Destined to be a Doctor, but in Love with the Lab

On her way to fulfilling a childhood dream of becoming a physician, Lisa Armitige made an interesting discovery. Several discoveries, actually, but perhaps the most unexpected was that her desire to be a doctor led her to an added vocation.

“I came here to be a physician, but I found a second love in the laboratory,” said Armitige, M.D., Ph.D.

By the time she became the 50th graduate of the joint M.D./Ph.D. program of The University of Texas Health Science Center at Houston and The University of Texas M.D. Anderson Cancer Center this past summer, Armitige had spent 12 years tenaciously cultivating her interests as both clinician and scientist through school and residency.

Last month, Armitige was granted a faculty appointment at UT-Houston as an assistant professor in the internal medicine department, general medicine division, and continues her fast-paced life with additional research in the genetics of Mycobacterium tuberculosis with scientists in the department of pathology and laboratory medicine.

That dedication to both research and clinical practice is exactly what the M.D./Ph.D. program aims to inspire among its graduates.

“There’s an opportunity today to conduct great translational research that takes laboratory research out of the lab and applies it in a patient-care setting. It’s important that M.D./Ph.D. programs emphasize that. They are uniquely positioned to pull that off,” said program director Dianna Milewicz, M.D., Ph.D., Doris Duke Distinguished Clinical Scientist, and professor and vice chairman of internal medicine. “Many M.D./Ph.D. programs produce scientists only. Ours is geared to produce clinicians who are also scientists.”

She praised Armitige’s success in the lab and commitment to caring for patients.

“I hope that’s what Lisa does for the rest of her career. We should never lose sight of what the patient looks like, just so we remember why we do the science in the first place,” Milewicz said.

It’s hard to imagine Armitige turning off that path.

“I decided when I was 6 years old that I wanted to be a doctor. My mother is a nurse, but she never pressed me to choose a particular career. She simply instilled a good work ethic in me and encouraged whatever I felt was my calling,” she said.

Armitige said there was no specific event or person that triggered her desire to be a physician.

“It’s been more like a calling,” she said.

After her first year of medical school, Armitige took a summer job in the laboratory of Audrey Wanger, Ph.D., an associate professor in the department of pathology and laboratory medicine with a research interest in tuberculosis. Her work involved epidemiological research on TB cases at Lyndon B. Johnson Hospital, mainly lab analysis of strains of the TB bacterium. Armitige was fascinated by the world’s deadliest infectious disease, which was coming back to the United States after having been virtually eradicated here.

“I talked with Audrey about the Ph.D. degree and she encouraged me to pursue it,” Armitige said.

She later met with Peter Davies, M.D., Ph.D., professor of integrative medicine and pharmacology, and then director of the M.D./Ph.D. Program, and applied to the UT-Houston Graduate School of Biomedical Sciences during her second year of medical school.

Armitige did four of six clinical rotations during her third year of medical school and worked in Wanger’s lab 20 hours a week.

“I left two rotations to return to OB/GYN and psychology. Then I dropped full time into the lab,” she said.

Armitige said it was a bit of a shock to go from being a third-year medical student to starting anew in the lab. But during the first year she did a rotation with Heidi Kaplan, associate professor of molecular genetics and microbiology, and discovered an interest in genetics, which led to a summer course at Cold Spring Harbor Laboratory in New York.

“I came back from Cold Spring Harbor all excited. Researchers were saying that the molecular genetics of TB couldn’t be altered, but I believed it could. I set out to prove it. I got my doctoral committee together and they approved my TB project but also advised me to get a backup plan,” Armitige said.

She chose a difficult area of research, explained Steve Norris, Ph.D., professor of pathology and laboratory medicine and a member of Armitige’s doctoral committee.

“There were only a couple of labs in the world at the time that had successfully generated mutations in Mycobacterium tuberculosis,” Norris said. “Lisa is a good example of perseverance paying off.”

Her work focused on genes that coded for fibronectin-binding proteins – proteins that help the microbe stick to human tissue. What would happen if these genes were knocked out of the organism? With great effort, Armitige knocked out two of the three genes.

“We found out that they were only the third and fourth genes ever knocked out of the TB bacterium,” she said.

Knocking out one of the genes had no effect on the microbe – the mutant strain of TB still swiftly infected the lungs and spread to other organs in lab mice. But the other knockout had an effect, at first appearing to spare the mice entirely.

“We initially thought we had a vaccine,” Armitige said. “But as the mice aged and their immune systems weakened, TB eventually flared, albeit in a more diffuse form in the lungs.”

The mutation in Armitige’s strain of TB might one day be combined with others to fashion a vaccine, Norris said.

She will continue the vaccine research under a grant led by Chinnaswamy Jagannath, Ph.D., an associate professor of pathology.

As her research advanced, Armitige worked half a day a week for three years in the Thomas Street Clinic for HIV/AIDS patients with Roberto Arduino, M.D., associate professor of infectious diseases. She followed the progress of the same patients for years.

“As a medical student, you do one-month rotations and you don’t see what happens to people after that month is over. I had an opportunity none of the other students had.”

Her work at Thomas Street smoothed her transition to the clinic in 1997 and 1998 when she returned to finish medical school. From there it was on to a residency at Memorial Hermann Hospital in medicine and pediatrics. As busy as Armitige was, she kept at her doctoral program, working in the lab several days a week throughout her residency.

Now, with residency complete, the emphasis will shift back to the lab and research on TB genetics under projects led by Robert Hunter, M.D., Ph.D., professor and chairman of pathology and laboratory medicine, and Jagannath. She expects to spend about 75 percent of her time in research early in her career, while working in medicine and pediatric clinics the rest of the time.

“You get spoiled here in the Texas Medical Center. I have worked at St. Luke’s, LBJ, Memorial Hermann, M.D. Anderson, and out in the clinics. I wouldn’t trade my training here for anything,” Armitige said.

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©2006 Texas Medical Center

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