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Stanford Tumor Glycome Laboratory — a new initiative of University's postgenomics research

     

 


The Stanford University research team led by Denong Wang, MD, PhD (photo), has been selected by the National Cancer Institute to establish a Tumor Glycome Laboratory to study how changes in carbohydrate structure may play a major role in the progression of prostate cancer and how immune systems recognize and react to cancer-associated complex carbohydrates.

The Stanford Tumor Glycome Laboratory is one of seven such NCI-funded labs nationwide that will share $15.5 million over five years to discover, develop and validate cancer biomarkers (molecular biological indicators) by targeting the carbohydrate (glycan, or sugar) structures on cancer cells. The other six labs will focus on glycan-based biomarkers for melanoma, breast, ovarian, lung, colon and pancreatic cancers.

Dr. Wang, who is director of the Carbohydrate Microarray Laboratory at Stanford, is the principal investigator for the University’s arm of the study. Dr. Wang was instrumental in the development of carbohydrate-based microarray technology that helps scientists to look at the carbohydrate signatures of microorganisms, cancers and other human cells, such as stem cells.

“Scientists have long recognized that certain sugar structures, which are attached to protein and lipid [fat] molecules, may be important as markers for cancer development,” said NCI director John E. Niederhuber, MD. “While this area has compelling scientific interest, its biological and chemical complexities have often discouraged investigation. Today, with the advent of advanced technologies to conduct protein and carbohydrate chemistry, research into this intriguing area has experienced renewed interest.”

Carbohydrates are involved in such important cell processes as recognition, adhesion and signaling, functions that are vital to normal growth and development, tissue repair, pathogen (disease-causing microorganism) invasion and tumor progression. Compared to molecular proteins, molecular carbohydrates are extremely diverse and abundantly present on the surfaces of cells that are readily reactive with other biological molecules.

During the onset and progression of cancer, cells undergo dramatic changes in carbohydrate expression (production). Studies comparing normal and cancer cells have shown that changes in carbohydrate structures on certain protein molecules correlate with cancer development.
As a result, there has been significant interest in understanding why these changes occur and how they contribute to the development of cancer. 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.

Wang’s team developed a carbohydrate microarry, also referred to as a glycan array, for high-throughput evaluation of carbohydrate-protein interactions. The array contains hundreds of different carbohydrate structures and glycoproteins immobilized on a glass microscope slide. Each component is applied using a robotic microarry printer.

Carbohydrate microarrays contain many different carbohydrate epitopes (molecular types) immobilized on a glass microscope slide. The microarray format allows scientists to rapidly evaluate binding of proteins, cells and/or viruses to a wide range of carbohydrates in a high-throughput fashion.

The goals of Tumor Glycome Laboratory are identification and characterization of carbohydrate-based immunological markers of human cancers, as well as development of highly sensitive assays for clinical and research applications. The current focus of the lab group’s work is glycan markers of prostate cancers and anti-glycan autoantibody signatures in prostate cancer patients.

Wang and his colleagues are using high-throughput platforms of carbohydrate microarrays and neoglycolipid (NGL) technology coupled with mass spectrometry for carbohydrate ligand discovery and flow cytometry (Hi-D FACS) for highly sensitive detection of cell and serum markers.

The Stanford Tumor Glycome Laboratory comprises four basic components that function as a team. Key personnel of each component are listed below:

Biomarker Discovery Component

Denong Wang, MD, PhD, principal investigator, genetics, Stanford University
Leonard A. Herzenberg, PhD, professor emeritus in genetics; co-investigator, genetics, Stanford University

Carbohydrate Analytical Component

Ten Feizi, co-principal investigator, Imperial College London

Clinical Specimen Component

Donna Peehl, PhD, professor of urology; co-investigator, urology, Stanford University
Thomas Stamey, MD, professor of urology; co-investigator, urology, Stanford University

Statistical Support Component

Philip W. Lavori, PhD, professor of health research and policy; co-investigator, Cancer Center, Stanford University
Leonore A. Herzenberg, PhD, professor of genetics; co-investigator, genetics, Stanford University

The Tumor Glycome Laboratories are the major component of the new trans-National Institutes of Health Alliance of Glycobiologists for Detection of Cancer and Cancer Risk (http://prevention.cancer.gov/programs-resources/groups/cb/programs/glycome). The other members of the Alliance are the Consortium for Functional Glycomics, supported by the National Institute of General Medical Sciences, and the Glycomics and Glycotechnology Resource Centers, supported by the National Center for Research Resources.

Dr. Wang's contact information at Stanford:

Denong Wang, MD, PhD
Carbohydrate Microarry Laboratory and the Herzenberg Laboratory
Departments of Genetics, Neurology and Neurological Sciences
Stanford University School of Medicine
Beckman Center B011, Stanford, CA 94305-5318
Email: dwang1@stanford.edu

 

Posted on 10/18/07

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