Tyler Jacks

Tyler Jacks is one of the world's foremost cancer geneticists and a pioneer in the development of genetically engineered mouse models (GEMMs) that faithfully recapitulate human cancers. As Director of the MIT Koch Institute for Integrative Cancer Research for 14 years, he led one of the world's most productive cancer research institutions and helped define the modern intersection of cancer biology and engineering. Jacks trained with Harold Varmus and Robert Weinberg before establishing his own laboratory at MIT, where his research has focused on two intertwined areas: understanding the biology of tumor suppressor genes and building mouse models that mirror the genetic and histological characteristics of human cancer. In the early 1990s, his laboratory created knockout mice lacking the retinoblastoma tumor suppressor (Rb), demonstrating that Rb loss leads to ectopic cell proliferation and apoptosis — validating the two-hit model of tumor suppressor inactivation in vivo. His group was among the first to create conditional mouse models of lung cancer using the Cre-lox recombination system. By inserting loxP sites flanking the endogenous Kras locus and combining it with conditional p53 deletion, Jacks generated the KrasLSL-G12D; p53fl/fl mouse — still the most widely used autochthonous model of human lung adenocarcinoma. This approach demonstrated that activation of mutant Kras combined with p53 loss faithfully reproduces the histology, metastatic potential, and drug response patterns seen in human lung adenocarcinoma patients. Jacks made major contributions to understanding p53 tumor suppressor biology, showing how p53 acts as a guardian of the genome by integrating DNA damage signals, oncogene activation, and metabolic stress to drive cell cycle arrest or apoptosis. His laboratory revealed the roles of p53 target genes (including PUMA, NOXA, and p21) in dictating the cellular outcome of p53 activation, and explored how partial restoration of p53 function in established tumors can cause dramatic tumor regression. Beyond lung cancer, Jacks' laboratory has made major contributions to understanding the biology of mesothelioma, lymphoma, and pancreatic cancer using analogous conditional GEMM approaches. He is also a Howard Hughes Medical Institute Investigator and a member of the National Academy of Sciences.

Tyler Jacks 是世界上最重要的癌症遗传学家之一，也是开发忠实重现人类癌症的基因工程小鼠模型的先驱。在担任麻省理工学院科赫综合癌症研究所所长的14年间，他领导了世界上最富成效的癌症研究机构之一。 他的实验室开发了条件性肺癌小鼠模型，通过Cre-lox重组系统，生成了KrasLSL-G12D; p53fl/fl小鼠——迄今为止使用最广泛的人类肺腺癌内源性模型。他在p53肿瘤抑制因子生物学方面做出了重要贡献，阐明了p53如何整合DNA损伤信号以驱动细胞周期阻滞或凋亡。