The molecular glue that holds the body's cells together literally holds us together. Without it, we humans would be a pile of cells on the floor, hardly human at all. For three decades, Richard O. Hynes has worked to uncover the specific proteins that govern the way cells stick to each other, a phenomenon known as cell adhesion. This "glue of life" also helps to ensure that when cells move, they go to their proper locations and stay there. Defects in cell adhesion underlie many diseases, including cancer, inflammation, and thrombosis, a potentially fatal condition that occurs when a blood clot in a vein breaks loose and travels to the lungs, heart, or brain, obstructing blood flow. By studying the way cells stick together and migrate in both healthy and disease states, Hynes hopes his research will lay the foundation for scientists to develop new therapies for adhesion-related disorders.
From his childhood in Great Britain, Hynes gravitated toward science. His father was a freshwater ecologist and his mother a college physics teacher, and they instilled in their son a scientist's inquisitive attitude. This curiosity was nurtured by the British school system, which encouraged students to select a broad focus of study beginning at age 11. Hynes naturally chose science and has never looked back. "Science is intellectually exciting and entertaining, and the boundary between work and hobby is hard to define," he noted. "It's good to be employed to play at what you like to do."
As a postdoctoral student at the Imperial Cancer Research Fund in England, Hynes was investigating the molecular changes on cell surfaces that distinguish cancer cells from normal cells when he discovered fibronectin. This structural protein was present on normal cells but noticeably absent on cancer cells. Hynes's discovery set into motion a string of studies that has helped to establish cell adhesion as its own field of investigation. "Cell adhesion is essential for life in all organisms made up of more than one cell," Hynes explained. "It is what determines where cells are in the body, how they interact with one another, and how and where they move, both during embryonic development and in normal physiology."
Hynes's studies also uncovered integrins, a family of protein receptors that gives cells their stickiness by binding with fibronectin and other cell adhesion molecules. By forming a physical link between the extracellular environment and the cell's interior, integrins help to control cell shape and movement as well as accurate cell adhesion through the transmission of signals into and out of cells. For example, white blood cells must stick in the appropriate places to fight off infection, but inflammation is the result if they adhere at the wrong place or time.
Many of Hynes's current research projects are aimed at studying cell adhesion by developing mice that lack genes that code for adhesion proteins and evaluating their effects on the animals. Many of the mutations have been linked to errors in the development of new blood vessels, which require proper cell adhesion and migration to grow normally. Hynes is also applying his understanding of cell adhesion to the study of cancer. Missteps in cell adhesion are known to be involved in tumor invasion, metastasis, and other aspects of cancer progression. Additionally, Hynes is investigating the relationship among fibronectins, integrins, and their cytoskeletal connections by studying their interactions in cell culture, which allows a more detailed analysis than animal studies. This in-depth understanding is vital to the development of drugs that block cell adhesion.
Dr. Hynes is also Daniel K. Ludwig Professor for Cancer Research at the Massachusetts Institute of Technology.
RESEARCH ABSTRACT SUMMARY:
Richard Hynes is interested in understanding the mechanisms underlying metastasis, the spread of tumor cells throughout the body. His laboratory is particularly involved in studying the role of the extracellular matrix, a fibrillar meshwork of proteins that surrounds both normal and tumor cells and plays many important roles in tumor progression. They are also interested in the contributions of normal cells; platelets, leukocytes and blood vessels, both in metastasis and in other body functions.
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