Molecular mechanisms driving therapy-induced lineage plasticity

总结 该提案寻求Juan弗朗西斯科Linares博士作为研究专家的工资，以支持Maria T. Diaz-Meco在Weill Cornell医学病理学和实验室医学系的研究项目 研究调节前列腺癌谱系可塑性的分子和细胞机制。的 阐明去势抵抗性前列腺癌细胞（CRPC）用于逃避 治疗压力要求科学家对这一过程的分子生物学有深入的了解， 而且还具有忠实地再现人类疾病的体内小鼠模型所需的技术专长， 以及进行严格的表观遗传分析所必需的生物信息学工具。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。他在以下方面做出了开创性的贡献： 信号，炎症，代谢和癌症，并具有坚实的跨学科培训，这将是至关重要的 项目的成功。他将致力于研究计划，重点是定义分子和细胞 促使CRPC分化为更具侵袭性的前列腺癌变体的机制，例如 神经内分泌和间质前列腺癌。凭借他在癌症生物学和癌症代谢方面的专业知识 和他应用新型小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， Diaz-Meco实验室将提供连续性，稳定性和详细的科学知识，以实现以下目标： 国家癌症研究所资助的赠款金Linares博士的长期专业知识和奉献精神将促进我们对 CRPC中的谱系可塑性，以帮助设计更有效的治疗方法，以克服CRPC中的获得性耐药性。 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.