Heads of Laboratories
James and Marilyn Simons Professor; Investigator, HHMI
Laboratory of Molecular Biology
heintz@rockefeller.edu
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 brain.
Dr. Heintz works to understand brain development and function based on investigations of molecular mechanisms that contribute to its histological and functional complexities. His lab is interested in the isolation and analysis of specific genes that play critical roles in the central nervous system (CNS). Over the past decade, molecular genetic screens performed in the Heintz laboratory have identified 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 and 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 neuronal activity 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 CNS, and the complexities of their functions, must ultimately reflect the actions of many thousands of expressed genes whose products perform myriad, often subtle, roles. Accordingly, the Heintz lab 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 and supported by the National Institute of Neurological Disorders 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 CNS expressed genes and phenotypes. This approach can allow efficient analysis of patterns of gene expression, subcellular localization of encoded gene products and mapping of neuronal projection patterns. The Heintz lab 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. This work led to the recent publication of a new method — Translating Ribosome Affinity Purification (TRAP) — that can capture the translational profile for any type of cell in any tissue in any organ. The laboratory is using these approaches in collaboration with Rockefeller’s 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 that contribute to the profound neurological and cognitive problems associated with autism spectrum disorders, ataxia telangiectasia and Rett syndrome. In addition, the TRAP method has applications for research into afflictions as varied as cancer metastases, coronary artery disease, Parkinson’s disease, Alzheimer’s disease and diabetes.
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, 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 and 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.
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