Mark Fishman, M.D.
Massachusetts General Hospital
Our goal is to understand the genetic and neuronal structure of social behavior in vertebrates.
We use the zebrafish because we have found previously, based on our large-scale genetic screen, that this species provides access to key genetic nodes, entrance points to complex biological processes. For example, complemented by physiological analyses, we were able to begin to understand the fashioning of vertebrate organ systems and the onset of their function.
Social behavior is key to evolution, and its failure the major impediment evident in many psychiatric disorders. The time is ripe for its investigation because of the availability of computational and genetic tools. With quantitative and automated video tracking and imaging, and algorithms which train computers to recognize specific activities, we can capture and analyze robust social behaviors, such as courtship, shoaling, aggression, and leadership.
We utilize the transparency of the larval zebrafish to relate such behaviors to the activity of single cells in the brain. We then compare the behaviors and circuitry of fish with defined genetic changes, introduced by CRISPR-based genetic modification of specific loci, including those putatively related to human disease.
(Because the infrastructure required for this work was set up at the Novartis Institutes for BioMedical research (NIBR), the majority of the experiments are conducted there. NIBR is at 181 Mass Ave, next to MIT.)
Mark Fishman is Professor in the Harvard Department of Stem Cell and Regenerative Biology and Chief of the Pathways Clinical Service service at the MGH for patients with complex medical disorders. His current research focus is on the genes that guide social behavior, using genetics of the zebrafish.
In the 1990s, by harnessing the first large-scale genetic screens in zebrafish (performed in collaboration with W. Driever and contemporaneously with C. Nuesslein-Volhard), and by providing much of the early genomic infrastructure, Fishman’s lab helped to make the zebrafish a cornerstone of developmental biology, and led to revelation of many of the pathways that guide vertebrate organ development, particularly the heart and vessels.
From 2002-2016 Fishman was the founding President of the Novartis Institutes for BioMedical Research (NIBR). During his tenure, NIBR discovered and brought through successful clinical trials 90 new medicines in more than 120 indications. He brought a particular focus on regenerative medicines as treatments for disorders of aging.
Fishman graduated from Yale College and Harvard Medical School and trained in medicine and Cardiology at the MGH. Prior to his time at NIBR, he was the Founding Director of the Cardiovascular Research Center and Chief of Cardiology at the Massachusetts General Hospital. Fishman sits on the Executive Committee and Council of the National Academy of Medicine, and is a Fellow of the American Academy of Arts and Sciences.
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