David Jacobowitz, Ph.D.,
Professor of Anatomy, Physiology and Genetics

Laboratory of Clinical Sciences; National Institute of Mental Health
Ohio State University School of Medicine 1963
 
Parasagital Section of the 17/18 Mouse Embryo Brain Research Interests:
Dr. Jacobowitz received a masters degree from the Department of Anatomy and a Ph.D. from the Department of Pharmacology at the Ohio State University School of Medicine in 1963. He did his postdoctoral fellowship at the University of Pennsylvania under Dr. George Koelle, who developed the histochemical stain for acetylcholinesterase. He subsequently stayed at the University of Pennsylvania for nine years, achieving the rank of associate professor before moving to the National Institute of Mental Health, where he has remained for the last twenty-nine years. At NIMH, he established the Section on Histopharmacology, a unique laboratory dedicated to the belief that the challenge of uncovering the secrets to brain function lies in the unraveling of neuronal conductivity. To that end, a portion of his work has been involved in mapping of neuronal systems of the brain. His guiding principle is that knowledge of the building blocks, or "nuts and bolts," give us clues about both how the nervous systems operate and how they might fail to disease and injury.
 
Dr. Jacobowitz's laboratory has produced complete maps of 11 neuronal systems -- more than have come out of any other laboratory in the world: catecholamine/acetylcholinesterase, alpha-melanocyte stimulating hormone, corticotropin releasing hormone, calcitonin gene-related peptide, galanin, atrial antriuretic factor, growth hormone releasing hormone, bovine pancreatic polypeptide, motilin, melanin-concentrating hormone, and the maps of peptide receptor binding sites (CRF, CFRP, and galanin angiotensin II). As a major repository of information concerning sites of localization for potent brain neurochemicals, the lab has given birth to a field of neuroscience that Dr. Jacobowitz describes as "brain cartography."
 
Dr. Jacobowitz was also involved in the biochemical mapping of the discrete localization of neurochemicals within the brain using the brain micropunch technique. His lab assayed a variety of neurochemicals by several methods, such as the radiomicroenzymatic procedure for neurotransmitters/enzymes and radioimmunoassays for peptides that were available at the time. These neurochemical maps were very useful adjuncts to the histochemical maps already published. Important findings evolved from this technology, which uses stereotaxic lesions in the brain to determine sites of localization of neuronal pathways.
 
- In the early 1980s, Dr. Jacobowitz undertook a new initiative to uncover important tissue markers that could be used to identify neuronal or glial subpopulations. He realized that two-dimensional gel electrophoresis, a comparatively new procedure, could be a useful method for revealing interesting proteins presumably contained in subpopulations of neuronal systems. His long-term goals were to isolate and purify those proteins and to generate antibodies that could localize proteins within subsystems of the brain and periphery. This would essentially lead to functional studies utilizing biochemical and immunocytochemical procedures. Using two-dimensional gel electrophoresis, his lab constructed an atlas showing the location (on polyacrylamide gels) and relative concentration of about 100 proteins in twenty-five distinct neuroanatomical regions of the brain. This atlas was the first attempt at systematically classifying the mass, charge and relative concentration of proteins present in a variety of regions of the rat brain. Dr. Jacobowitz is currently searching for interesting proteins that appear in human brain tumors. Two-dimensional gel electrophoresis coupled with mass spectroscopy reveals the identification or amino-acid sequence of the proteins of interest.
 
The long-term goal of isolation, purification, and antibody production of proteins in the brain began to be realized in 1988, when the group identified a calcium binding protein. After working for 10 years, they isolated and purified a protein from the guinea pig brain that was initially called "protein 10" and is now known as "calretinin." Calretinin was recently found in mesothelioma, a deadly lung cancer. Dr. Jacobowitz's laboratory also generated a rabbit antiserum to this protein that was mostly neuron-specific. They have found a point mutation in the calretinin cDNA, which is a major subject of current work in the laboratory.
 
- Dr. Jacobowitz has recently produced a state-of-the-art color atlas entitled, "Chemoarchitectonic Atlas of the Developing Mouse Brain," which is invaluable to all workers interested in the fetal brain. He is currently engaged in cell-culture work on neuronal cells isolated from the brain of the rat embryo.
 
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4301 Jones Bridge Road
Bethesda, Maryland 20814

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