Connecting Biology & Behavior

Connecting Biology & Behavior

Meharry’s Dr. James Hildreth aims to use new research center to find effective  strategies for reaching out to african-americans at risk for hiv/aids

Dr. James E.K. Hildreth

Title: Director, Comprehensive Center for Health Disparities Research in HIV, Meharry Medical College

Education: Bachelor’s, Harvard University; Ph.D.,  University of Oxford, Oxford, England, M.D., Johns Hopkins University School of Medicine

Previous position: Professor of Pathology, Pharmacology and Molecular Sciences and Director, Monoclonal Antibody Core, Center for AIDS Research, Johns Hopkins University School of Medicine, 2002-2005

NASHVILLE, Tenn.
Bright morning sun floods through the wall of windows in Dr. James E.K. Hildreth’s new fourth-floor office at Meharry Medical College. Light bathes his corner sitting area, washes over the framed photographs of family on his desk and spotlights the half-unpacked boxes scattered along one wall, hinting at his cherished collection of African art and books.

Hildreth, a prominent HIV/AIDS researcher, and director of Meharry’s new Comprehensive Center for Health Disparities Research in HIV, has just been on the job since July, and he is already feeling a sense of accomplishment. He’s getting windows in his laboratory and the painted “accent walls” that he went to battle for. For Hildreth, it’s not just about aesthetics. It’s about productivity and function.

When you are on the brink of a breakthrough, poised to usher in the fruits of years of biomedical research that could stop the spread of the deadly virus that causes AIDS, lights, windows and a bit of color aren’t a lot to ask for.

“Clearly, infrastructure at Meharry isn’t what it is at Hopkins,” admits Hildreth. When he came to the college, he found “walls painted battleship gray, and every other light bulb missing.” Changing that atmosphere was near the top of Hildreth’s list.

Meharry did, however, have the most important tool it needed: the BioSafety Level 3 lab and air filtration system necessary for handling live HIV. And Hildreth, a professor of internal medicine at the college, is already making plans for an 18,000-square-foot lab accommodating eight to 10 HIV/AIDS investigators at Meharry’s old hospital. 

“Our presence will enhance an existing and stellar research infrastructure,” he says.

Hildreth, 48, may be the man that everyone has their eye on, but he is quick to point out that he’s not a one-man band. Says Hildreth, “It’s amazing what you can accomplish when it doesn’t matter who gets the credit.”

He points to the role of investigators like Dr. Bindong Liu of China, Dr. Waldemar Popik of Poland and Dr. Donald Alcendor, all colleagues at Johns Hopkins who share his passion for finding a cure for AIDS. All three have since joined him at Meharry, a fact that amazes Hildreth.
“My work and my time at Hopkins were well respected even more so than I thought,” Hildreth says. “When other researchers heard that I was coming here, they wanted to follow me.”

One of those who followed was Popik.

“He was my competitor,” says Popik of Hildreth. Both scientists were investigating lipid transfer and HIV infection while at Hopkins.

“I had done all that I could do at Hopkins. And when I found out that James was establishing a lab in Nashville, I asked if I could join him. He said yes, and I accepted immediately,” adds Popik, who relocated to Tennessee with his wife. “I decided to come because of [Hildreth’s] great science and his personality; a combination that you’d like your boss to be. There are others here who came from Hopkins and we feel like a family, not competitors. Now we can join our forces and really do something good.”

Inside a scientific breakthrough
In 1987, HIV/AIDS was mysterious and and frightening to doctors and researchers who peered through their microscopes at the virus or into the faces of the dying. At the time, Hildreth, a newly hired pharmacologist at Hopkins, “was told to work on AIDS.” Hildreth had little interest in the disease, but he did want to know “how is the HIV virus able to steal cells?” He eventually found his research niche, but the answer to his question would not come for 13 years.

“I decided to work on AIDS on my own terms using adhesion molecules and retroviruses,” says Hildreth, a Rhodes Scholar.

Hildreth’s research is based on the discovery that “cholesterol is active in HIV’s ability to penetrate cells and that removing fatty materials from a cell’s membrane can block infection,” he says. In 2000, Hildreth and his team discovered that without the fatty materials, or lipids, the virus that causes AIDS could not enter cells, and ultimately could not infect and spread throughout the human body.

The next year, Hildreth and his team began exploring cyclodextrin, a natural compound that binds to cholesterol and is often used commercially to flavor beverages and make medicines soluble. By using the compound to drain cholesterol from HIV, the team managed to develop a cyclodextrin-based gel capable of disabling HIV and blocking its transmission through sex. That year, Hildreth and his investigators did just that. Their work was published in the journal AIDS Research and Human Retroviruses in 2003.

According to Hildreth, his discovery differs from other significant HIV findings because it focuses on a component of the virus that is actually made by cells, rather than proteins encoded within the virus. Hildreth’s breakthrough research resulted in the development of a minimally toxic vaginal cream that acts like a “chemical condom,” blocking the transmission of the virus. So far, he says, the vaginal cream has been tested in the lab with great promise on animals infected with HIV. The next step, Hildreth says, is securing FDA approval to use the chemical condom in clinical trials. He holds six U.S. patents, including one that will give him control over the use of cyclodextrin as an HIV-blocker.
“If we are able to pull this off,” says Hildreth, “it would be a very fantastic thing.”

And what if he were the one to someday find a cure for AIDS?
“I don’t even have the wildest dream of being that person. It’s just that such a thing is too fantastic to think about,” Hildreth says. “But through some stroke of fortune, if I were, I would work really hard to ensure that drug compound or treatment is made available to the vast majority of people who need it. I just hope that whenever a cure is found, that sentiment would be the same.”

What People Want to Know
Hildreth is getting used to answering two questions from those who know his reputation and the institution he left. “They’re asking can I do what I do at Meharry?” Hildreth says. “Or ‘Why did you leave Johns Hopkins, a globally-recognized research university, and the prestige and research dollars that come with being a tenured professor at such an institution?’”

For Hildreth, it was time to move on. “It was about personal growth,” he says. “I had done everything that I wanted to do at Hopkins. I decided that being at Meharry over the long term, that I could have the greatest impact.”

After all, few in the HIV/AIDS research community had their eye on Meharry before he arrived, but Hildreth and Meharry President John E. Maupin Jr. hope to change all that.

“We had $9 million of research annually in 1994. Now, we’re at $26 million,” Maupin said in a recent interview with The Tennessean. Five years from now, Maupin says he wants research dollars to be closer to $40 million.

It represents a dramatic return to form for Meharry. The college’s reputation, once stellar among African-American institutions, has suffered over time. The 130-year-old medical school was on the brink of closing in the early 1990s. Like many other historically Black institutions, Meharry was floundering under the weight of enormous deficits and the threat of losing its accreditation. The college hit possibly its lowest point in 1994, when Meharry lost its residency programs in obstetrics (surgery) and pediatrics. That was also the year Maupin became president of the institution.

By 2001, Maupin and his administration were well on the way to resuscitating the ailing college. Meharry was operating in the black and student board scores were the highest in the school’s history (see Black Issues In Higher Education, July 19, 2001).

This June, Meharry ended a seven-year capital campaign, surpassing its $125 million fund-raising goal. Alumni contributed $13.5 million of the campaign’s $127.5 million in gifts and commitments. And the college, which has had its accreditation status restored for the last several years, has more than doubled the percentage of students passing their national board exams on the first try.

But some problems remain. Just one month before Hildreth came on board, the medical college was censured, or formally condemned, by the American Association of University Professors, a college professor’s advocacy group. AAUP said in a report that Meharry mistreated faculty and that the administration didn’t share its power.

Maupin, however, is undeterred and considers recruiting Hildreth as an important first step in launching Meharry’s new HIV research center.
“The addition of a world-class researcher like Dr. Hildreth to our team is a huge step toward achieving our goal of establishing one of the country’s leading research centers in HIV/AIDS,” Maupin says.

“He wanted to come to Meharry as much as we wanted him to come here,” says Jill Scoggins, the college’s spokeswoman. “When the funding was awarded to us to create the center, it was just a perfect match of what we were looking for and what he wants to do personally and professionally,” Scoggins says of Hildreth.

Hildreth says he’s happy to be at Meharry, an institution with a storied tradition of producing many of the nation’s Black doctors, dentists and scientists since 1876.

“For me, coming to Meharry is a bit of a dream come true,” he says. “I’m looking forward to exciting things to come.”

With a research emphasis on eliminating health disparities, Meharry is focusing its efforts in three major areas — cancer, HIV/AIDS and women’s health. The new Health Disparities Center Hildreth oversees was launched with $17 million from NIH. Next year, the college is scheduled to open the Center for Women’s Health Research, which will become the nation’s first such facility devoted solely to research on women of color.

Dr. Valerie Montgomery Rice, chairwoman of Meharry’s Department of Obstetrics and Gynecology, will head the 10,000-square-foot center when it opens next year. Approximately $7.5 million in startup money and construction funds came from NIH, the National Center for Research Resources and the National Center on Minority Health and Health Disparities, says Rice.

She is one of the people most responsible for bringing Hildreth to Meharry. Rice chaired the search committee for the new HIV center’s director. She says Hildreth’s name kept cropping up whenever the call went out for candidates. Rice decided to pick up the phone and reach out to him after hearing a rumor that he was planning a move to a pharmaceutical company. Her passionate pitch included describing Meharry as an institution that nurtured families and a place where he could have “an impact.”

“I didn’t know him at the time, but when I called, I boldly said, ‘I heard that you are going to a pharmaceutical, but there is an opportunity  here at Meharry that you need to explore,’” Rice recalls.
“We hit it off immediately,” she says. Within two weeks of that recruitment call, Hildreth was on the campus for a visit.

And she’s already talking about him changing the course of history with his microbicide. “If he made the discovery at Hopkins, it would be perceived that it was because he was at Hopkins. If he makes the discovery at Meharry, the partnerships and collaboration will be more evident and our stature will be elevated,” she says. “For physicians of color, those are important things.”

Tackling HIV and Staying Connected
The windows in Hildreth’s office not only let in the light, he says they keep him connected to the people, the places and the legacy and despair that offer a glimpse of Black life in Nashville. He worries about getting his lab and the HIV Center up and running fast enough, because people are dying. And he worries about the need to train the next generation of scientists and physicians who will be poised to tackle HIV and the specter of pathogens that he predicts “will emerge more deadly than AIDS.” 

There are already a number of grassroots and community-outreach organizations targeting African-Americans with HIV/AIDS education and prevention messages, “but there are things that [the center] can do,” Hildreth insists.

One of them is reaching out to the Black church, which he says “is a critical part of the solution,” but Hildreth knows that he could be in for some resistance. Although African-Americans make up only 13 percent of the U.S. population, they account for 57 percent of new HIV infections. Still, the epidemic is one that many Black churches have chosen to ignore.

A self-described Christian, Hildreth says he is determined to find a way to help clergy and religious leaders “overcome cultural barriers and thinking that says sex is taboo.” Taking to the pulpits of Nashville churches is among his plans.

Hildreth knows that helping halt the spread of HIV/AIDS in Nashville won’t be easy, but he thinks that the health disparities center can make a difference if researchers ask the right questions. One of those questions is why do so many African-Americans put themselves at risk for contracting the deadly virus?

“Once the right questions are asked and the answers are there, there needs to be intervention and ones that are meaningful and culturally sensitive,” says Hildreth who believes that “issues of personal responsibility and behavior are paramount to better understanding and addressing the spread of the disease among our people.”

He is developing an integrated model that blends biology, community outreach and behavior science to explore and address the cultural, environmental and social variables that contribute to the high infections rates in Blacks.

“You can’t separate biology from behavior, which accounts disproportionately for why so many African-Americans are infected with HIV/AIDS,” says Hildreth. He is looking to the behavioral scientists on his team to help the Center build credibility in the community and find effective strategies for reaching those at risk. “Failing to not do something to change behaviors,” he says, “is not an option.”



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