CRPC的谱系可塑性有助于设计更有效的治疗方法来克服获得性耐药 前列腺癌。

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.