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Sharon Stranford: Exploring the Mysteries of the Immune System

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For Peter Houlihan, a Day at MHC Is Often a Walk in the Woods

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Mount Holyoke College News and Events Vista The College Street Journal Archives

November 9, 2001

Sharon Stranford: Exploring the Mysteries of the Immune System


FRED LEBLANC

Two San Franciscans are exposed several times to the human immunodeficiency virus (HIV), but only one becomes infected. Two others, already HIV positive, show equally puzzling differences over the years; one rapidly deteriorates and develops acquired immunodeficiency syndrome (AIDS), while the other lives in excellent health. From 1995 to 1999, Sharon Stranford and Jay Levy of the University of California, San Francisco (UCSF), studied such cases, trying to uncover why some individuals resist AIDS while others do not. Levy, among the first to isolate human strains of HIV in the United States, continues the investigation at UCSF with a large group of patient volunteers and research collaborators. Stranford continues it through research and teaching at Mount Holyoke, where she is now Clare Boothe Luce Assistant Professor of Biology.

"They are engaged and curious," said Stranford of the students enrolled in her fall course Introduction to Immunology. "Many of them want to go on to medical school or graduate programs in biomedicine or infectious disease, so they encouraged me to focus on human diseases. I'm lucky to be able to teach the same subject of my interest and research."

Stranford's interest in disease and immunity began even before her undergraduate days at Pennsylvania's Beaver College (now Arcadia University). It emerged in high school, when she learned that her friend's mother suffered from the autoimmune disease lupus, then witnessed firsthand the potentially strange outcomes of an immune response. The strange things that Stranford witnessed in her youth she now understands to be the result of an immune system unable to differentiate viruses and bacteria from healthy cells and tissues, a system that no longer protects the body from sickness but actually attacks it and leads to painful diseases like lupus and multiple sclerosis.

Studying these diseases in the context of immunology and modern microbiology was uncommon at the undergraduate level in Stranford's day, but she remained intrigued by the few immunology lectures offered in her biology courses. She went on to study immunology, molecular biology, and genetics at Hahnemann University in Philadelphia, focusing her doctoral work on the genetic blueprint of two groups of rats, one susceptible to a disease akin to multiple sclerosis, the other resistant to it.

The flip side of that research came next for Stranford, as she spent three years at Oxford University—focusing not on how to protect the immune system from disease, but on how to fool it into tolerance for something it would normally attack: a foreign graft or organ. "It was a highly practical study," said Stranford, "because it is very difficult to find an exact match for skin grafts or organ transplants." We already know about a phenomenon called "the blood transfusion effect," she said, whereby people more readily accept transplanted organs if they first receive blood from the organ donor. Stranford set about studying mice to see just how this trickery of the immune system worked.

Before transplanting a foreign heart into a recipient mouse, Stranford mixed new genes from the donor mouse into cells of the recipient, then let them spread through the mouse's body so that they might "re-educate" the immune system to tolerate the foreign heart. The research not only helped Stranford hone in on which DNA and proteins can help re-educate the immune system but also led her to a new research interest— studies of RNA-containing viruses (such as HIV), called "retroviruses." Having used retroviruses to transfer new DNA into the cells of host mice, and having seen the way that retroviruses can sometimes induce a disease that wreaks havoc on the immune system (and ultimately causes immune deficiency), Stranford shifted her work from heart transplants and immune tolerance to HIV and AIDS.

This new interest first brought Stranford to California for postdoctoral work with Levy, then on to a teaching position at Amherst College, where she moved to studying a mouse version of AIDS called MAIDS. This time, she looked at the genetic differences between two mouse strains that differ in their vulnerability to MAIDS—similar in its symptoms to human AIDS.

Stranford is continuing this research at Mount Holyoke. In particular, she is studying the white blood cells known as CD8+ T cells; these cells can be activated to "see" viruses living inside host cells and either kill those cells or suppress the virus they carry. This particular ability of CD8+ cells was found to be prevalent in some high-risk populations in San Francisco, Stranford explains. In many of the people she studied who had "beat the odds" of HIV infection, the CD8+ cells appeared to have multiplied and become very active after a first exposure to the virus. This activity itself was not surprising—we count on similar immune responses when we give babies a small dose of mumps and measles in a vaccine—but just how and why those CD8+ cells worked so well in some people and not others is unknown.

Stranford hopes to find out. She hypothesizes that mice proven to be genetically resistant to MAIDS will have a different type of CD8+ cell response than susceptible mice. By breaking open the CD8+ cells of virus-resistant mice, Stranford hopes to learn exactly what proteins they are producing and secreting and whether those secretions interfere with the life cycle of the virus. If successful, Stranford hopes to use this information to help others like Levy pinpoint how CD8+ cells might be working against HIV infections in some people.

"HIV mutates rapidly and can put on a different jacket every day, making it hard for the immune system to recognize and attack it," said Stranford. "But HIV can't change all of its most basic structures. If we can find out how certain cells in some individuals attack these basic structures of HIV, we may be able to develop a vaccine to target the virus, regardless of the cloak it is wearing."

Stranford's research and its potential applications to HIV infection will provide opportunities for student learning. Inside the CD8+ cells she examines, Stranford wouldn't be surprised to find many years of undergraduate research projects in the form of hundreds of DNA chains, each one requiring study for its specific sequence, timing of production, secretion patterns, and ultimate function in the immune response against the virus. To support those student opportunities, Stranford has secured both College support and a National Institutes of Health grant to fund her research and has established a cell and molecular biology laboratory where she is already hard at work. "I'm loving the overlap between my teaching and research interests and the obvious enthusiasm of the students," she said. "I feel really lucky to be here at MHC."

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Copyright © 2001 Mount Holyoke College. This page created by Office of Communications and maintained by Don St. John. Last modified on November 9, 2001.

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