Drexel University - Comprehensive, integrated academics enhanced by co-operative education, technology, and research opportunities. | Drexel University
Drexel University
Search events. View events.

All Categories

Click for help in using calendar displays. Print the contents of the current screen.
Display Format: 
Event Details
Notify me if this event changes.Add this event to my personal calendar.
Go Back
The Biological Roles of Glycoconjugates in Inflammation and Cancer Biology: O-Glycans Rule
Start Date: 5/24/2017Start Time: 4:00 PM
End Date: 5/24/2017End Time: 5:30 PM

Event Description
BIOMED Seminar

The Biological Roles of Glycoconjugates in Inflammation and Cancer Biology: O-Glycans Rule

Richard D. Cummings, PhD
Professor of Surgery
Beth Israel Deaconess Medical Center
Harvard Medical School Center for Glycoscience

Oligosaccharides (glycans) are linked to specific amino acids in most secreted and cell surface proteins. Such glycoproteins and their glycans function both as direct recognition molecules, where they are bound by a wide variety of glycan-binding proteins (GBPs), including animal cell receptors, microbial adhesins lectins and toxins, but glycans can also function indirectly in glycoproteins to facilitate intra- and intermolecular interactions that maintain homeostasis and biological integrity. In studying such glycan functions, we have exploited information from human genetics, ad well as generating specific mutations in biosynthetic pathways to create novel murine models, most notably in regard to O-glycan biosynthesis (R-GalNAc-O-Ser/Thr glycans). Normal synthesis of such O-glycans in animals requires the action of the T-synthase to generate the core 1 O-glycan from the Tn antigen precursor GalNAc1-Ser/Thr. Normal extended O-glycans are recognized by key GBPs, including P-selectin and L-selectin. Such specific recognition of O-glycans by these GBPs directly regulates many cellular interactions and signaling pathways important in development, morphogenesis and organ development.

In terms of additional functions of O-glycans, we have exploited our discovery that the T-synthase requires a specific protein chaperone, termed Cosmc, encoded on the X-chromosome. Cosmc, a resident protein in the endoplasmic reticulum, directly interacts with the newly synthesized T-synthase to facilitate folding to the active form of the enzyme, that subsequently moves to its functional location in the Golgi apparatus. Thus, Cosmc is the key regulator of Tn antigen expression, and loss of Cosmc, through epigenetic silencing, gene mutations and other pathways, and acquired changes in Cosmc function cause Tn expression in many human tumors and tumor cell lines and in Tn syndrome patients. Targeted deletion of Cosmc leads to loss of normal O-glycans, expression of the Tn and sialyl Tn antigens, and multiple pathological consequences, including colorectal cancer.

In this presentation the loss of Cosmc leading to the expression of the Tn antigen has been explored in the gastrointestinal tract, where it leads to pathology, chronic inflammation, and changes in the gut microbiome, and in other cell types, such as T cells and B cells, where loss of Cosmc alters cellular maturation and functionalities. Our studies are revealing the multiple ways in which O-glycans in humans, animals, and other organisms interact within the larger protein-glycan interactome to regulate biological processes. [This work was supported by NIH grants U01CA168930 and P41GM103694 to R. D.C. ]

Richard D. Cummings, PhD, is Professor of Surgery at Harvard Medical School, Beth Israel Deaconess Medical Center, Chair of the Research Council of the Department, Associate Director of the Center for Drug Discovery and Translational Research, and Vice Chair of the Department for Basic and Translational Research. He is also Director of the NIH-supported National Center for Functional Glycomics, Chair of the international Consortium for Functional Glycomics, and is the Director of the newly designated Harvard Medical School Center for Glycoscience.

Dr. Cummings’ research focuses on the roles of complex glycoconjugates and carbohydrates in regulating the fundamental biological processes of cell adhesion and signaling, cancer, pathogenesis by microbes and parasites, and animal development. His research also has a translational focus and he has helped to develop new drugs for treating inflammatory diseases, as well as developing glycan microarray technologies as key tools for exploring glycan recognition and function. As an outgrowth of his translational research, Dr. Cummings also Co-Founded Selexys Pharmaceuticals Inc., a private company developing new treatments for Sickle Cell Disease and inflammatory bowel diseases.

Dr. Cummings has published over 300 peer-reviewed articles, is a Co-Editor of the textbook Essentials of Glycobiology (1st, 2nd and 3rd Editions (1999, 2009 and 2017) and other books in the glycoscience field, and has 29 issued US Patents in the glycosciences. Cummings received his PhD from the Johns Hopkins University and did his post-doctoral fellowship in hematology/oncology at the Washington University School of Medicine in St. Louis. Prior to coming to Harvard he was the Chair of the Department of Biochemistry at the Emory University School of Medicine.
Contact Information:
Name: Ken Barbee
Phone: 215-895-1335
Email: barbee@drexel.edu
Richard Cummings
Papadakis Integrated Sciences Building (PISB), Room 120, located on the northeast corner of 33rd and Chestnut Streets.
  • Undergraduate Students
  • Graduate Students
  • Faculty
  • Staff

  • Display Month:

    Advanced Search (New Search)
    Date Range:
    Time Range:

    Special Features: 

    Select item(s) to Search

    Select item(s) to Search
    Select item(s) to Search
    Select item(s) to Search