July 9, 2024
The seventh leading cause of death in the United States, Alzheimer’s disease (AD) is a clear and urgent national health and research priority. For millions of Americans, including MIT graduate student Mingus Rae Zoller, it’s also a deeply personal one. With a new Gilliam fellowship funded by the Howard Hughes Medical Institute, Zoller will have support to advance understanding of the neurodegenerative disease that has unexpectedly afflicted her father.
The Zoller family has no history of AD and her father, a physicist, had the typically protective effects of a lifetime of education and intellectual activity on his side. But as with most cases of Alzheimer’s disease, there is no clear cause, genetic or otherwise, to point to.
“This is the biggest mystery of my life. How did my Dad get AD?” Zoller said. “If I can contribute one tiny bit of information to explain how AD progresses or how someone could get it, that would be personally fulfilling. That’s a big driving force for me.”
The Gilliam fellowship also taps into other deep sources of motivation for Zoller. It provides her and her adviser Li-Huei Tsai, Picower Professor in The Picower Institute for Learning and Memory, with a number of resources to promote diversity, equity and inclusion in the sciences. That intersects both with Zoller’s enthusiasm for promoting their value in science and her awareness of the particularly difficult challenges that neurodegenerative disease can pose among already disadvantaged populations, such as finding adequate healthcare when money is tight.
“My commitment to equity and inclusion in science is deeply personal, fueled by my experiences as a neurodivergent Black woman and witnessing the impact of neurodegenerative diseases on marginalized communities,” she said. “Diversity is not just a moral imperative; it’s essential for scientific excellence, as diverse teams are generally found to be more innovative and effective at solving complex problems.”
Working to address Alzheimer’s
Currently in her second year of graduate study in MIT’s Department of Brain and Cognitive Sciences, Zoller has homed in on research questions in Tsai’s lab that are indeed bringing innovation to bear on the disease’s considerable complexity.
Since 2016 the Tsai lab has led a series of studies showing that increasing the power and synchrony of 40Hz gamma frequency neural activity can reduce Alzheimer’s pathology and symptoms in mice and safely produces encouraging effects in human volunteers. The lab’s investigations in mice of how those surprising results might come about have yielded findings that boosting 40Hz neural rhythms has specific and important effects both on the brain’s immune cells, or microglia, and other cell types including astrocytes, which facilitate the brain’s blood circulation and waste clearance. The lab’s most recent findings showed that 40Hz stimulation (or “GENUS” for Gamma Entrainment Using Sensory stimuli) prompts specific neurons to release peptide signals that, in turn, prompt astrocytes and the brain’s glymphatic system to increase how much it flushes out the toxic, AD-associated protein amyloid beta.
The lab has also recently shown how AD-associated mutation of the protein TREM2 undermines the healthy function of microglia.
Zoller will tackle a set of questions raised by these new results and the lab’s previous findings about how 40Hz stimulation also changes the activity and gene expression of resident immune cells. There are intriguing intersections, for instance, that the findings may have with recent discoveries of immune cell populations called “border macrophages” that live in the meninges that surround the brain.
“So the main question I’m interested in is, is there a connection between neuronal activity and brain border macrophages that could contribute to AD pathology,” Zoller said. “How can we therapeutically target border macrophages, whether it’s through GENUS or some other way? I feel like there’s a lot of untapped potential.”
One of Zoller’s current sets of experiments, for instance, looks at whether 40Hz stimulation helps address problems associated with TREM2 mutation in microglia. Notably, the protein is also highly expressed in border macrophages.
Working to help others
Zoller, who studied neuroscience as undergraduate at Reed College, said she is enjoying her work in the Tsai lab and at MIT in general. Her colleagues across the lab and department are collaborative and study such a wide variety of neuroscience topics, that there is always something new to learn, for instance at seminars. Zoller said she has found the nurturing environment of the Tsai lab to be inspiring as she works to help others.
Indeed, Zoller said, she is finding many opportunities to act on her passion for promoting equity and inclusion in science.
“Taking part in the Brain and Cognitive Sciences Application Assistance Program and the Women+ of Color Project, enabled me to assist dozens of scientists from underserved backgrounds in honing their academic writing skills and crafting compelling statements of purpose for their graduate applications,” Zoller said. “I am also a Diversity Ambassador for my graduate program and the DEIJ representative for my lab. I plan to expand my mentorship efforts through MIT programs aimed at supporting under-served minorities such as the research scholars post-bac program and LEAH Knox Scholars Program.”
Zoller said she’d also like to form a club at MIT to support students who have loved ones with neurodegenerative disease and financial challenges that could hinder their care. A goal would be to engage policymakers to find ways to address those gaps.
She won’t be alone in doing her work. Not only will she be working with Tsai in her research and via the Gilliam fellowships programs, but also the fellowship affords opportunities to interact with other Gilliam Fellows.
“Being part of the Gilliam community is an incredible honor,” Zoller said. “It offers an unprecedented opportunity to forge lifelong connections with individuals who share similar backgrounds and aspirations and is an incredibly supportive network that will be invaluable throughout my personal and professional journey.”
