Richard Hynes, a pioneer in the biology of cellular adhesion, dies at 81

MIT Professor Emeritus Richard O. Hynes PhD '71, a cancer biologist whose discoveries reshaped modern understandings of how cells interact with each other and their environment, passed away on Jan. 6. He was 81.

Hynes is best known for his discovery of integrins, a family of cell-surface receptors essential to cell-cell and cell-matrix adhesion. He played a critical role in establishing the field of cell adhesion biology, and his continuing research revealed mechanisms central to embryonic development, tissue integrity, and diseases including cancer, fibrosis, thrombosis, and immune disorders.

Hynes was the Daniel K. Ludwig Professor for Cancer Research, Emeritus, an emeritus professor of biology, and a member of the Koch Institute for Integrated Cancer Research at MIT and the Broad Institute of MIT and Harvard. During his more than 50 years on the faculty at MIT, he was deeply respected for his academic leadership at the Institute and internationally, as well as his intellectual rigor and contributions as an educator and mentor.

"Richard had an enormous impact in his career. He was a visionary leader of the MIT Cancer Center, what is now the Koch Institute, during a time when the progress in understanding cancer was just starting to be translated into new therapies," reflects Matthew Vander Heiden, director of the Koch Institute and the Lester Wolfe (1919) Professor of Molecular Biology. "The research from his laboratory launched an entirely new field by defining the molecules that mediate interactions between cells and between cells and their environment. This laid the groundwork for better understanding the immune system and metastasis."

Pond skipper

Born in Kenya, Hynes grew up during the 1950s in Liverpool, in the United Kingdom. While he sometimes recounted stories of being schoolmates with two of the Beatles, and in the same Boy Scouts troop as Paul McCartney, his academic interests were quite different, and he specialized in the sciences at a young age. Both of his parents were scientists: His father was a freshwater ecologist, and his mother a physics teacher. Hynes and all three of his siblings followed their parents into scientific fields.

"We talked science at home, and if we asked questions, we got questions back, not answers. So that conditioned me into being a scientist, for sure," Hynes said of his youth.

He described his time as an undergraduate and master's student at Cambridge University during the 1960s as "just fantastic," noting that it was shortly after two 1962 Nobel Prizes were awarded to Cambridge researchers - one to Francis Crick and James Watson for the structure of DNA, the other to John Kendrew and Max Perutz for the structures of proteins - and Cambridge was "the place to be" to study biology.

Newly married, Hynes and his wife traded Cambridge, U.K. for Cambridge, Massachusetts, so that he could conduct doctoral work at MIT under the direction of Paul Gross. He tried (and by his own assessment, failed) to differentiate maternal messages among the three germ layers of sea urchin embryos. However, he did make early successful attempts to isolate the globular protein tubulin, a building block for essential cellular structures, from sea urchins.

Inspired by a course he had taken with Watson in the United States, Hynes began work during his postdoc at the Institute of Cancer Research in the U.K. on the early steps of oncogenic transformation and the role of cell migration and adhesion; it was here that he made his earliest discovery and characterizations of the fibronectin protein.

Recruited back to MIT by Salvador Luria, founding director of the MIT Center for Cancer Research, whom he had met during a summer at Woods Hole Oceanographic Institute on Cape Cod, Hynes returned to the Institute in 1975 as a founding faculty member of the center and an assistant professor in the Department of Biology.

Big questions about tiny cells

To his own research, Hynes brought the same spirit of inquiry that had characterized his upbringing, asking fundamental questions: How do cells interact with each other? How do they stick together to form tissues?

His research focused on proteins that allow cells to adhere to each other and to the extracellular matrix - a mesh-like network that surrounds cells, providing structural support, as well as biochemical and mechanical cues from the local microenvironment. These proteins include integrins, a type of cell surface receptor, and fibronectins, a family of extracellular adhesive proteins. Integrins are the major adhesion receptors connecting the extracellular matrix to the intracellular cytoskeleton, or main architectural support within the cell.

Hynes began his career as a developmental biologist, studying how cells move to the correct locations during embryonic development. During this stage of development, proper modulation of cell adhesion is critical for cells to move to the correct locations in the embryo.

Hynes' work also revealed that dysregulation of cell-to-matrix contact plays an important role in cancer cells' ability to detach from a tumor and spread to other parts of the body, key steps in metastasis.

As a postdoc, Hynes had begun studying the differences in the surface landscapes of healthy cells and tumor cells. It was this work that led to the discovery of fibronectin, which is often lost when cells become cancerous.

He and others found that fibronectin is an important part of the extracellular matrix. When fibronectin is lost, cancer cells can more easily free themselves from their original location and metastasize to other sites in the body. By studying how fibronectin normally interacts with cells, Hynes and others discovered a family of cell surface receptors known as integrins, which function as important physical links with the extracellular matrix. In humans, 24 integrin proteins have been identified. These proteins help give tissues their structure, enable blood to clot, and are essential for embryonic development.

"Richard's discoveries, along with others', of cell surface integrins led to the development of a number of life-altering treatments. Among these are treatment of autoimmune diseases such as multiple sclerosis," notes longtime colleague Phillip Sharp, MIT Institute professor emeritus.

As research technologies advanced, including proteomic and extracellular matrix isolation methods developed directly in Hynes' laboratory, he and his group were able to uncover increasingly detailed information about specific cell adhesion proteins, the biological mechanisms by which they operate, and the roles they play in normal biology and disease.

In cancer, their work helped to uncover how cell adhesion (and the loss thereof) and the extracellular matrix contribute not only to fundamental early steps in the metastatic process, but also tumor progression, therapeutic response, and patient prognosis. This included studies that mapped matrix protein signatures associated with cancer and non-cancer cells and tissues, followed by investigations into how differentially expressed matrix proteins can promote or suppress cancer progression.

Hynes and his colleagues also demonstrated how extracellular matrix composition can influence immunotherapy, such as the importance of a family of cell adhesion proteins called selectins for recruiting natural killer cells to tumors. Further, Hynes revealed links between fibronectin, integrins, and other matrix proteins with tumor angiogenesis, or blood vessel development, and also showed how interaction with platelets can stimulate tumor cells to remodel the extracellular matrix to support invasion and metastasis. In pursuing these insights into the oncogenic mechanisms of matrix proteins, Hynes and members of his laboratory have identified useful diagnostic and prognostic biomarkers, as well as therapeutic targets.

Along the way, Hynes shaped not only the research field, but also the careers of generations of trainees.

"There was much to emulate in Richard's gentle, patient, and generous approach to mentorship. He centered the goals and interests of his trainees, fostered an inclusive and intellectually rigorous environment, and cared deeply about the well-being of his lab members. Richard was a role model for integrity in both personal and professional interactions and set high expectations for intellectual excellence," recalls Noor Jailkhani, a former Hynes Lab postdoc.

Jailkhani is CEO and co-founder, with Hynes, of Matrisome Bio, a biotech company developing first-in-class targeted therapies for cancer and fibrosis by leveraging the extracellular matrix. "The impact of his long and distinguished scientific career was magnified through the generations of trainees he mentored, whose influence spans academia and the biotechnology industry worldwide. I believe that his dedication to mentorship stands among his most far-reaching and enduring contributions," she says.

A guiding light

Widely sought for his guidance, Hynes served in a number of key roles at MIT and in the broader scientific community. As head of MIT's Department of Biology from 1989 to 1991, then a decade as director of the MIT Center for Cancer Research, his leadership has helped shape the Institute's programs in both areas.

"Words can't capture what a fabulous human being Richard was. I left every interaction with him with new insights and the warm glow that comes from a good conversation," says Amy Keating, the Jay A. Stein (1968) Professor, professor of biology and biological engineering, and head of the Department of Biology. "Richard was happy to share stories, perspectives, and advice, always with a twinkle in his eye that conveyed his infinite interest in and delight with science, scientists, and life itself. The calm support that he offered me, during my years as department head, meant a lot and helped me do my job with confidence."

Hynes served as director of the MIT Center for Cancer Research from 1991 until 2001, positioning the center's distinguished cancer biology program for expansion into its current, interdisciplinary research model as MIT's Koch Institute for Integrative Cancer Research. "He recruited and strongly supported Tyler Jacks to the faculty, who subsequently became director and headed efforts to establish the Koch Institute," recalls Sharp.

Jacks, a David H. Koch (1962) Professor of Biology and founding director of the Koch Institute, remembers Hynes as a thoughtful, caring, and highly effective leader in the Center for Cancer Research, or CCR, and in the Department of Biology. "I was fortunate to be able to lean on him when I took over as CCR director. He encouraged me to drop in - unannounced - with questions and concerns, which I did regularly. I learned a great deal from Richard, at every level," he says.

Hynes' leadership and recognition extended well beyond MIT to national and international contexts, helping to shape policy and strengthen connections between MIT researchers and the wider field. He served as a scientific governor of the Wellcome Trust, a global health research and advocacy foundation based in the United Kingdom, and co-chaired U.S. National Academy committees establishing guidelines for stem cell and genome editing research.

"Richard was an esteemed scientist, a stimulating colleague, a beloved mentor, a role model, and to me a partner in many endeavors both within and beyond MIT," notes H. Robert Horvitz, a David H. Koch (1962) Professor of Biology. He was a wonderful human being, and a good friend. I am sad beyond words at his passing."

Awarded Howard Hughes medical investigator status in 1988, Hynes' research and leadership have since been recognized with a number of other notable honors. Most recently, he received the 2022 Albert Lasker Basic Medical Research Award, which he shared with Erkki Ruoslahti of Sanford Burnham Prebys and Timothy Springer of Harvard University, for his discovery of integrins and pioneering work in cell adhesion.

His other awards include the Canada Gairdner International Award, the Distinguished Investigator Award from the International Society for Matrix Biology, the Robert and Claire Pasarow Medical Research Award, the E.B. Wilson Medal from the American Society for Cell Biology, the David Rall Medal from the National Academy of Medicine and the Paget-Ewing Award from the Metastasis Research Society. Hynes was a member of the National Academy of Sciences, the National Academy of Medicine, the Royal Society of London, the American Association for the Advancement of Science, and the American Academy of Arts and Sciences.

Easily recognized by a commanding stature that belied his soft-spoken nature, Hynes was known around MIT's campus not only for his acuity, integrity, and wise counsel, but also for his community spirit and service. From serving food at community socials to moderating events and meetings or recognizing the success of colleagues and trainees, his willingness to help spanned roles of every size.

"Richard was a phenomenal friend and colleague. He approached complex problems with a thoughtfulness and clarity that few can achieve," notes Vander Heiden. "He was also so generous in his willingness to provide help and advice, and did so with a genuine kindness that was appreciated by everyone."

Hynes is survived by his wife Fleur, their sons Hugh and Colin and their partners, and four grandchildren.