Severe Mental Illness: From Genes to Mechanisms to Therapeutics

This two-day in-person symposium on September 16 and 17, 2025, will be chaired by Dr. Steve Hyman, director of the Program in Brain Health at Broad Institute, Dr. Kris Dickson of the Stanley Center at Broad Institute, Dr. Zhanyan Fu of the Stanley Center at Broad Institute, Dr. Evan Macosko of the Stanley Center at the Broad Institute and Harvard Medical School, and Dr. Elise Robinson of Massachusetts General Hospital and associate director of Human Genetics at the Stanley Center. It will bring together scientists working on the frontiers of genetics, neurobiology, computational psychiatry, and therapeutic development for schizophrenia, bipolar disorder, and related neuropsychiatric disorders.

The central theme of this symposium revolves around addressing the challenges of turning human genetics findings for severe mental illnesses into biology that will inform and drive the identification of biomarkers and novel therapeutics. In this symposium, speakers will present important new findings that will have an impact on neuropsychiatric research. The program will include keynote speeches from David Altshuler, EVP and CSO of Vertex and Belinda Lennox, Head of the Department of Psychiatry, University of Oxford along with a wide range of other talks, panels, and a poster session.

Agenda

Chairs: Kris Dickson, Zhanyan Fu, Steve Hyman, Evan Macosko, Elise Robinson

Day 1: Tuesday, September 16, 2025

8:00 - 8:45 am Breakfast
Opening Session
8:45 - 8:55 am Welcome Steve Hyman Harvard University & Broad Institute
Keynote 1
8:55 - 9:05 am Keynote Introduction Steve Hyman Harvard University & Broad Institute
9:05 - 10:05 am Keynote: Humanizing drug discovery David Altshuler Vertex
Session 1: Psychiatric genetics and genomics: Progress and challenges Chair: Elise Robinson
10:05 - 10:10 am Session Introduction Elise Robinson MGH & Broad Institute
10:10 - 10:40 am Gene discovery for severe mental illnesses Ben Neale MGH & Broad Institute
10:40 - 11:55 am Coffee Break
10:55 - 11:25 am Functional convergence of common and rare variant risk for neuropsychiatric disease Elise Robinson MGH & Broad Institute
11:25 - 11:55 am Psychiatric genetics through the lens of neurodevelopmental transcriptomics Michael Gandal University of Pennsylvania
11:55 - 12:25 pm The biology of adversity Jason Buenrostro Harvard University & Broad Institute
12:25 - 1:25 pm Lunch
Session 2: Molecular and neural mechanisms of neuropsychiatric disorders - driving biomarker and therapeutic discovery Chair: Zhanyan Fu
1:25 - 1:30 pm Session Introduction Zhanyan Fu Broad Institute
1:30 - 2:00 pm Probing and rescuing dysfunctional brain circuits in depression Conor Liston Cornell University
2:00 - 2:30 pm Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor Jonathan Weissman MIT & Whitehead Institute
2:30 - 3:00 pm CRISPR-mediated bipolar disorder-associated gene deletion in sleep-regulating mouse neurons Julie Kauer Stanford
3:00 - 3:15 pm Coffee Break
3:15 - 3:40 pm Poster Session previews
3:40 - 4:50 pm Panel discussion on genetic medicine – addressing quantitative gene defects Moderator: Evan Macosko HMS & Broad Institute Toby Ferguson Voyager Kelsey Martin SFARI Jonathan Weissman MIT & Whitehead Institute Morgan Sheng MIT & Broad Institute
4:50 - 5:00 pm Closing Remarks Evan Macosko HMS & Broad Institute
Stanley Center Poster Session
5:00 - 7:00 pm Reception and poster session McGovern Institute Atrium

Day 2: Wednesday, September 17, 2025

8:00 - 8:45 am Breakfast
Keynote 2
8:45 - 8:55 am Keynote Introduction Steve Hyman Harvard University & Broad Institute
8:55 - 9:55 am Keynote: Autoimmune psychosis – hope or hype? Belinda Lennox University of Oxford
Session 3: Understanding mental illness mechanisms using human model systems and clinical cohorts Chair: Evan Macosko
9:55 - 10:00 am Session Introduction Evan Macosko HMS & Broad Institute
10:00 - 10:30 am Characterizing the clinical impact of genetic variants in psychotic disorders using decades of longitudinal healthcare data Olli Pietiläinen University of Helsinki & Broad Institute
10:30 - 11:00 am Developmental dysconnectivity in a genetic risk model for psychosis Carrie Bearden UCLA
11:00 - 11:20 am Coffee Break
11:20 - 12:00 pm Fireside Chat: Humanizing mental illness: the power of stories Lisa Genova with Steve Hyman and Eliza T. Williamson
12:00 - 1:00 pm Lunch
Session 4: Frontiers of mechanistic and therapeutic discovery in the central nervous system Chair: Randy Buckner
1:00 - 1:05 pm Session Introduction Randy Buckner Harvard University
1:05 - 1:35 pm Decoding cell-type-specific mechanisms in the human brain to guide therapeutic discovery Panos Roussos Icahn School of Medicine
1:35 - 2:05 pm Animal models of schizophrenia and bipolar disorder based on human genetics Morgan Sheng MIT & Broad Institute
2:05 - 2:25 pm Coffee Break
2:25 - 3:15 pm Panel discussion – What do we need to get industry re-engaged? Moderator: Steve Hyman Harvard University & Broad Institute James Cronican Boehringer Ingelheim Fiona Elwood Johnson & Johnson Steve Paul Seaport Therapeutics
3:15 - 3:30 pm Closing Remarks Steve Hyman Harvard University & Broad Institute Steve Paul Seaport Therapeutics