Gillian Air  /  Sanjay Bidichandani  /  Robert Broyles
Paul DeAngelis  /  Jay Hanas  /  Martin Levine
Guangpu Li  /  Jialing Lin  /  Hiroyuki Matsumoto  / Blaine Mooers /  Ann Louise Olson 

Karla Rodgers  /  Robert Steinberg  /  Leon Unger  /  Paul Weigel   

Christopher West  /   Adam Zlotnick

Structure-function of Glycosaminoglycan Receptors and Hyaluronic Acid Synthases and their roles in human diseases. 

Our laboratory has a broad interest in how glycosaminoglycans like hyaluronic acid (HA) function normally in the body and how they are involved in human diseases. The following two main projects are funded by separate NIH grants:

1) ”Structure-Function of the HA Receptor for Endocytosis” NIH GM69961

Abstract (link to pdf file)

HA is a major part of extracellular matrices throughout the body, and plays both structural and cell signaling roles in various tissues. For example, HA can regulate cell behavior and migration during development. Humans synthesize and degrade about 5 grams of HA every day.   Sinusoidal endothelial cells in lymph node and liver have a specific endocytic receptor for HA that mediates its clearance, and degradation, from lymph fluid or the blood, respectively. Due to the high viscosity of HA, the failure to remove circulating HA would be harmful.  Recent results suggest that variants of this HA Receptor for Endocytosis (HARE) may have important functions during development, lymphocyte movement in the body and during metastasis of cancer cells.  We have purified and cloned this human membrane receptor and are using molecular biology, cell biology and protein chemistry techniques to understand how it interacts with HA and other glycosaminoglycans.  We are also collaborating with others to determine the role of HARE in various diseases, including cancer.

2) “Structure-Function of Hyaluronan Synthases” NIH GM35978

lAbstract (link to pdf file)

HA synthesis and degradation are abnormal in many diseases, such as arthritis and many cancers. Since we cloned the first HA synthase gene, which encodes the enzyme that makes hyaluronic acid, we have been using recombinant DNA approaches, such as site-directed mutagenesis, to understand how the enzyme catalyzes the alternating polymerization of two different sugars into a polymer of ≥30,000 monomers.  Although the three human HA synthases are involved in many important normal and disease processes, no one has been able to purify and study these proteins in an active form.  That is one of our major goals.  We are studying the streptococcal HA synthases as a model, in order to solve this problem so we can advance our understanding about the role of HA synthases in human health and disease.

Last updated: March 8, 2005

Abbreviated NIH Biosketch for Dr. Weigel (3/2/05).  Biosketch

List of publications from the Weigel research group since 2002.  Publications

Full CV for Dr. Weigel.  CV

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