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A Legacy of Discovery

By Steve Goldstein | Photography by Michael Leong

Some are born scientists, some have science thrust upon them and, in the case of Michael I. Bukrinsky, M.D., Ph.D., some have a family history that conveys a certain inevitability to their life’s work. Fortunately for the George Washington University School of Medicine and Health Sciences (SMHS), where Bukrinsky serves as professor and interim chair of the Department of Microbiology, Immunology, and Tropical Medicine, his family was also instrumental in ensuring that his groundbreaking work in HIV biology and drug design was done in the United States and not in his native Russia.

Michael Bukrinsky
Michael I. Bukrinsky, M.D., Ph.D., professor and interim chair of the Department of Microbiology, Immunology, and Tropical Medicine

With a research focus on HIV biology and inflammatory diseases, Bukrinsky and his team have been studying cardiovascular disease in HIV-infected patients. In addition to his leadership role in the department, Bukrinsky is one of the senior researchers leading GW’s Washington, D.C. Developmental Center for AIDS Research (D.C. D-CFAR), which is charged with providing scientific leadership and institutional infrastructure to promote HIV/AIDS research and to develop the next generation of investigators.

Yet all of this might never have been.

Science is literally in Bukrinsky’s DNA. His father, Ilya Shapiro, was a prominent biologist and his mother a virologist. When they weren’t working at their labs, his parents poured over difficult-to-obtain scientific journals, which were in short supply in the Cold War-era Communist Soviet Union. “I saw them reading all the time and they seemed happy and excited,” recalled Bukrinsky, “so by age 10 or 11, I had decided that I was going to be a scientist, too.” His parents sent him to Moscow School No. 2, the top mathematics school in the city, whose director would later be persecuted by the Soviet authorities for allowing too much free speech. Later, Bukrinsky would attend Moscow Medical School and earn his Ph.D. at the prestigious Institute of Molecular Biology.

Meanwhile, in 1978, Shapiro defected to the West to escape the Soviet Union’s restrictive working conditions for scientists. With his father branded a traitor, young Michael took his mother’s maiden name — Bukrinsky. (Augmenting his scientific pedigree, Bukrinsky’s mother later married Viktor Zhdanov, a famous Russian virologist and Deputy Minister of Health in the USSR, who led the effort to eradicate the smallpox virus.) By the mid-1980s, Bukrinsky began to relate to his father’s frustration. “I rose to ‘interim junior researcher,’ ” he said with a laugh. “It was a joke; I had no real position.” The final straw came when Soviet authorities rejected an invitation for Bukrinsky to visit Cuba to address the nation’s growing HIV problem.

In 1989, the last year Jewish people were allowed to emigrate from the Soviet Union, Bukrinsky received an official invitation to leave, thanks to his father’s friend in Israel. Ultimately, Bukrinsky went to the United States; his mother would follow three years later, after the dissolution of the USSR. “I left because I wasn’t allowed to move to any position where I could do something in research,” he explained.

Shapiro was also instrumental in matching his son with leading HIV researcher Mario Stevenson, Ph.D., at the University of Nebraska in Omaha. It was a good fit: Bukrinsky stayed for three years and the lab published numerous papers in top journals. “This was the time my future interests were formed,” said Bukrinsky. Then fate took another turn when he met Anthony Cerami, Ph.D., who was head of a research institute at North Shore University Hospital on Long Island, N.Y.

“We had decided to expand the scope of our research to include HIV and, after calling people in the field, we identified a young investigator named Michael Bukrinsky,” said Cerami, a distinguished researcher who pioneered the hemoglobin A1c test used by diabetics worldwide and founded the Warren Institute, a not-for-profit that conducts biomedical research. “I worked with Michael on several aspects of HIV and enjoyed every moment. He is without a doubt one of the leaders in the field today,” said Cerami.

The two became close friends and when Bukrinsky expressed a desire to find a new position, Cerami endorsed GW, which was actively expanding its Department of Microbiology, Immunology, and Tropical Medicine. In 2001, Bukrinsky arrived on campus and, in a short time, according to his peers, managed to rise to the top of a highly competitive HIV/AIDS field. He’s also become an admired mentor, training doctoral students who have gone on to some of the best laboratories in the world. One of them, Sergey Iordanskiy, Ph.D., was a postdoc from 2001 through 2007 and now continues to collaborate with Bukrinsky as a member of the research faculty at GW. “Michael is a fantastic mentor and scientific adviser who allows us to work almost independently. He always considers the opinions of young scientists and guides them in the right direction when problems arise,” said Iordanskiy.

Bukrinsky’s lab has focused on, among other projects, analyzing cholesterol metabolism in HIV-infected cells to understand why people with HIV are at increased risk of arteriosclerosis. As anti-retroviral drug regimens have allowed HIV patients to live longer, a clinical problem has arisen because they are developing arteriosclerosis at an earlier age than the general population. At first, Bukrinsky said, experts thought that the increased risk was related to the drugs, but that theory was proved false. “In fact, tests showed that when taken off drugs, the risk actually went up — not down,” said Bukrinsky. “That’s when we came in with our project.”

Bukrinsky’s team discovered that the HIV virus has a specific effect on cholesterol metabolism by inhibiting a critical cholesterol transporting mechanism. Specifically, the HIV virus suppresses cholesterol efflux, which is critical for maturation of the high-density lipoprotein (HDL) particles, the key atheroprotective factor in blood. The HDL particles perform two functions: anti-inflammation and prevention of plaque formation in the arteries. But HIV patients have low levels of HDL, explains Bukrinsky.

Once the role of HDL in arteriosclerosis was discovered, pharmaceutical companies went to work on drugs that stimulate the transportation of cholesterol. Bukrinsky’s team capitalized on these developments, finding that the same drugs also inhibit viral replication. “This suggests that these drugs will be of dual benefit to the patients — they will not only fight arteriosclerosis but they’ll also inhibit replication of the HIV virus. This is really very exciting,” Bukrinsky said.

Alan Remaley, M.D., Ph.D., a well-known HIV expert at the National Institutes of Health, said Bukrinsky’s work on the role of cholesterol and lipid metabolism in AIDS “holds great promise” regarding the effect of some HIV drugs on lipid and lipoprotein metabolism. He also praised Bukrinsky’s finding that the replication of HIV itself is in-part dependent upon cholesterol metabolism. The viral effect on cholesterol metabolism and trafficking has been observed in other viruses, suggesting that it can be used as a target for therapeutic approaches against HIV as well as other viruses. “This creates the opportunity to perhaps control the replication of HIV,” said Remaley. As a result of these observations, Bukrinsky is cited as an author on more than 10 U.S. patents.

With 2011 marking the 30th anniversary of the battle against HIV/AIDS, Bukrinsky’s work comes amid other breakthroughs such as the discovery that an HIV-infected individual can reduce the risk of sexual transmission by beginning anti-retroviral drug treatment sooner. Other successful interventions have helped prevent HIV-infected mothers from transmitting the virus to their children during birth. All are steps toward what the Obama administration calls an “AIDS-free generation.”

“A vaccine will be the ultimate solution for the epidemic, but I don’t think this would solve all the problems,” said Bukrinsky. “To me, the real solution would be to cure the disease, to make people who have it free of the virus.” To this end, Bukrinsky’s research has focused on the use of therapeutic, not preventative, vaccinations. His lab is working to better understand latently infected cells, which remain in the body throughout a patient’s life and may become active when drug therapy is stopped.

In addition to his administrative responsibilities as acting chair, there is Bukrinsky’s work with the D.C. D-CFAR, where he directs two of the five “cores” that provide support for HIV-related research in Washington. He is in charge of the developmental and basic science cores; the other three include administrative, clinical and behavioral science, and prevention and biostatistics. He has noted a shortage of HIV/ AIDS researchers doing basic science work and said, “this is an area we need to develop in order to support the other research studies [and] the only way to accomplish that is to attract new people, especially young investigators.”

For Bukrinsky, that “next generation” begins at home. His youngest daughter is in high school, his oldest daughter is a lawyer in Virginia, and his son just started medical school in Grenada. Not surprisingly, his wife, Tatiana Pushkarsky, is a research scientist in his department at SMHS.

Thinking back to those nights watching his parents read scientific journals at home, Bukrinsky sees the same sense of excitement and discovery in the young researchers he’s mentored. He doesn’t regret his decision to “escape,” as he has put it. “If I had stayed in Russia, I’d still be a scientist, but I wouldn’t be able to do what I’ve achieved here,” he said. “I know I did the right thing.”

For more information about Michael Bukrinsky, M.D., Ph.D., visit www.gwumc.edu/bukrinsky.