Andrea Ventura

Andrea Ventura is a leading cancer biologist at Memorial Sloan Kettering Cancer Center whose research has defined the in vivo functions of microRNAs in cancer using sophisticated mouse genetics, CRISPR-based functional genomics, and translational approaches to miRNA restoration therapy. His work has clarified which microRNAs are bona fide tumor suppressors and how their loss contributes causally to cancer initiation and progression. Ventura's foundational contribution was the development of conditional and inducible microRNA knockout and knockin alleles in mice using homologous recombination and later CRISPR-Cas9 engineering. These genetic tools enabled, for the first time, rigorous in vivo dissection of individual miRNA functions during tumor development, bypassing the limitations of cell-based overexpression studies and transient inhibitor experiments that had dominated the early miRNA cancer field. Using these conditional alleles, Ventura's group provided definitive genetic evidence that the miR-34 family functions as a genuine tumor suppressor in vivo. Mice with germline or conditional deletion of miR-34a/b/c in specific tissue compartments develop tumors at accelerated rates, and miR-34 loss cooperates with other oncogenic events (p53 loss, Kras activation) to drive aggressive malignancy. This genetic validation provided the clearest in vivo demonstration that a microRNA can function as a bona fide tumor suppressor, motivating the clinical miR-34a replacement therapy program. Ventura has also explored miRNA restoration as a cancer therapeutic strategy. His group engineered adeno-associated virus (AAV) vectors expressing tumor suppressor miRNA mimics and demonstrated durable, tissue-specific miRNA restoration that suppresses tumor growth in mouse models of lung and liver cancer. The use of AAV-miRNA as a gene therapy vector offers potential advantages over synthetic miRNA mimics in terms of duration and tissue specificity. Beyond miR-34, Ventura's laboratory has used CRISPR-based forward genetic screens to systematically identify microRNAs that function as tumor suppressors or oncomiRs in specific cancer contexts including lymphoma, lung adenocarcinoma, and hepatocellular carcinoma. His group developed "miRNA sponge" alleles at endogenous loci to study miRNA function through competitive endogenous RNA inhibition, and has characterized how miRNA circuit rewiring contributes to tumor evolution and therapy resistance.

Andrea Ventura 是纪念斯隆-凯特琳癌症中心的领军癌症生物学家，他利用精密小鼠遗传学、CRISPR 功能基因组学和 miRNA 恢复疗法的转化方法，定义了 microRNA 在癌症中的体内功能，厘清了哪些 microRNA 是真正的肿瘤抑制因子。 他的基础性贡献是开发了可条件性和可诱导的 microRNA 敲除/敲入等位基因小鼠，首次实现了对个体 miRNA 在肿瘤发育中功能的严格体内解析。他的团队提供了 miR-34 家族在体内作为真正肿瘤抑制因子的确定性遗传证据，并探索了利用 AAV 载体递送肿瘤抑制 miRNA 模拟物的基因治疗策略。他还利用基于 CRISPR 的正向遗传筛选系统性鉴定了多种癌症背景下的肿瘤抑制性 miRNA 和促癌 miRNA。