Hannah Stadtler completes her Ph.D. with a mission to understand HIV and the brain

By Christopher Richmond

Hannah Stadtler knew whom she wanted to work with before even arriving at VCU.

Without having set foot on campus, she had cold-emailed Gretchen Neigh, Ph.D., a professor in the Virginia Commonwealth University School of Medicine's Department of Neuroscience and Anatomy. Neigh's work at the intersection of stress and biology aligned exactly with where Stadtler wanted to take her science.

"I kind of targeted her before I came to VCU" in 2020, Stadtler said. "I knew about her research and knew that I wanted to work in an HIV space."

That instinct paid off. In late February this year, Stadtler defended her dissertation, completing the Ph.D. portion of her M.D.-Ph.D. in the School of Medicine's Medical Scientist Training Program. She did so as part of the inaugural cohort of the Wright Center's Translational Biomedical Sciences (TBS) T32 Training Program, an early milestone for the center's newest predoctoral training grant.

The Wright Center for Clinical and Translational Research accelerates science that promotes healthy communities, and Stadtler's dissertation tackled a pressing but underexplored problem: Women living with HIV face a disproportionate burden of cognitive impairment compared with men with HIV and women without it.

Examining a cellular link

As HIV has become a manageable chronic condition, comorbidities like memory loss and cognitive decline have grown more urgent. Stadtler's work focused on the role that mitochondria, the "power plants" of human cells, may play in that picture.

"I think mitochondria are the key to everything," she said.

Working with blood samples from women with HIV, collected through a collaboration with Johns Hopkins researcher Leah Rubin, Ph.D., Stadtler measured mitochondrial health alongside detailed cognitive assessments and clinical histories. Two findings stood out.

• Women who had experienced childhood trauma showed significantly elevated baseline cellular respiration, suggesting their mitochondria were under greater stress.
• And women with higher "proton leak" - a measure of inefficiency in the cellular machinery that produces energy - were more likely to struggle with learning and memory.

The research was recently published in the journal AIDS.

"This was the first step of establishing whether this relationship exists," Stadtler said, adding that there are now many more avenues to explore.

Ongoing animal studies are investigating whether blood-based mitochondrial markers could predict what's happening in the brain, a potential step toward interventions that could improve cognitive outcomes for patients.

The road to VCU and beyond

Stadtler grew up in Spotsylvania, about an hour north of Richmond, and attended Davidson College in North Carolina, where a scholarship program introduced her to research. She always planned to go to medical school, but as graduation approached, she found herself dreading the end of her time in the lab.

"I was so sad that I was going to stop researching," she said. "And then I went down the rabbit hole of Ph.D. programs and how research and science really come from each other and should complement each other."

Two years at a research institute at Duke University followed, where her laboratory work on hookah smoke and lung cells ran alongside clinical experiences with people living with HIV. The combination pointed her toward translational research - and eventually to VCU, the Clinical and Translational Sciences Ph.D. program and Neigh's lab.

The relationship with Neigh has been central to everything that followed.

"I am nothing without mentorship - I am no stranger to a cold email," Stadtler said. "And that's one of the beautiful things about both Dr. Neigh and VCU and the Wright Center itself: Everybody has been very supportive and willing to connect people."

She called Neigh, who is also the center's director of education and mentoring, a "collaborative queen" - quick to acknowledge the edges of her own expertise and connect her trainees with someone who can fill the gap.

Partway through her Ph.D. in the long-standing Wright Center graduate program, Stadtler was selected for the center's new T32 predoctoral training grant, and she ended up becoming one of the first scholars supported by the NIH-funded program.

The fellowship deepened her training in community-based research, and it connected her with a community mentor: Allie Farley, a registered dietitian with VCU's Ryan White Program, who was launching a 12-week community nutrition course for people living with HIV in Richmond. Stadtler helped build a data framework to evaluate the program's effectiveness.

With her dissertation behind her, Stadtler is now transitioning back to the clinical side of her M.D.-Ph.D., with about two years of medical school remaining. Her goal is a career that keeps science and medicine in constant dialogue - ideally split evenly between research and patient care.

"That's the beauty of translational research - because that's always the goal: to better people's lives, and to really use science to answer some of these really critical questions," Stadtler said. "The two are so intertwined, and I feel medicine is nothing without research. And I think great research comes from gaps in medicine."

The Wright Center's T32 Translational Biomedical Sciences training program is funded by the National Center for Advancing Translational Sciences, grant T32TR004362. For more information, visit cctr.vcu.edu.

The project described was in part supported by CTSA award No. UM1TR004360 from the NCATS. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the NCATS or the National Institutes of Health.