Cell Biology, Immunology
Dr. Medzhitov is also the David W. Wallace Professor of Immunobiology at Yale University School of Medicine.
Inflammation, Homeostasis, and Disease
Ruslan Medzhitov is probably best known for the fundamental discoveries he’s made concerning the roles that the immune system’s Toll-like receptors play in controlling adaptive immunity, infections, chronic inflammation, and tumor growth. However, recently he’s turned his attention to other areas of the immune system, such as inflammation, tissue biology, and allergic reaction.
The inflammatory response protects the body from infection and injury and allows it to reestablish a homeostatic state. But inflammation also operates at a cost to other physiological functions. During inflammation the body can become more susceptible to certain diseases. Medzhitov’s research team is trying to learn more about the signals that initiate and control the process of inflammation, as well as the mechanisms responsible for inflammatory diseases.
A related area of study in the Medzhitov lab focuses on tissue biology – including tissue design principles – and the communication circuits that help to establish stable cellular communities within tissues. When these circuits become derailed, a number of degenerative, fibrotic, and neoplastic diseases can result. Of particular interest to the Medzhitov lab are the macrophages and stromal cells that reside in tissues. These two cell types, along with the microvascular endothelium, constitute universal components of vertebrate tissues.
One of the biggest puzzles in current immunology is how and why allergens induce immune responses. Medzhitov’s team is trying to solve this puzzle. Medzhitov believes that allergies are an essential defense mechanism that protects us from noxious substances. The major symptoms of allergic reactions – tears, sneezing, coughing – help expel unwanted agents from the body, while excessive activity of these defenses causes allergic diseases.
Grants from the National Institutes of Health provided partial support for these projects.
In the early 1990s, while a graduate student at Moscow University, Medzhitov stumbled upon a paper that launched his career. Written by Yale immunologist Charles Janeway (an HHMI investigator until his death in 2003), the article sketched a new theory for how the immune system recognizes and responds to pathogens. Janeway’s ideas ignited Medzhitov, sending him to his university’s sole email terminal. “The very first email I ever sent was my message to Charlie, discussing some ideas related to his theory,” says Medzhitov.
“Charlie’s paper made sense of many complicated and confusing problems in immunology at the time,” says Medzhitov. “That was the point I first thought about being a researcher in immunology. As an undergraduate student, I never had a course on immunology.”
After a short student fellowship with Russ Doolittle at the University of California, San Diego, Medzhitov landed a postdoctoral position in Janeway’s lab in early 1994.
When he arrived at Yale – after a detour to Moscow to defend his thesis and sweat out a government coup – Medzhitov felt overwhelmed. “My challenge was, not only did I not speak English well, I also had never done any experiments. In Russia, there was no money to do experimental work. All I could do was sit in the library. So I arrived without any experience. I had to learn as quickly as I could.”
That lack of experience did have its advantages. Janeway’s theory that innate immunity acted by recognizing bits of invading organisms, was “extremely speculative,” and thus risky to work on. Medzhitov, “oblivious to concerns about career,” jumped right in. “I was just happy to be in a place where I could do science,” he says.
In 1996, Janeway and Medzhitov discovered cell surface receptors that triggered the second arm of the immune system – the T cells and B cells that attack pathogens. Studying these proteins, dubbed Toll-like receptors, quickly became one of the hottest areas in biology.
In the two decades since, Medzhitov has made one discovery after another, dramatically expanding our understanding of the roles Toll-like receptors play in infection control, chronic inflammation, and even tumor growth. His research interests now focus on inflammation, allergy, cell communication, and tissue biology.