Jeffrey C. Gildersleeve, Ph.D.
Chemical Biology Laboratory
Building 376, Room 208
Frederick, MD 21702-1201
The goal of our group is to understand and exploit anti-carbohydrate immunity to improve cancer and HIV care. We have a special interest in 1) the design and development of cancer and HIV vaccines, 2) the identification of clinically useful biomarkers, and 3) the development of immunotherapies for cancer. To facilitate these studies, we have developed a carbohydrate microarray, or glycan array, that allows high-throughput profiling of serum anti-glycan antibody populations. The array has approximately 500 array components, including a diverse collection of glycans, glycopeptides, and natural glycoproteins. Our array is unique in that we use multivalent neoglycoproteins as our primary array components. This format allows us to readily translate array results to other applications and affords novel approaches to vary glycan presentation.
The main focus of our current and future research is to study the roles of anti-glycan antibodies in the development, progression, and treatment of cancer. These projects are shedding new light on how cancer vaccines and other immunotherapies work and are uncovering new biomarkers for precision medicine. For example, we are studying immune responses induced by PROSTVAC-VF, a therapeutic cancer vaccine in Phase III clinical trials for the treatment of advanced prostate cancer. We have identified several serum biomarkers that may allow physicians to target PROSTVAC-VF to patients that are likely to respond favorably. In addition to our work on vaccines, we are also interested in the development of new antibodies to tumor associated carbohydrate antigens for diagnostic and therapeutic applications. These projects are highly collaborative in nature and are focused on translating basic research from the bench to the clinic.
We rely heavily on glycan array technology to study immune responses to carbohydrates, and we continually strive to improve this technology. First, carbohydrate-protein interactions often involve formation of multivalent complexes. Therefore, presentation is a key feature of recognition. We have developed several new approaches to vary carbohydrate presentation on the surface of the array, including methods to vary glycan density and neoglycoprotein density. Second, we use synthetic organic chemistry to obtain a diverse set of tumor-associated carbohydrates and glycopeptides to populate our array.
Collaborations and Carbohydrate Microarray Screening
We are frequently asked to screen lectins, antibodies, and other entities on our array. Although we are not a core facility and do not provide screening services per se, we are happy to collaborate on many projects, especially those related to cancer. Please contact Jeff Gildersleeve for more details.
Jeff Gildersleeve obtained his B.S. degree in biology in 1993 from the University of California at San Diego. He obtained his Ph.D. degree in organic chemistry at Princeton University under the guidance of Professor Dan Kahne, and completed postdoctoral training with Professor Peter Schultz at The Scripps Research Institute. He began his independent career at the National Cancer Institute in 2003 and is currently a Senior Investigator in the Chemical Biology Laboratory. The Gildersleeve group uses chemical approaches and glycan microarray technology to study the roles of anti-carbohydrate immune responses in the development, progression, and treatment of cancer and HIV. Dr. Gildersleeve is a recipient of the 2006 NCI Director’s Innovation Award and the 2011 David Y. Gin New Investigator Award from the Division of Carbohydrate Chemistry of the American Chemical Society. He also serves on the Editorial Advisory Board of ACS Central Science, the Editorial Board of the Journal of Biological Chemistry, the Editorial Board of Cell Chemical Biology and the Scientific Advisory Board of the Canadian Glycomics Network.
Muthana SM, Gulley JL, Hodge JW, Schlom J, Gildersleeve JC. ABO blood type correlates with survival on prostate cancer vaccine therapy. Oncotarget. 2015;6(31):32244-56.
Campbell CT, Gulley JL, Oyelaran O, Hodge JW, Schlom J, Gildersleeve JC. Humoral response to a viral glycan correlates with survival on PROSTVAC-VF. Proc Natl Acad Sci U S A. 2014;111(17):E1749-58.
Park S, Gildersleeve JC, Blixt O, Shin I. Carbohydrate microarrays. Chem Soc Rev. 2013;42(10):4310-26.
Campbell CT, Gulley JL, Oyelaran O, Hodge JW, Schlom J, Gildersleeve JC. Serum antibodies to blood group A predict survival on PROSTVAC-VF. Clin Cancer Res. 2013;19(5):1290-9.
Zhang Y, Muthana SM, Farnsworth D, Ludek O, Adams K, Barchi JJ Jr, Gildersleeve JC. Enhanced epimerization of glycosylated amino acids during solid-phase peptide synthesis. J Am Chem Soc. 2012;134(14):6316-25.
Related Scientific Focus Areas
This page was last updated on June 15th, 2017