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Dr. Jeff Gildersleeve

Dr. Jeff Gildersleeve
Chemical Glycobiology

Research Summary

  • Glycan array technology
  • Cancer biomarkers
  • Cancer vaccines
  • Synthesis of carbohydrate antigens

The Gildersleeve group works at the interface of chemistry, glycobiology, and immunology. We use chemical approaches to 1) aid the design and development of cancer and HIV vaccines, 2) identify clinically useful biomarkers, and 3) better understand the roles of carbohydrates in cancer and HIV immunology. To facilitate these studies, we have developed a glycan microarray that allows high-throughput profiling of serum anti-glycan antibody populations. A number of other groups have also developed glycan arrays; our array is unique in that we use multivalent neoglycoproteins as our 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 work and are uncovering new biomarkers for the early detection, diagnosis, and prognosis of cancer. In particular, we are studying immune responses induced by PROSTVAC-VF, a cancer vaccine in Phase III clinical trials for the treatment of advanced prostate cancer. In addition, we are identifying biomarkers for the early detection and prognosis of ovarian and lung cancer. 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. Please contact Jeff Gildersleeve for more details.

1 - 5 of 51 results

1)  Yin Z, Comellas-Aragones M, Chowdhury S, Bentley P, Kaczanowska K, Benmohamed L, Gildersleeve JC, Finn MG, Huang X.
Boosting Immunity to Small Tumor-Associated Carbohydrates with Bacteriophage Qß Capsids.
ACS Chem. Biol. 8: 1253-62, 2013. [Journal]

2)  Campbell CT, Llewellyn SR, Damberg T, Morgan IL, Robert-Guroff M, Gildersleeve JC.
High-Throughput Profiling of Anti-Glycan Humoral Responses to SIV Vaccination and Challenge.
PLoS ONE. 8: e75302, 2013. [Journal]

3)  Park S, Gildersleeve JC, Blixt O, Shin I.
Carbohydrate microarrays.
Chem Soc Rev. 42: 4310-26, 2013. [Journal]

4)  Zhang Y, Muthana SM, Farnsworth D, Ludek O, Adams K, Barchi JJ, Gildersleeve JC.
Enhanced epimerization of glycosylated amino acids during solid-phase Peptide synthesis.
J. Am. Chem. Soc. 134: 6316-25, 2012. [Journal]

5)  Zhang Y, Li Q, Rodriguez LG, Gildersleeve JC.
An array-based method to identify multivalent inhibitors.
J. Am. Chem. Soc. 132(28): 9653-62, 2010. [Journal]

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