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Dr. Jeff Gildersleeve

Dr. Jeff Gildersleeve
Chemical Glycobiology

Research Summary

  • Glycan array technology
  • Cancer biomarkers
  • Cancer vaccines
  • Anti-glycan antibodies
  • Synthesis of carbohydrate antigens

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.
1 - 5 of 61 results

1)  Gibadullin Ruslan, Farnsworth David Wayne, Barchi Joseph J, Gildersleeve Jeffrey C.
GalNAc-Tyrosine Is a Ligand of Plant Lectins, Antibodies, and Human and Murine Macrophage Galactose-Type Lectins.
ACS Chem. Biol. 2017. [Journal]

2)  Lubkowski Jacek, Durbin Sarah V, Silva Mariana C C, Farnsworth David, Gildersleeve Jeffrey C, Oliva Maria Luiza V, Wlodawer Alexander.
Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth.
FEBS J. 284: 429-450, 2017. [Journal]

3)  Xia Li, Schrump David S, Gildersleeve Jeffrey C.
Whole-Cell Cancer Vaccines Induce Large Antibody Responses to Carbohydrates and Glycoproteins.
Cell Chem Biol. 23: 1515-1525, 2016. [Journal]

4)  Sterner Eric, Flanagan Natalie, Gildersleeve Jeffrey C.
Perspectives on Anti-Glycan Antibodies Gleaned from Development of a Community Resource Database.
ACS Chem. Biol. 11: 1773-83, 2016. [Journal]

5)  Muthana Saddam M, Gildersleeve Jeffrey C.
Factors Affecting Anti-Glycan IgG and IgM Repertoires in Human Serum.
Sci Rep. 6: 19509, 2016. [Journal]