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  Nathaniel Heintz, Ph.D.
James and Marilyn Simons Professor; Investigator, HHMI
Laboratory of Molecular Biology
E-mail: heintz@rockefeller.edu

The cerebellum is a complex and highly stereotyped structure in which major pattern formation and functional organization occur after an animal is born. Research in Dr. Heintz’s laboratory is aimed at the identification of circuits, cells, macromolecular assemblies and individual molecules that contribute to the development, function and dysfunction of the mammalian cerebellum.

Dr. Heintz works to understand brain development and function based on investigations of molecular mechanisms that contribute to its histologic and functional complexities. His lab is interested in the isolation and analysis of specific genes that mark critical events in the central nervous system’s formation. Over the past decade, molecular genetic screens performed in the Heintz laboratory have identified of a variety of genes important for the development, function and dysfunction of the mammalian nervous system; studies of these genes have led to the discovery of novel components or pathways that are required for normal metabolic function in specific subsets of CNS progenitor cells (Blbp, 10-Fdh); proliferation of progenitor cells in the cerebellum and peripheral epithelia (Zipro1); modulation of nicotinic receptors in the brain and periphery (Lynx1 and other prototoxin genes); and function and degeneration of cerebellar Purkinje neurons (Lurcher (Grid2), nPIST, Beclin1).

Through these and other efforts, it has become increasingly apparent that the diversity of cell types present in the central nervous system, and the complexities of their function, must ultimately reflect the actions of many thousands of expressed genes whose products perform myriad, often subtle, roles. Accordingly, the Heintz laboratory has developed a suite of novel approaches based on the manipulation of bacterial artificial chromosomes (BACs) for the investigation of genes, cells and circuits in vivo and in vitro. These methods are the foundation of a large scale effort (called GENSAT) led by Dr. Heintz, together with Mary E. Hatten, and supported by the National Institute on Neurologic Disease and Stroke to provide a molecular cartography of the mammalian brain, and to identify BAC vectors for manipulation of specific, functionally coherent CNS cell populations.

The Heintz lab uses transgenic mice carrying manipulated BACs that target specific cell types as a means of understanding central nervous system expressed genes and phenotypes. This approach can allow efficient analysis of patterns of gene expression, the subcellular localization of encoded gene products and the mapping of neuronal projection patterns. The Heintz laboratory is also now engaged in the utilization of BAC vectors targeting defined CNS cell populations, and the application of a variety of novel genetic techniques, to molecularly characterize specific cell populations that contribute to the development and functional properties of the cerebral cortex and other brain structures. The laboratory is using these approaches in collaboration with Paul Greengard, as well as with collaborators at the Howard Hughes Medical Institute and Baylor College of Medicine, to study the properties of the normal mouse brain and to discover molecular and cellular mechanisms contributing to the profound neurological and cognitive problems associated with autism spectrum disorders, ataxia telangectasia and Rett syndrome.

CAREER

Dr. Heintz graduated from Williams College with a B.A. in biology in 1974. He received his Ph.D. from the State University of New York at Albany in 1979 and then worked as a postdoc at Washington University in St. Louis until 1982. He came to Rockefeller as assistant professor in 1983, was named associate professor in 1987, professor in 1992 and James and Marilyn Simons Professor in 2006.

Dr. Heintz was granted the American Cancer Society Junior Faculty Research Award in 1986. He was named a Pew Scholar in the Biomedical Sciences in 1985, received a National Institutes of Health postdoctoral fellowship in 1981 and a Damon Runyon-Walter Winchell Cancer Fund postdoctoral fellowship in 1979. He is a fellow of the American Academy of Arts and Sciences and an investigator at the Howard Hughes Medical Institute.