Acting Locally, Thinking Globally

New GW institute unites bright minds to advance HIV/AIDS research.

By Abby Vogel

On Aug. 29, 1981, GW’s Gary Simon diagnosed the first recognized HIV/AIDS patient in Washington, D.C. More than a quarter century later, Simon and other GW faculty members are leading the fight against this deadly virus by creating an institute that focuses on research, clinical care, and collaboration among those in the medical community.

The newly created GW HIV/AIDS Institute is a network of researchers and medical professionals using their knowledge to prompt studies and provide patient care in Washington, D.C., where the disease now affects 4 percent of the city’s residents. Nationally, nearly 1 million HIV/AIDS cases have been reported.

This renewed focus on the epidemic is part of the GW Medical Center’s strategic plan, which pinpoints HIV/AIDS as a priority in the university’s diverse and talented medical community.

“What we found was this enormous powerhouse of science and talent from basic to social science, from clinical expertise to public health,” says Alan E. Greenberg, chair of the Department of Epidemiology and Biostatics. Greenberg co-founded the institute with Simon, director of the Division of Infectious Diseases and vice chairman of the Department of Medicine. “We are convinced that the institute as a group will be stronger than each of us as individuals.”

Five institutions represent the pillars of the multidisciplinary and synergistic institute—GW’s School of Public Health and Health Services, GW’s School of Medicine and Health Sciences, GW’s Columbian College of Arts and Sciences, Children’s National Medical Center, and the D.C. Veterans Affairs Medical Center. Affiliate memberships have also been granted to faculty from Howard University, Georgetown University, and the Washington Hospital Center.

Through the institute, faculty provide clinical care for HIV/AIDS patients and their families, work with metropolitan area health departments, collaborate with international and national players in the policy arena, and conduct extensive research. “With the institute, we now have a rapidly responsive network with partnerships and relationships that will lend themselves to new granting opportunities and affiliations as well as value added for the University,” Greenberg says. “We are acting locally yet thinking globally.”

Greenberg and Simon are quick to acknowledge Sylvia Silver, professor of pathology and associate dean for health sciences, as the impetus for forming the institute and a leading force in articulating its vision. Silver is a well-funded and noted researcher in HIV/AIDS and recently extended her work to South Africa.

Professors Gary Simon, Sylvia Silver, and Alan E. Greenberg are making an effort to expand the reach of education and research projects addressing HIV/AIDS issues.

Jessica McConnell

As principal investigator in a collaborative effort to improve the monitoring of the HIV/AIDS epidemic in Washington, D.C., Greenberg, along with epidemiology and biostatistics faculty and staff members, is working with D.C.’s Department of Health on epidemiological and surveillance issues, including the District’s component of the Centers for Disease Control and Prevention-funded National HIV Behavioral Surveillance Project.

The institute has also developed a graduate certificate in HIV/AIDS studies, which, pending final approval from the University, will be offered through GW’s School of Public Health and Health Services beginning in the fall of 2007.

“The GW HIV/AIDS Institute will have an important impact city-wide,” says Lawrence D’Angelo, professor of pediatrics and division chief for Adolescent and Young Adult Medicine at Children’s National Medical Center. “D.C. has declared HIV/AIDS a priority, and the institute can provide the city with state-of-the-art research and collaboration.”

Fred Gordin, professor of medicine and chief of infectious diseases at the D.C. Veterans Affairs Medical Center, stresses that the recent creation of the GW HIV/AIDS Institute brings together a network of experts and facilities not formally linked in the past. “This is an opportunity for individuals like me at the VA to be integrated more fully with all the capabilities at GW,” he says.

A collaboration of this magnitude can positively impact the HIV/AIDS research agenda. Gordin explains, “Advances in the field have been remarkable in the last two decades. The work that will be done because of the development of the institute will not only help the field, but also help the people right here in our own community.”

Clinical Studies

Postdoctoral student Luke Dannenberg conducts a ChIP-chip experiment, which offers researchers the ability to study the entire genetic information in a cell and determine where a protein would bind on various chromosomes.

Jessica McConnell

“The test tube is the starting point, but until you make that jump to patients, you never know how well it is going to work,” says Simon, the institute’s co-chair. At the GW Medical Faculty Associates, many HIV-infected individuals seek antiretroviral agents and regimens. “We have established a clinical practice in HIV/AIDS here that is well recognized in the District and nationally,” he says.

More than 25 years after Simon diagnosed the first HIV/AIDS patient, the fight against HIV/AIDS continues throughout the District and the world. “The District of Columbia has a major problem in both the diagnosis and treatment of HIV-infected individuals,” Simon says. “The city is working to improve this, but it is going to take a lot of work.”

A new approach was initiated by the MFA this year: a partnership with Jeremy Brown, associate professor of emergency medicine, to establish “Opt-Out Testing,” offering HIV tests for all emergency room patients. “This is a new initiative from the Centers for Disease Control and Prevention to make sure that we identify and subsequently treat as many infected individuals as possible,” Simon says. “We believe that up to one-third of HIV-infected people don’t know they are infected and thus may not be receiving therapy. Since they are contagious, they may unknowingly be infecting others.”

Examining High-Risk Behaviors

Understanding the motivations behind risky behaviors that lead to contraction of HIV/AIDS is the stock in trade of a research team led by the psychology department’s Senior Research Scientist Carol A. Reisen and Professors of Psychology Maria Cecilia Zea and Paul Poppen, chair of the department, in GW’s Columbian College of Arts and Sciences.

In order to send the most efficient HIV prevention message, GW’s Maria Cecilia Zea, Paul Poppen, and Carol A. Reisen are trying to understand the reasons behind risky behaviors.

Jessica McConnell

“We’re interested in prevention,” Zea explains. “We are trying to understand the ‘whys’—the root causes and reasons why people behave in risky ways.” Zea adds that the underlying goal of the team’s research is determining how to send the most effective message about HIV prevention to the Latino community.

“We’ve learned that it’s really complex,” Zea says about why the incidence of the disease has not continued to decline. “It’s not as straightforward as receiving information and changing behavior. There are a number of variables contributing to risk—poverty, discrimination, geography.”

Poppen says the team’s research has dispelled an important myth about behavior—that risky behavior is based on individual personality differences. He explains, “What we’ve seen is almost anyone may engage in some form of risky behavior depending upon the context of the particular sexual event itself—if you’ve had alcohol or drugs, who your partner is, what the setting is, and so on. What we’re studying is how the context associated with specific episodes may make it more likely for anyone to engage in risky behavior.

“The bigger point,” he adds, “is that information is not enough. That’s part of the problem with health issues that are behaviorally related. Behavior is not that easy to control. It’s a big challenge.”

Adolescents and Young Adults

Cases of HIV infection continue to rise in adolescents and young adults 12 to 24 years old, according to CDC officials. Yet challenges in reaching HIV-infected youth still hamper clinical research.

“When working with HIV-infected adolescents, adherence to therapy takes on a completely new meaning, especially in light of the fact that many of our patients are literally managing their own health and well being,” D’Angelo explains.

Shown above are reagents used in a ChIP-chip experiment including vials of transcription factors and various protein coding genes from HIV-1 genome.

Jessica McConnell

With the support of the National Institutes of Health and the CDC, Children’s National Medical Center currently is participating in two major research programs. The Pediatric AIDS Clinical Trials Group led by Hans Spiegel, assistant professor of pediatrics, microbiology and tropical medicine, involves 26 sites in the United States and abroad and evaluates pharmacokinetics, short-term safety, tolerability, and antiviral activity of HIV medication in patients 6 to 17 years old.

D’Angelo leads the Adolescent Trials Network with 15 sites examining the care, prevention, and treatment aspects of HIV in adolescents. The long-term goal of the program is to develop viable community-based HIV prevention interventions.

Additionally, D’Angelo explores ways to limit secondary transmission in HIV-infected adolescents. Identifying HIV-infected adolescents presents its own set of challenges, as many of these individuals are not aware of their HIV status. Children’s National Medical Center has taken a lead role as a community resource, offering counseling and testing services to adolescents and young adults.

Forum Facilitates HIV Research Debate

The Forum for Collaborative HIV Research is an independent public-private partnership established in 1997 to facilitate discussion on emerging issues in HIV research. Housed in GW’s School of Public Health and Health Services’ Department of Prevention and Community Health, the forum brings together experts from government, industry, academia, the patient community, and foundations to address HIV prevention, treatment strategy, health services, and policy.

Forum Executive Director Veronica Miller says the membership profile ensures independence and neutrality, and is the key to the forum’s uniqueness. “The forum identifies barriers that keep the field of HIV research from moving forward faster. At the same time, it builds communication and collaboration between these various groups.”

The forum has benefited from the participation of a wide range of GW researchers, including Zea; Greenberg; John Palen, School of Public Health and Health Policy associate dean and associate professor of health services; and Jeffrey Levi, associate research professor of health policy.

Graduate student Mala Ghai and Professor Fatah Kashanchi view the result of an experiment that looks at the proteome of an infected cell using 2-Dimensional gel electrophoresis before a Mass Spec Proteomics analysis.

Zea participated in a forum workshop that examined racial and ethnic minority issues in the management of HIV care, prevention, and research. She explored whether Latino gay men disclose that they are HIV-positive to their social network.

Greenberg participated in a workshop to study biomedical interventions to HIV infection. Instead of the traditional approach to educating people about how their sexual behavior can lead to HIV infection, this workshop investigated methods such as using topical compounds called microbicides to protect against sexually transmitted infections, providing antiretroviral treatments to people at high risk to HIV exposure, circumcising men, and treating herpes simplex virus type 2 (HSV2) since HSV2-positive men showed a consistent two-fold increase in the risk of HIV acquisition.

Additional forum projects range from assessing the current state of HIV therapeutic vaccine development and potential barriers for moving vaccines forward, especially through the regulatory process, to designing clinical trials of treatments and interventions for lipodystrophy—body fat redistribution that causes side effects that may threaten the long-term success of antiretroviral therapy.

Systems Approach to Studying HIV/AIDS

Fatah Kashanchi’s research explores the entire HIV infection system, including the virus, the cells it infects, and the methods involved in the infection and replication processes. Through the use of bioinformatics—the collection, classification, storage, and analysis of biological information using computers—Kashanchi, professor of biochemistry and molecular biology, deciphered the complex code of HIV-1, the virus that causes AIDS. Kashanchi’s research continues to rely on bioinformatics to study HIV using two technologies: genomics and proteomics.

“I want to know how certain proteins and pathways involved in HIV infection talk to each other,” Kashanchi says. “The only way to study this is to use the systems biology approach of both proteomics and genomics.”

To study the genomics of HIV-infected cells, or all of the nucleotide sequences in the chromosomes, Kashanchi routinely searches through tens of thousands of gene arrays for alterations in pathways, including transcription, translation, and cell death. Using this information as well as various bioinformatics tools, he recently designed inhibitor drugs that seek and destroy HIV-infected cells.

Reagents used to perform molecular biology experiments related to HIV-1 genomics and proteomics research.

Jessica McConnell

To study the proteomics of HIV-infected cells—the structure, function, and interactions of the proteins produced by the genes—Kashanchi inspects amino acid chains for changes to viral proteins following infection with HIV. This approach could ultimately lead to an AIDS vaccine.

“Genomics and proteomics allow us to study the effects of specific inhibitors and peptides that could be used as drugs against HIV,” Kashanchi says.

To learn how the human immune system responds to HIV, Kashanchi recently developed the first small animal model for HIV/AIDS that utilizes human stem cells to repopulate the animal with human immune cells. With this model, he will trace the steps of an HIV virus as it enters and infects an immune cell. With this route mapped out, Kashanchi can test different peptides and drugs to see if they inhibit entry of HIV into an immune cell.

HIV Infection and Increased Risk of Heart Attack

HIV infection is often associated with an increased risk of developing atherosclerosis—a build up of fatty deposits in the vessels feeding the heart. Deposits slowly narrow the coronary arteries, and complete blockage leads to heart attacks. Researchers previously attributed these increased risks in HIV patients to antiretroviral therapy. However, new research conducted by Michael Bukrinsky, professor and vice chair of the Department of Microbiology and Tropical Medicine, and graduate students Zahedi Mujawar and Matthew Morrow shows that this increased risk may be due to HIV infection itself, a side effect of HIV’s strategy to increase its infectivity.

“HIV prevents infected cells from releasing cholesterol into the plasma,” Bukrinsky says. “This makes the virus happy, because it needs cholesterol to make new virus particles capable of infecting other cells.”

Bukrinsky currently is investigating what happens when HIV-infected cells are treated with drugs that stimulate cholesterol release from cells. “The cells still make the virus, but the virus is practically noninfectious, because it cannot get necessary cholesterol,” he says.

In another avenue of research, Bukrinsky examines small molecule compounds called oxadiazols that inhibit HIV. These novel antiviral agents come at the perfect time—when incidences of drug toxicity and resistance are increasing during long-term treatment of HIV-infected patients. Because HIV can replicate in non-dividing cells, blocking cell division is not enough to stop HIV infectivity. Instead, HIV must be blocked from entering the cell nucleus. The oxadiazols Bukrinsky discovered inhibit viral DNA from entering the nucleus and can be used in addition to the HIV cocktail, a three-drug combination regimen, to boost its effectiveness.

“We participated in the design and testing of these compounds,” Bukrinsky says. “Currently, studies are focusing on the pharmacokinetics of these compounds to improve their delivery. We hope that clinical trials will be initiated soon.”

For more information about the GW HIV/AIDS Institute, visit

Abby Vogel is a research writer in the Medical Center Communications and Marketing Office.

Linda Dent, Sarah Freeman, Debbie Goldstein, and Thomas Kohout contributed to this article.

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© 2007The George Washington University
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