Jeffrey C. Gildersleeve, Ph.D.
Senior Investigator
Head, Chemical Glycobiology Section
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.
Link to additional information about Dr. Gildersleeve’s research.
Link to additional information about Dr. Gildersleeve’s research.
Areas of Expertise
1) glycan array technology, 2) cancer biomarkers, 3) cancer vaccines, 4) synthesis of carbohydrate antigens
Contact Info
Jeffrey C. Gildersleeve, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 376, Room 208
Frederick, MD 21702-1201
Ph: 301-846-5699
gildersj@mail.nih.gov (link sends e-mail)
Center for Cancer Research
National Cancer Institute
Building 376, Room 208
Frederick, MD 21702-1201
Ph: 301-846-5699
gildersj@mail.nih.gov (link sends e-mail)
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.
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.
Scientific Focus Areas:
http://pubs.acs.org/doi/full/10.1021/acschembio.6b00244
Chemical Biology, Immunology
Antibodies are used extensively for a
wide range of basic research and clinical applications. While an
abundant and diverse collection of antibodies to protein antigens have
been developed, good monoclonal antibodies to carbohydrates are much
less common. Moreover, it can be difficult to determine if a particular
antibody has the appropriate specificity, which antibody is best suited
for a given application, and where to obtain that antibody. Herein, we
provide an overview of the current state of the field, discuss
challenges for selecting and using antiglycan antibodies, and summarize
deficiencies in the existing repertoire of antiglycan antibodies. This
perspective was enabled by collecting information from publications,
databases, and commercial entities and assembling it into a single
database, referred to as the Database of Anti-Glycan Reagents (DAGR).
DAGR is a publicly available, comprehensive resource for
anticarbohydrate antibodies, their applications, availability, and
quality
Monoclonal antibodies have
transformed biomedical research and clinical care. In basic research,
these proteins are used widely for a myriad of applications, such as
monitoring/detecting expression of biomolecules in tissue samples,
activating or antagonizing various biological pathways, and purifying
antigens. To illustrate the magnitude and importance of the antibody
reagent market, one commercial supplier sells over 50 000 unique
monoclonal antibody clones. In a clinical setting, antibodies are used
frequently as therapeutic agents and for diagnostic applications. As a
result, monoclonal antibodies are a multibillion dollar industry, with
antibody therapeutics estimated at greater than $40 billion annually,
diagnostics at roughly $8 billion annually, and antibody reagents at $2
billion annually as of 2012
Perspectives on Anti-Glycan Antibodies Gleaned from Development of a Community Resource Database
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States
ACS Chem. Biol., Article ASAP
DOI: 10.1021/acschembio.6b00244
Publication Date (Web): May 25, 2016
Copyright © 2016 American Chemical Society
*E-mail: gildersj@mail.nih.gov.
ACS Editors’ Choice – This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
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