Daniel K. Ludwig Professor for Cancer Research
KI Research Areas of Focus:
"Our laboratory is interested in understanding the mechanisms underlying metastasis, the spread of tumor cells throughout the body. We are particularly involved in studying the role of the extracellular matrix, a meshwork of proteins that surrounds both normal and tumor cells and plays many important roles in tumor progression.”
Professor Hynes is Daniel K. Ludwig Professor for Cancer Research at MIT. He received his bachelor's degree in biochemistry from the University of Cambridge, and his doctorate in biology from MIT. After postdoctoral work at the Imperial Cancer Research Fund in London, where he initiated his work on cell adhesion, he returned to MIT as a faculty member. Hynes is a Fellow of the Royal Society of London, the American Academy of Arts and Sciences, the American Association for the Advancement of Science, AACR and ASCB and a member of the US National Academies of Sciences and Medicine. He received the Canada Gairdner International Award, the Pasarow Foundation Medical Research Award, the Benditt Award from the North American Vascular Biology Organization, the E.B. Wilson Medal from the American Society for Cell Biology (ASCB) and the David Rall medal from NAM. He previously headed MIT’s Biology Department, and served as Director of the MIT Center for Cancer Research. He co-chaired the NAS Committees on Human Embryonic Stem Cells and on Human Genome Editing. He is currently on the Cold Spring Harbor Cancer Center Advisory Committee, the MGH Executive Committee on Research and the Rosenstiel Award Selection Committee. Dr. Hynes serves on the Scientific Resource Board of Genentech, the Research Trends and Emerging Technologies Advisory Board of Amgen, and the Scientific Advisory Board of Blade Therapeutics.
Most cells in the body adhere to their neighbors and to the extracellular matrix (ECM), a fibrillar meshwork surrounding or underlying most cells in the body. Cell adhesion plays important roles in the normal functions of cells, contributing to cellular organization and structure, proliferation and survival, and gene expression. Appropriate cell adhesion is necessary for numerous physiological processes and can be perturbed in many diseases, including cancer. The Hynes laboratory seeks to understand the proteins involved in cell-ECM adhesion and the ways in which they control adhesion and migration of cells in both normal and pathological processes.
A major focus of the Hynes lab is cancer, a disease in which cell adhesion plays many important roles. Researchers in the Hynes group are particularly interested in understanding the mechanisms that control the metastatic spread of cancer cells throughout the body and the multiple functions of the ECM during cancer progression. The team is investigating changes in the tumor cells themselves and in their surrounding microenvironment, or niche, which includes both normal cells and the ECM. The matrix changes extensively during tumor progression and metastasis, and the Hynes lab is playing a leading role in analyzing these changes using proteomic methods, which reveal the full collection of proteins involved. Extracellular matrix (ECM) constitutes an important part of the microenvironment of tumor cells, providing signals for their growth and survival and also contributing to the development of resistance to radio- and chemo-therapy. This resistance is one of the challenging aspects of cancer therapy.
In recent work the laboratory has developed nanobodies to ECM proteins elevated in the metastatic niche and shown their effectiveness in selectively imaging tumors, including early lesions and metastases using PET/CT and other imaging methods. This selective targeting of tumor ECM can also be used to deliver therapeutic agents to tumors and metastases, including CAR T cells that promote an immune response to solid tumors. These approaches offer promise for clinical applications.
For more information about Professor Hynes's research, please visit the Hynes lab webpage.
Rickelt S, Condon C, Mana M, Whittaker CA, Pfirschke C, Roper J, Patil D, Brown I, Mattia AR, Zukerberg L, Zhao QG, Chetty R, Lauwers G, Leijssen G, Nejaz A, Boylan K, Yilmaz OH, Deshpande V, Hynes RO. 2020. Agrin in the Muscularis Mucosa Serves as a Biomarker Distinguishing Hyperplastic Polyps from Sessile Serrated Lesions. Clin. Cancer Res. 26:1277-1287.
Hebert JD, Myers SA, Naba A, Abbruzzese G, Lamar JM, Carr SA, Hynes RO. 2020. Proteomic profiling of the ECM of xenograft breast cancer metastases in different organs reveals distinct metastatic niches. Cancer Res. 80:1475-1485.
Tian C, Öhlund D, Rickelt S, Lidström T, Huang Y, Hao L, Zhao RT, Franklin O, Bhatia SN, Tuveson DA, Hynes RO. 2020. Cancer-cell-derived matrisome proteins promote metastasis in pancreatic ductal adenocarcinoma. Cancer Res. 80:1461-1474.
Hebert JD, Tian C, Lamar JM, Rickelt S Abbruzzese, G Liu, X, Hynes RO. 2020. The scaffold protein IQGAP1 is crucial for extravasation and metastasis. Sci Rep. 10:2439.
Tian C, Clauser K, Öhlund D, Rickelt S, Huang Y, Gupta M, Mani DR, Carr SA, Tuveson DA, Hynes RO. 2019. Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveals different contributions by tumor and stromal cells. Proc Natl Acad Sci U S A. 116:19609-19618.
Jailkhani N, Ingram JR, Rashidian M, Rickelt S, Tian C, Mak H, Jiang Z, Ploegh H, Hynes RO. 2019. Noninvasive imaging of tumor progression, metastasis, and fibrosis using a nanobody targeting the extracellular matrix. Proc Natl Acad Sci U S A. 116:14181-14190.
Xie J, Dougan M, Jailkhani N, Ingram JR, Fang T, Kummer L, Momin N, Pishesha N, Rickelt S, Hynes RO, Ploegh H. 2019. Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Proc Natl Acad Sci U S A. 116:7624-7631
Lamar JM, Xiao Y, Norton E, Jiang ZG, Gerhard GM, Kooner S, Warren JSA, Hynes RO. 2018. Src tyrosine kinase activates the YAP/TAZ axis and thereby drives tumor growth and metastasis. J. Biol. Chem. 294:2302-2317.
Naba A, Clauser KR, Ding H, Whittaker CA, Carr SA, Hynes, RO. 2016. The extracellular matrix: tools and insights for the “omics” era. Matrix Biol. 49: 10-24.
Labelle M, Begum S, Hynes RO. 2014. Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci USA 111: E3053-3061.
Hynes RO. 2009. The Extracellular Matrix: not just pretty fibrils. Science 326: 1216-1219.