David H. Koch (1962) Professor of Biology
Daniel K. Ludwig Scholar
Co-director, Ludwig Center at MIT
"The Jacks laboratory is interested in the genetic events contributing to the development of cancer. The focus of our research has been a series of mouse models engineered to carry mutations in genes known to be involved in human cancer."
Professor Jacks received his bachelor's degree in biology from Harvard College, and his doctorate from the University of California, San Francisco, where he trained with Nobel Laureate Harold Varmus. He was a postdoctoral fellow with Robert Weinberg at the Whitehead Institute before he joined the MIT faculty in 1992. From 2001-2021, Professor Jacks served as Director of the MIT Center for Cancer Research and its successor, the Koch Institute at MIT. He was also a Howard Hughes Medical Institute Investigator from 1994-2021 and resigned his HHMI position to take his current role as President of Break Through Cancer. In recognition of his contributions to the study of cancer genetics, Professor Jacks received the AACR Outstanding Achievement Award, the Amgen Award from the American Society of Biochemistry and Molecular Biology, the Paul Marks Prize for Cancer Research, and the Sergio Lombroso Award in Cancer Research. He also served as Chair of the National Cancer Advisory Board at the National Cancer Institute, was a member of the Board of Directors of the American Association for Cancer Research (AACR), and was elected President of the AACR in 2009. Professor Jacks was also elected to the National Academy of Sciences, the Institute of Medicine of the National Academies, the American Academy of Arts and Sciences, and the inaugural class of Fellows of the AACR Academy. In 2015, he was the recipient of the Killian Award, the highest honor the MIT faculty can bestow upon one of its members, and in 2020 he was recognized with the AACR Princess Takamatsu Memorial Lectureship. Professor Jacks serves on the Board of Directors of Thermo Fisher Scientific and Amgen, and is also a co-founder of T2 Biosystems and Dragonfly Therapeutics as well as a scientific advisor to Skyhawk Therapeutics, SQZ Biotech, and the Lustgarten Foundation.
The Jacks laboratory studies the genetic events underlying the development of cancer. Professor Jacks has pioneered the use of gene targeting technology in the mouse to study cancer-associated genes and to construct mouse models of many human cancer types, including cancers of the lung, pancreas, colon, and soft tissue. These powerful and sophisticated models closely recapitulate human disease, and have led to novel insights into tumor development, as well as new strategies for cancer detection and treatment. By combining these pre-clinical models with cutting-edge tools in genetics and genomics, the Jacks lab has been able to illuminate the pathways and processes critical for cancer progression.
More recently, the Jacks group has begun using these advanced models to investigate how immune and tumor cells interact during tumor development, and how tumor immune responses affect the development of cancer in mice. Among various aspects of cancer immunology under investigation are two main groups of cells, T cells and NK cells, which play an important role in lung cancer development. Modulating these pathways may prove a viable therapeutic strategy for improving outcomes for patients with lung adenocarcinoma, colon cancer, and pancreas cancer. The group further engineered developing tumors in mouse models of cancer to express model T cell antigens, which serve as targets for tumor-specific T cells and stimulate anti-tumor immune responses. These models offer a unique platform for investigating how anti-tumor immune responses shape tumor gene expression, and importantly how tumor evasion mechanisms contribute to the development of advanced disease. Moreover, they are invaluable preclinical models for testing immunotherapeutics, as single agents, or in combinations with traditional or targeted therapies.
For more information about Professor Jacks's research, please visit the Jacks lab webpage.
Sánchez-Rivera FJ, Ryan J, Soto-Feliciano YM, Clare Beytagh M, Xuan L, Feldser DM, Hemann MT, Zamudio J, Dimitrova N, Letai A, Jacks T. Mitochondrial apoptotic priming is a key determinant of cell fate upon p53 restoration. Proc Natl Acad Sci U A. 2021. 118(23): e2019740118. doi: 10.1073/pnas.2019740118.
LaFave LM, Kartha VK, Ma S, Meli K, Del Priore I, Lareau C, Naranjo S, Westcott PMK, Duarte FM, Sankar V, Chiang Z, Brack A, Law T, Hauck H, Okimoto A, Regev A, Buenrostro JD, Jacks T. Cancer Cell. Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma. 2020. 38(2): 212-228. e13. doi: 10.1016/j.ccell.2020.06.006.
Ng SR, Rideout WM 3rd, Akama-Garren EH, Bhutkar A, Mercer KL, Schenkel JM, Bronson RT, Jacks T. CRISPR-mediated modeling and functional validation of candidate tumor suppressor genes in small cell lung cancer. Proc Natl Acad Sci USA. 2020. 117(1): 513-521. doi: 10.1073/pnas.1821893117. Epub 2019 Dec 23.
Romero R, Sánchez-Rivera FJ, Westcott PMK, Mercer KL, Bhutkar A, Muir A, González Robles TJ, Rodriquez SL, Liao LZ, Ng SR, Li L, Colón CI, Naranjo SN, Beytagh MC, Lewis CA, Hsu PP, Bronson RT, Vander Heiden MG, Jacks T. Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. 2020. Nat Cancer 1: 589–602. doi: 10.1038/s43018-020-0071-1
Li A, Herbst RH, Canner D, Schenkel JM, Smith OC, Kim JY, Hillman M, Bhutkar A, Cuoco MS, Rappazzo CG, Rogers P, Dang C, Jerby-Arnon L, Rozenblatt-Rosen O, Cong L, Birnbaum M, Regev A, Jacks T. Il-33 signaling alters regulatory T cell diversity in support of tumor development. Cell Rep. 2019. 29(10): 2998-3008. e8. doi: 10.1016/j.celrep.2019.10.120.
Li L, Ng SR, Colón CI, Drapkin BJ, Hsu PP, Li Z, Nabel CS, Lewis CA, Romero R, Mercer KL, Bhutkar A, Phat S, Myers DT, Muzumdar MD, Westcott PMK, Beytagh MC, Farago AF, Vander Heiden MG, Dyson NJ, Jacks T. Identification of DHODH as a therapeutic target in small cell lung cancer. Sci Transl Med. 2019. 11(517): pii: eaaw7852. doi: 10.1126/scitranslmed.aaw7852.
Schmidt L, Eskiocak B, Kohn R, Dang C, Joshi NS, DuPage M, Lee DY, Jacks T. Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation. PNAS. 2019. 116(35): 17460-17469.
Jaeger AM, Stopfer L, Lee S, Gaglia G, Sandel D, Santagata S, Lin NU, Trepel JB, White F, Jacks T, Lindquist S, Whitesell L. Rebalancing protein homeostasis enhances tumor antigen presentation. Clin Cancer Res. 2019. 25(21):6392-6405.
Jin C, Lagoudas GK, Zhao C, Bullman S, Bhutkar A, Hu B, Ameh S, Sandel D, Liang XS, Mazzilli S, Whary MT, Meyerson M, Germain R, Blainey PC, Fox JG, Jacks T. 2019. Commensal Microbiota Promote Lung Cancer Development via γδ T Cells. Cell 176(5): 998-1013.
Chen PY, Muzumdar MD, Dorans KJ, Robbins R, Bhutkar A, Del Rosario A, Mertins P, Qiao J, Schafer AC, Gertler F, Carr S, Jacks T. 2018. Adaptive and Reversible Resistance to Kras inhibition in Pancreatic Cancer Cells. Cancer Res 78(4): 985-1002.
Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS, Helenius K, Park Y, Azimi R, Kerper NR, Wesselhoeft RA, et al. 2017. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature 545: 355–359.
Joshi NS, Akama-Garren EH, Lu Y, Lee D-Y, Chang GP, Li A, DuPage M, Tammela T, Kerper NR, Farago AF, et al. 2015. Regulatory T Cells in tumor-associated tertiary lymphoid structures suppress anti-tumor T cell responses. Immunity 43: 579–590.
Sánchez-Rivera FJ, Papagiannakopoulos T, Romero R, Tammela T, Bauer MR, Bhutkar A, Joshi NS, Subbaraj L, Bronson RT, Xue W, et al. 2014. Rapid modelling of cooperating genetic events in cancer through somatic genome editing. Nature 516: 428–431.