Our Science – Gildersleeve Website

Jeffrey C. Gildersleeve, Ph.D.

Laboratory of Medicinal Chemistry Head, Chemical Biology Section Investigator Building 376, Room 109 National Cancer Institute Frederick, MD 21702-1201 Phone:   301-846-5699 Fax:   301-846-6033 E-Mail:   gildersleevej@ncifcrf.gov

Biography

Jeff Gildersleeve began his professional training in sunny southern California at the University of California at San Diego. He graduated in 1993 with a B.S. degree in biology and then moved to New Jersey to pursue a Ph.D. in organic chemistry at Princeton University. Under the guidance of Professor Dan Kahne, his graduate training focused on mechanistic organic chemistry, carbohydrate chemistry, and chemical biology. After completing his Ph.D., he headed back to southern California where he worked with Professor Peter Schultz at The Scripps Research Institute. His postdoctoral work focused on directed evolution of protein catalysts and the development of high-throughput screens for protein catalysts such as catalytic antibodies. In the summer of 2003, he completed one more 3000 mile shot across the heartland and began his current position as a tenure-track Principal Investigator in the Laboratory of Medicinal Chemistry.

Research

Research Interests: Carbohydrate Chemistry and Glycobiology
- Development and Applications of Carbohydrate Microarrays
- Synthesis of Carbohydrate Tumor Antigens
- Development of Carbohydrate-Based Cancer Vaccines, Diagnostic Agents, and Therapeutic Agents.
- Identification of Cancer Biomarkers Using Carbohydrate Microarray Technology

During the onset and progression of cancer, cells undergo dramatic changes in carbohydrate expression. Over the last 30 years, dozen of tumor associated carbohydrate antigens (carbohydrate epitopes that are highly over-expressed or uniquely expressed on tumors) have been identified such as the Tn antigen, Lewis Y, and sialyl-Lewis A (CA19-9). As a result, there has been significant interest in understanding why these changes occur and how they contribute to the disease. Since the changes occur on the cell surface and/or on secreted glycoproteins, they are also interesting targets for the development of diagnostics, vaccines, and imaging agents. After decades of research, however, the biological roles of most carbohydrate antigens are only beginning to be understood. Moreover, efforts to exploit changes in carbohydrate expression for therapeutic benefit have only been successful in a limited number of cases.

While many methods exist for studying carbohydrate-protein interactions, none are well-suited for evaluating hundreds or thousands of potential interactions. As a result, it has been difficult to determine if a particular protein is a carbohydrate-binding protein, to identify carbohydrate ligands to modulate biological processes, and to develop carbohydrate-binding antibodies as research and diagnostic tools. Our group has developed a carbohydrate microarray, also referred to as a glycan array, for high throughput evaluation of carbohydrate-protein interactions. The array contains over 100 different carbohydrate structures and glycoproteins immobilized on a glass microscope slide. Each component is spotted down using a robotic microarray printer. To maximize throughput, the array contains 16 wells with an entire array printed in each well (see photos in the Gallery section).

We are using the carbohydrate microarray to evaluate the specificity of antibodies and lectins, to develop new antibodies with improved binding, and to identify new carbohydrate-binding proteins. In addition, the microarray is being used to monitor changes in serum levels of anti-glycan antibodies as biomarkers for cancer.

One of the major challenges for development of a glycan array is obtaining a diverse set of carbohydrates for the array. Our group relies heavily on synthetic organic chemistry to acquire homogeneous, structurally-defined oligosaccharides for the array. In support of this, we also develop better synthetic methods for obtaining many oligosaccharides.

This page was last updated on 7/3/2008.