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   Ph.D. University of Illinois, Urbana, 1970
Postdoctoral Training: Harvard University, 1970-1972; Massachusetts Institute of Technology, 1972-1974
 Carlos Hirschberg 

Research description

The Role of Novel Regulation of Posttranslational Modifications in Development and Disease

Our laboratory is interested in studying the biogenesis, structure and function of lower and higher eukaryotes' cell surfaces and the extracellular matrix by using a combined biochemical, molecular biological and genetic approach. Our particular effort is focused on glycoproteins, glycolipids, and glycosaminoglycans. These play important roles in the regulation of cell growth, intercellular recognition, cell adhesion, and as receptors for hormones, toxins and growth factors.

A major research effort has centered around mechanisms of glycosylation, sulfation and phosphorylation of the above-named compounds. Specific questions which are being asked include the intracellular membrane topography of glycosylation, sulfation and phosphorylation reactions and how precursors are transported from their intracellular site of synthesis to the site(s) of glycosylation, sulfation and phosphorylation. We have characterized a number of transporters in the membrane of the rough endoplasmic reticulum and Golgi apparatus which transport precursors into the lumen of these organelles. These transporters are antiporters. We and others have described Chinese hamster ovary cells, yeast, protozoa, nematodes, insects and plants which are defective in transport of sugar nucleotides into the Golgi apparatus lumen. These mutants have a developmentally impaired phenotype and can cause a virulent wild type organism to become avirulent, demonstrating that the transporters are of physiologic relevance and may become drug targets. Recently the first diseases in such transporters were described: leukocyte adhesion deficiency II syndrome in humans and complex vertebral malformation in bovines. We have purified and cloned some of these transporters by using biochemical and molecular biological approaches, including genetic complementation. More recently, we are also studying the function of these transporters in C. elegans and are cloning and disrupting the genes of enzymes involved in the above posttranslational modifications, i.e., a Golgi GDPase from K. lactis, Candida albicans,
and C. elegans. This approach should enable us to determine the functions of specific glycoproteins and glycosaminoglycans during development.


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