Mark C. Fishman, M.D.
Using larval zebrafish, our goals are: (1) to understand the genetic, neuronal, and molecular basis of social behavior, and (2) to unravel the heart-brain axis, using the larval zebrafish to define the circuitry and function of autonomic control of cardiac function.
1. Social behavior. 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 have captured and analyzed robust social behaviors, such as courtship, shoaling, aggression, and leadership, and discovered the precursors to such complex functions even in the larval fish. This makes this emergent behavior accessible to single cell and circuit analysis of neuronal activity.
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.We 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.
2. Cardiac nervous system. The heart and brain are intimately linked, with second-by-second neural feedback to cardiac physiology from internal baro- and chemoreceptors. In addition, the heart has its own intrinsic set of nerves, today of poorly understood function. We are exploring the development and precise cell fate and connectivity of intrinsic neurons of the heart, and those that connect heart and brain, in order to understand how homeostatic control develops.
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.
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 has served on the Executive Committee and Council of the National Academy of Medicine, and is a Fellow of the American Academy of Arts and Sciences.
Genetic control of collective behavior: Research reveals how genes related to psychiatric conditions can influence group behavior in zebrafish
Survival of the zebrafish: mate, or flee? Study reveals zebrafish make an unexpected decision when faced with conflicting opportunities
For new medicines, turn to pioneers: Most transformative medicines originate in curiosity-driven science, evidence says