By Leo Barolo
“I often tell people it’s a miracle when your child takes their first steps. It’s a remarkable event that, oddly, we don’t celebrate with an exchange of gifts, a pleasant song, or even a diet-busting slice of cake. Very early in my postdoctoral experience, my son stood up and walked. Movement suddenly became a passion that I’ve not let go of”, remembers Abbas Rizvi. “Later in my career, I saw how neurodegeneration can make the miracle of motion and memory rapidly decline. Both events have driven me to build a research program that offers insight into this fundamental circuit.”
Dr. Rizvi is an Assistant Professor in the Department of Neuroscience, and part of the 2023 Waisman Center cluster hire initiative. He received his Ph.D. from Harvard University under Erin O’Shea and later completed his postdoctoral research at Columbia University under the mentorship of Tom Maniatis and Richard Axel, where he combined experimental and computational innovation to dissect the neural circuits that help us move.
His lab focuses on gene regulatory events that facilitate the homeostatic structure and function of motor circuits.
“We seek to understand how cell population-wide patterns of neural activity inform action initiation and selection, the impact of higher-order epigenetic phenomena on motor learning, and how these regulatory patterns are corrupted during the onset and progression of neurodegenerative disease,” he explains.
Underlying much of their research is a desire to understand how cellular niches produce discrete molecular information exchange, enabling us to learn and interact with our environment. To do so, the team innovates experimental and computational methods, integrating in-vivo physiological recordings, single-cell genomics, and multi-omic spatial measurements.
We asked Dr. Rizvi a few questions about his research and trajectory:
How did you get your start as a scientist?
My first research job was changing pump oil at the Advanced Light Source at the Lawrence Berkeley National Laboratory. At the time, I was happy to simply be around scientists, all working to understand fundamental processes at the intersection of atomic, molecular, and optical physics. That [and other projects] steered me to intersect my physical interests with biology. I conducted my graduate studies in Erin O’Shea’s lab, where I applied mathematical modeling, biochemical, genetic, genomic and phenotypic analysis towards understanding nutrient homeostasis in Saccharomyces cerevisiae. After graduation, I trained with Tom Maniatis and Richard Axel at Columbia University, where I fell in love with the complexities of the central nervous system and developed a principled approach to computational modeling and experimental genomics.
What are the big-picture questions you are working on?
Epigenetics and Neural Activity
Our genome registers over two meters in length, an astounding number given that the average neuron is 10 microns in size. It has become clear, however, that the genome is not randomly distributed throughout the nucleus. Rather, it is organized in a cell type-specific manner and then re-organized to mediate physiological change. […] What are the time-ordered molecular events that facilitate dynamic changes in nuclear architecture? How does topological change offer specificity in transcriptional activation and alterations in physiological activity?
We extend upon these frameworks, developing methods permissive of multiplexed profiling of transcription factor binding and histone modifications within individual cells isolated from healthy and diseased central nervous system tissue. We integrate this approach with single-cell and spatial measurements of neuronal activity, nuclear architecture, and the transcriptome. Together, these measurements enable a functional link between physiological activity and genomic organization.
Non-Cell Autonomous Contributions to Neurodegeneration
Neurons interact with a complex network of specialized cells. There is an inextricable link between neuronal health and the physiological state of oligodendrocytes, astrocytes, and microglia. Local communities of these support cells actively facilitate neuronal signal transduction, promote circuit connectivity, and, in the case of disease, propagate pathological conditions that culminate in neurodegeneration. Because these effects manifest at the tissue level, they are best understood through multifaceted spatial interrogation of epigenetic, transcriptional, translational, and metabolic factors.
[Building on this], my group is also studying how spatially defined neighborhoods of glial cells support circuit-level function during learning and contribute to neuronal dysfunction during disease, with a specific focus on ALS. Through the development of novel multimodal and spatially resolved genomic methods, we are deciphering the epigenetic mechanisms that regulate transitions between neuroprotective and neurotoxic states.
What attracted you to UW?
My group’s research is highly interdisciplinary, and I am deeply impressed by the combination of rigor, innovation, and depth of scientific pursuit at the University of Wisconsin-Madison. I immediately connected with my soon-to-be colleagues in the Department of Neuroscience and the Waisman Center, both of which are spectacular and vibrant communities of teachers and learners.
Is there a single person or experience that most influenced your trajectory to where you are today?
My father was a gifted engineer. Throughout my childhood, we built, took apart, and questioned everything. He taught me to take risks, be ruthlessly practical and principled when solving problems, and be kind to others in the process.
Dr. Rizvi mentions that his research interests are accompanied by a drive and passion for mentoring, highlighting that every student deserves respect, intellectual freedom, and guidance. He concludes: “As scientists, we are all psychological beings trying to ascertain logical facts. Let’s face it, the world isn’t an easy place. Good mentorship helps”.