Nancy B. Schwartz, Ph.D.


  • Professor, Department of Pediatrics, Department of Biochemistry and Molecular Biology, Committee on Developmental Biology, Committee on Molecular Medicine/MPMM
  • Director, Joseph P. Kennedy Jr. Intellectual and Developmental Disabilities Research Center


  Ph.D.  University of Pittsburgh, 1971
  M.S.    University of Pittsburgh, 1967
  B.S.    University of Pittsburgh, 1965


The University of Chicago
AMB C519, (MC 5058)
5841 South Maryland Avenue
Chicago, Illinois 60637

Phone:  (773) 702-6426


Defects in Proteoglycan Synthesis Associated with Abnormal Skeletal and Brain Development

One area of interest focuses on how the machinery for sulfation, a common posttranslational modification of proteins, lipids and carbohydrates is organized and controlled in higher organisms. The integrated pathway for sulfate uptake, activation and utilization encompasses multiple components and multiple intracellular compartments. At the center of this process is the bifunctional PAPS synthetase which synthesizes phosphoadenosylphosulfate (PAPS) from ATP and SO42- in a two-step process. We have discovered the PAPS synthetase gene family, identified mutations in PAPS synthetase that lead to both human and animal chondrodystrophies and elucidated unique enzymatic properties, including channeling of the intermediate APS. Several questions are being addressed: 1) What features of the fused bifunctional PAPS synthetase account for the unique mechanistic properties, especially the channeling phenomena? Mutagenic analysis, biophysical and structural approaches are being employed; 2) What is the role of the multiple PAPS synthetase family members with respect to tissue- and developmental-specific expression? A multi-faceted approach is being used to quantitate each isoform, elucidate mechanisms of transcriptional regulation and determine the consequences of manipulation of isoform expression, include knockout and knockdown models; 3) Does PAPS synthetase have a broader role in the overall uptake, activation and utilization pathway? Potential advantageous interactions with membrane-bound and soluble components are being probed. These studies are aided by the availability of a mutant model system with a sulfation defect that results in altered proteoglycan production and abnormal skeletal growth and development. Overall the long-term goal is to provide a model of the temporal and topological organization of this critically important pathway, how it is regulated, and to correlate defects in the overall pathway with abnormal growth and development.

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