Renowned Immunologists Join Medical Center

August 01, 2008

Husband-and-wife scientists who are reshaping the frontiers of immunology are among the first high-profile recruits to join the Medical Center as part of the new strategic plan.

Frances Lund, Ph.D., and Troy Randall, Ph.D., are moving their laboratories from the Trudeau Institute in Saranac Lake to the Medical Center. The two have accepted appointments as professors of Medicine in the Division of Allergy/Immunology and Rheumatology, with additional appointments in the Department of Microbiology and Immunology. Their work fits in squarely with the Immunology and Infectious Disease portion of the strategic plan, and also touches upon several additional areas in the plan – cancer, stem cells, and orthopaedics.

Lund and Randall are bringing with them about a dozen scientists, including post-doctoral associates and technicians, who are also making the move from Trudeau to Rochester. The groups are currently setting up new laboratories in the new James P. Wilmot Cancer Center building. The move should be completed by the end of August, with time until then divided between Rochester, the Trudeau Institute, and scientific meetings.

The two immunologists, who met as graduate students in the laboratory of Ronald Corley at Duke, study a variety of areas that have deep routes at the Medical Center. Their work focuses on topics like inflammation and basic B-cell and T-cell biology. Combined, their research touches upon conditions such as flu, bird flu, and other infections; respiratory ailments like asthma; and autoimmune diseases like lupus, rheumatoid arthritis, and diabetes.

“Drs. Lund and Randall are outstanding and well-respected immunologists with the rare ability to move science through all the paces of translational research, including unraveling basic functions, testing them in disease, and generating pre-clinical models to ultimately gain insights into human disease,” said Iñaki Sanz, M.D., head of the Immunology and Infectious Disease portion of the strategic plan and chief of the Division of Allergy/Immunology and Rheumatology within the Department of Medicine. “They will greatly enhance our ability to study a number of human autoimmune and infectious diseases, and we are very fortunate that they have chosen the University as their new home.”

Their extensive research programs in flu extend the Medical Center’s extensive expertise in a disease that kills approximately 30,000 Americans every year. Last year the National Institutes of Health awarded the University $26 million to establish the New York Influenza Center of Excellence to learn more about flu and increase the odds of avoiding a dangerous pandemic caused by bird flu or another dangerous type of flu. The center is headed by David Topham, Ph.D., a leading authority on how our immune system responds to flu, and John Treanor, M.D., who has helped protect people worldwide against flu through the testing of new flu vaccines. University researchers in recent years have taken part in virtually every broad effort by our nation to bolster our defenses against the flu, from testing new vaccines in a pinch to increase supply, to investigating new ways to supply vaccine quickly should a pandemic occur.

Lund is widely known for her work showing that B cells, a key portion of the immune system, do much more than previously thought. While scientists have long recognized that B cells make antibodies that help tag invaders like microbes for destruction, Lund showed less than a decade ago that the cells do much more. She demonstrated that B cells also make chemical signaling molecules known as cytokines that are responsible for much of the messaging that goes on between immune cells. Lund is an expert in sorting out the types of cytokines that B cells make, how they help protect people against infection, their role in infections like strep and tuberculosis, and their role in autoimmune diseases like lupus and rheumatoid arthritis.

“Right now, B cell depletion therapy is being tried for several autoimmune diseases, like rheumatoid arthritis, lupus, multiple sclerosis and diabetes,” said Lund. “But we’re finding out that B cells do a lot of things. By understanding more about B cells, it might be possible to better target potential therapies and develop better treatments.”

Lund is also an expert on the chemical signals that determine how and when inflammatory cells go to sites of infection and tissue damage. She discovered a master regulator of signaling molecules known as chemokines. While researchers around the world are focusing on the effects of knocking out specific chemokines, such as RANTES or MCP-1, Lund is looking at the possibility of targeting the master regulator, CD38, to control several chemokines simultaneously. The molecule plays a key rule regulating the trafficking of immune cells like neutrophils, monocytes, and dendritic cells to sites of inflammation and infection. The work is relevant to a broad array of infections and autoimmune diseases and to the medical issues faced by transplant patients.

Understanding the inflammatory process is crucial to fighting bird flu, another interest of Lund’s. Bird flu is a quick killer whose victims can die within 24 hours, apparently because the lungs simply become swamped with immune cells like macrophages, monocytes and neutrophils that are trying to fend off the infection. Understanding what guides such cells to make such a vigorous early response could help scientists like Lund make the infection a bit less deadly. She has discovered, for instance, that the lungs maintain a reservoir of memory B cells that keep an organism primed to fight off the flu, an unexpected finding that could help shape a future flu vaccine.

Developing a better response against flu is also under scrutiny in Randall’s laboratory. He’s looking at processes that could address a major pain in the arm for millions of people each year. Currently the flu vaccine targets two proteins that change continually; that’s why, every year, people line up for a new flu shot. Randall is looking at targeting proteins in the flu virus that stay steady year to year, opening up the door to a single flu shot that would offer protection for several types of influenza virus. Randall has some promising results showing that while such an approach doesn’t stop the flu completely, it weakens its impact dramatically. He’s also exploring options for completely making the flu “shot” a thing of the past, by looking at the immune reactions that are unique to a flu vaccine given as a nasal spray. The work is part of broad research by Randall on respiratory pathogens and infections.

Randall is also widely known for his research on structures that are very much like lymph nodes and spring up in the lungs, liver, brains, and other organs of some ill people. These are all very surprising places to find structures like lymph nodes.

“A lot of people think of lymph nodes simply as bags of B-cells and T-cells,” said Randall, “but really, these are very sophisticated, highly organized structures. And surprisingly, we’ve found them in several types of tissue. The questions now are, what are they doing there, and can we take advantage of them to improve human health?”

Physicians have been aware for years that such structures are visible on images of lungs of ill patients. But it was Randall who first realized that the structures are very much like lymph nodes, even though they’re directly in organ tissue and not where lymph nodes typically are found. Randall named the structures in the lungs inducible Bronchus-Associated Lymphoid Tissue or iBALT.

In one experiment, Randall’s team made knockout mice that had no conventional lymph nodes, but did have iBALT structures in the lungs. The mice not only fended off the flu, they did so with particular vigor, fighting off levels of the virus that are normally lethal. The work shows the power and potential of the iBALT structures in fighting disease, said Randall, whose team has noted such structures in the pancreas affected by diabetes, the brain affected by multiple sclerosis, and in other organs. Doctors have long noted such structures in the lungs of patients who get severe rheumatoid arthritis.

Like lymph nodes, the structures are likely vital in establishing the body’s ability to recognize friend from foe, playing the role of host for a molecular mixer of sort, where cells exchange vital information about other cells and about foreign invaders.

“These structures are extremely well organized, like lymph nodes,” said Randall. “It’s important to learn about them so we can try to enhance their activity when desired, such as when a patient is fighting an infection, or inhibit their activity, such as in someone who has a chronic disease like asthma.”

Lund and Randall bring with them a great deal of funding, including a combination of five RO1 grants from the National Institutes of Health as well as funding from biotech and pharmaceutical companies. They’ve been at the Trudeau Institute in Saranac Lake, about 100 miles north of Syracuse, since 1997. They’ve also served as adjunct faculty members at the University of Vermont and Albany Medical College.

“We may be the only people whose move to Rochester includes a move to a warmer clime,” joked Randall.

Researchers with whom the couple is discussing collaborations include Sanz, Topham and Treanor; rheumatologists R. John Looney, M.D. and Jennifer Anolik, M.D., Ph.D.; Eddie Schwarz, Ph.D., professor of orthopaedics; and Steve Georas, M.D., chair of the Division of Pulmonary and Critical Care. In the cancer realm, Lund plans to explore how inflammation can be enhanced to respond to and fight off tumors and metastases, and Randall will look at the effects of lymph node-like structures on tumors.

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