Special Lecture by Mauro Costa-Mattioli

Abstract: Life depends on the capacity of cells to withstand stress, repair damage, and maintain functional balance —homeostasis. In the brain, when that balance erodes, the consequences are far-reaching: it is the common biological foundation of most chronic diseases, and its progressive deterioration underlies aging itself. Yet the field has largely studied these conditions in isolation: one gene, one pathway, one disease at a time.

Here, I argue for a disease-agnostic alternative, asking the more fundamental question of what sustains homeostasis and resilience in the first place. I will present some of the most recent work from my lab demonstrating that when the homeostatic machinery is chronically dysregulated, through specific genetic variants, aging, or neurodegeneration; cognitive resilience and brain function collapse. Crucially, this state is not fixed. Single molecular interventions can act as a homeostasis-resetter, reawakening the brain's intrinsic capacity to adapt and restoring brain function across neurological conditions. Finally, I will propose a new discovery engine aimed at targeting resilience itself, rather than chasing disease-specific mechanisms, as the foundation for the next generation of brain medicines.

Short-Bio: Mauro Costa-Mattioli grew up in rural Uruguay, where an early fascination with molecular biology and genetics set the course for his career. He trained across three countries, earning degrees from the University of the Republic (Uruguay), Pierre and Marie Curie University (Paris), and the University of Nantes, followed by postdoctoral work at McGill University (Canada). In 2008, he joined Baylor College of Medicine's Department of Neuroscience, where he served as Professor, Cullen Endowed Chair in Neuroscience, and Director of the Memory & Brain Research Center until 2022. He is now a founding principal investigator at Altos Labs.

His lab studies how homeostatic pathways support brain resilience and health — from molecules to cells to whole organisms, and even the microbes that share our bodies. He identified the integrated stress response (ISR) as a key driver of cognitive dysfunction across a range of memory disorders, work that has shaped how the field understands learning and memory and has spurred several companies to develop ISR-targeted therapies. More recently, his team serendipitously discovered that a specific gut microbe can influence brain function and social behavior. Several clinical trials, including one led by his group, found that treatment with this microbe eased social deficits in children with autism; evidence that brain-related conditions might sometimes be treated by targeting the gut.

Throughout his career, Costa-Mattioli has earned numerous accolades, including the Eppendorf & Science Prize in Neurobiology (2008), the Searle Scholar Award (2009), the Whitehall Scholar Award (2009), the International Society for Neurochemistry's Young Investigator Award (2013), the Michael E. DeBakey Excellence in Research Award (2013), and the UCSF Presidential Chair Award (2019). He serves on several editorial boards, including Neuron and the National Academies of Sciences, Engineering, and Medicine Life Sciences board.