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Nathaniel Heintz, Ph.D.

James and Marilyn Simons Professor
Investigator, Howard Hughes Medical Institute

Cognition and behavior emerge from hundreds of different classes of cells in the mammalian brain, arranged in specific circuits that control various functions of the nervous system. Nathaniel Heintz has employed technologies developed in his laboratory to investigate the genes, circuits, cells, macromolecular assemblies, and individual molecules that contribute to neuronal function and dysfunction. Understanding the roles of distinct classes of neurons and the circuits that control complex behaviors can lead to more targeted treatments for a range of central nervous system disorders—from degenerative diseases such as Alzheimer’s and Parkinson’s, to neuropsychiatric conditions such as depression and obsessive compulsive disorder, to autism and other developmental disorders.

As a first step in identifying the mechanisms that are essential for normal brain functioning and those that go awry in disease, the Heintz laboratory invented a method to reproducibly target defined central nervous system cell types using genetics. Although many of the genes involved in neurological and psychiatric disorders are ubiquitously expressed throughout the brain, Dr. Heintz has proposed that disease-linked genes differentially impact finely tuned biochemical pathways controlling specific neurons and circuits. This premise is being explored and tested via several lines of research in his laboratory.

To focus on the elements that are most affected in a given disorder, the Heintz laboratory, in collaboration with Paul Greengard, developed the translating ribosome affinity purification (TRAP) technique. TRAP enables genetic and molecular profiling of a targeted cell type without requiring isolation of that cell type from a tissue. The TRAP method is now being used in drug discovery as well as basic science.

Work by Dr. Heintz has shed light on the enormous molecular complexity present in specific cell types of the central nervous system, and shown that the responses of closely related cells to genetic or pharmacological perturbations can vary substantially. He and his colleagues have also made key discoveries about the epigenetic regulation of gene expression in neurons.

An alumnus of Williams College, Nathaniel Heintz received a Ph.D. from the State University of New York at Albany, and then conducted postdoctoral research at Washington University, in St. Louis, before joining Rockefeller University in 1983. In addition to heading Rockefeller’s Laboratory of Molecular Biology, he is an investigator with the Howard Hughes Medical Institute. Dr. Heintz has been elected to the National Academy of Sciences, and he is a fellow of the American Association for the Advancement of Science.