Yale School of Medicine has received a nearly $25 million grant from the Aligning Research to Impact Autism initiative to develop foundational maps and models of the developing human brain and investigate how and when autism-related differences emerge. The grant is part of ARIA’s Human Developmental Neurobiology Research Hub.
The research is co-led by Nenad Sestan of Yale School of Medicine and Paola Arlotta of Harvard University and focuses on early brain development.
Researchers intend to combine experimental biology, imaging, computation and clinical collaborations to produce developmental reference models that could support biomarker discovery and research into earlier or more precise interventions.
One component of the program will create a high-resolution connectome model of the developing human brain spanning prenatal development through adolescence.
Working with Hao Huang of the University of Pennsylvania, Sestan’s laboratory plans to map how long-range connections, local cellular circuits and synapses emerge and mature over time.
A second research pillar will map cell types and gene regulatory programs across brain regions and developmental periods, combining single-cell multi-omics and spatial data to establish a baseline for typical development and examine autism-associated divergence.
Arlotta’s laboratory will use patient-derived brain organoids to investigate relationships among genetics, developmental timing, cellular development, synapse formation and network activity.
A fourth component, led by Marinka Zitnik of Harvard Medical School, will develop generative multimodal AI models operating at cellular resolution.
Those models will integrate data across genes, proteins, pathways, cells, brain regions, circuits and patient phenotypes in an effort to identify biomarkers, prioritize potential therapeutic targets and simulate possible interventions. The longer-term objective is a “virtual cell” platform capable of modeling how timing and dosage could influence developmental outcomes.
The new award follows a separate $27.7 million ARIA grant to Yale School of Medicine in July 2025 supporting research led by Murat Günel.
KEY QUOTES:
“We are very grateful to ARIA for their investment in Yale. Their philanthropy is advancing a new era of autism research, which we hope will lead to an understanding of its earliest beginning in the developing brain. The impact of their grant will extend well beyond Yale School of Medicine, creating knowledge that can guide earlier detection, clearer biomarkers, and more precise interventions for individuals with autism and their families.”
Nancy J. Brown, MD, Jean and David W. Wallace Dean of Yale School of Medicine
“My colleagues and I are profoundly grateful for ARIA’s visionary support. This award enables us to advance our research into the development of the human brain’s neural circuits. By bringing together experts across disciplines and institutions, we aim to better understand how brain development unfolds and how autism emerges. Ultimately, we hope this work accelerates discovery, improves early detection, and informs more effective interventions.”
Nenad Sestan, MD, PhD, Harvey and Kate Cushing Professor of Neuroscience at Yale School of Medicine
“This additional grant from ARIA will support YSM researchers and collaborators at other institutions in generating shared datasets, experimental models, and AI-enabled tools aimed at speeding biomarker discovery and the identification of novel therapeutic targets. It will help build an integrated, developmental understanding of autism, opening new paths for earlier, more personalized approaches.”
Nancy J. Brown, MD, Jean and David W. Wallace Dean of Yale School of Medicine
