
Daniel Geschwind, M.D., Ph.D.
Bio
Daniel Geschwind, M.D., Ph.D. seeks to identify the genetic causes of neurologic and psychiatric disorders including autism and neurodegenerative dementia. His research program integrates basic neurobiology, genetics and genomics to develop a systematic understanding of these conditions. The ultimate goal of Geschwind's work is to develop new therapies for neurologic and psychiatric disorders for which no treatments are currently available.
The Geschwind lab creates disease models ranging from genetically engineered mice to stem cell-based mini brain organoids to study the development of neurologic and psychiatric disorders. Mini brain organoids are three-dimensional tissues grown from stem cells that mimic human brain growth, structure and development, making them vital to the study of complex neurological diseases. These models provide scientists with an unprecedented perspective on the biological and genetic underpinnings of brain growth, development and disease processes. Geschwind uses systems biology – computational and mathematical modeling of complex biological systems – to study the networks of gene expression in these disease models. This approach enables him to analyze large amounts of data and identify common genetic patterns that are correlated with normal brain functions, such as repair after injury, and hallmarks of disorder, such as autism-related language delay.
His research group found that the brains of patients with autism, schizophrenia and bipolar disorder have some common patterns–and key differences—of gene expression. Identifying the genetic patterns associated with these diseases is the first step to discovering new drugs to reverse them. Geschwind's lab also developed the first map of gene regulation in human cortical neurogenesis, the process by which neural stem cells turn into brain cells and the cerebral cortex expands. The cerebral cortex is the part of the brain that is responsible for thinking, perceiving and sophisticated communication. Their research identified factors that govern brain growth, and in some cases, set the stage for psychiatric disorders that appear after infancy, such as schizophrenia and attention deficit hyperactivity disorder (ADHD).
Despite advances in stem cell-based brain models, age-related neurologic disorders – including Alzheimer's disease and Parkinson's – remain difficult to study in living tissue. This is because growing and maintaining mature human brain cells in the lab is quite difficult. Geschwind and his collaborators are working to overcome this hurdle by using mathematical predictions to identify factors that drive neuronal maturation in the human brain but that are absent in neurons grown from stem cells in the lab. They will use these factors to mimic the effects of aging in neurons created in the lab so that researchers can more accurately model age-related brain diseases in the lab and identify new therapies.
Geschwind earned medical degree and a doctorate degree in neurobiology from the Yale University School of Medicine. He completed his post-doctoral fellowship, internship and residency at the UCLA David Geffen School of Medicine. He was elected to the National Academy of Medicine in 2011.
Publications
- Broad transcriptomic dysregulation occurs across the cerebral cortex in ASDPublished in Nature on Wednesday, November 2, 2022
- Leveraging genomic diversity for discovery in an electronic health record linked biobank: the UCLA ATLAS Community Health InitiativePublished in Genome Medicine on Friday, September 9, 2022
- Functional regulatory variants implicate distinct transcriptional networks in dementiaPublished in Science on Friday, August 19, 2022
- Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytesPublished in Nature Communications on Friday, June 25, 2021
- Pre-existing conditions in Hispanics/Latinxs that are COVID-19 risk factorsPublished in iScience on Friday, March 19, 2021
- Long-term maturation of human cortical organoids matches key early postnatal transitionsPublished in Nature Neuroscience on Monday, February 22, 2021
- The dynamic landscape of open chromatin during human cortical neurogenesisPublished in Cell on Thursday, January 11, 2018
- Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus InfectionPublished in Cell Reports on Tuesday, October 10, 2017
- Chromosome conformation elucidates regulatory relationships in developing human brainPublished in Nature on Wednesday, October 19, 2016
- Advancing the understanding of autism disease mechanisms through geneticsPublished in Nature Medicine on Wednesday, April 6, 2016
- A Quantitative Framework to Evaluate Modeling of Cortical Development by Neural Stem CellsPublished in Neuron on Wednesday, July 2, 2014
- Identification of Differentially Expressed Proteins in Murine Embryonic and Postnatal Cortical Neural ProgenitorsPublished in PLOS ONE on Tuesday, February 9, 2010
Honors & Affiliations
Honors
- Raymond Adams Award, American Neurological Association 2016
- NARSAD Distinguished Investigator, Brain & Behavior Research Foundation, 2015
- Elected member, American Association of Physicians, 2014,
- Wiersma (Endowed) Visiting Professor, California Institute of Technology, 2012
- Elected member, National Academy of Medicine, 2011
- Scientific Service Award, Autism Speaks, 2008
- KAVLI Distinguished Visiting Professor, University of California, San Diego, 2007
- Derek Denny-Brown Neurological Scholar Award, American Neurological Association, 2004
Affiliations
- Director, UCLA Center for Autism Research and Treatment
- Co-Director, UCLA Center for Neurobehavioral Genetics
- Associate Director, Precision Health, UCLA Clinical and Translational Science Institute
- Member, UCLA Bioinformatics Graduate Programs in Bioscience Home Area
- Member, UCLA Brain Research Institute
- Member, UCLA Genetics & Genomics Graduate Programs in Bioscience Home Area
- Member, UCLA Neuroscience Graduate Programs in Bioscience Home Area
- Member, Society for Neuroscience
- Co-Head of Faculty, Genomics and Genetics, Faculty of 1,000
- Deputy Editor, Biological Psychiatry
- Editorial board, Neuron, Cell, Current Opinion in Genetics and Development, Neurogenetics, Human Molecular Genetics
- Board of Reviewing Editors, Science
Funding
Geschwind's research is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Mental Health, the National Center for Advancing Translational Sciences, the National Institute on Aging, the Adelson Medical Research Foundation, the Tau Consortium, the Paul G. Allen Family Foundation and the Simons Foundation.