Breakthrough Tuberculosis Research Is Inspired by Real Patients

Dr. Stephen Carpenter has always been interested in learning about the pathogenesis of disease, or how a disease develops. While in his first year of clinical medicine residency at NYU Langone Health, he gained the opportunity to do research on tuberculosis (TB). As a member of the house-staff at NYU’s Bellevue Hospital, Dr. Carpenter also had the unique opportunity to work in the TB ward, which allowed him to have firsthand experience with patients with tuberculosis and then study tuberculosis immune response in the lab. “That combination really piqued my interest in taking problems that we observe clinically and trying to figure out a way in the lab to get answers,” Dr. Carpenter said.

After his residency, Dr. Carpenter began an infectious disease fellowship at Harvard Medical School and found a researcher who was also interested in the immune response to tuberculosis, Dr. Sam Behar. Together, they worked for the next six years on a variety of studies while Dr. Carpenter received his PhD. “It really set the tone for my career, and I knew I wanted to be focused on immune responses to tuberculosis,” he said.

Answering Questions About Tuberculosis

During his work with Dr. Behar, Dr. Carpenter noticed an odd phenomenon that kept occurring in the tuberculosis mouse model studies. He couldn’t understand why, once infected, it took almost two weeks before they would see T cells that target TB in the infected mice. “We realized that no matter what we tried, there was a delay in transporting the bacteria to the lymph nodes, which is where T cells get primed,” he said. “That led me to wonder, why is it that the memory T cells from vaccination cannot interact with the infected macrophage in the lung?”

With that in mind, Dr. Carpenter started his own lab where he sought to answer those questions but focused specifically on human cells. This meant getting samples from individuals infected with TB to study their immune response. His current study builds on that idea, with the hope of identifying CD4T cells that can recognize macrophages infected with virulent Mycobacterium tuberculosis (the bacterium that causes TB).

“Perhaps when individuals are first infected with TB, they generate a very different and diverse T cell response, as opposed to later,” he said. By conducting research with a clinical cohort in Uganda, he hopes to understand the early T cell response in the lung and which T cells that persist later after infection. In this study, his team collects samples from people who live in the same household as someone with active tuberculosis. These subjects test negative for TB at the time of enrollment but are retested every three months for up to a year to determine if and why they begin to test positive. Many of them will turn positive in the first 3-6 months, so it allows the research team to study the immune system, before and during the infection.

This is done with a simple blood draw, but when some participants become newly TB positive, they also agree to undergo a bronchoscopy so that the researchers can isolate immune cells from the lungs. “We think we are going to identify antigens that these T cells target very early that are going to be important for vaccine development,” Dr. Carpenter explained. “For example, if T cells target certain antigens, we have the opportunity to amplify a T cell response that targets them and perhaps prevent infection from taking hold."

Only a year into the study, Dr. Carpenter plans to continue the study as long as possible to help determine and study long-term effects of TB. “Research in general takes time and effort to make meaningful findings, it's not something that happens quickly. So, you have to find an area of research that you love enough that you are willing to work long and hard because persistence is key, and eventually you will get results.”

Learn more about tuberculosis research and other researchers that the Lung Association supports through grants by visiting: Lung.org/research.