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Scientist Spotlight – Brian Cobb, PhD

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Following his heart to question the role that carbohydrates play in the immune response, autoimmune disorders, and immunoregulation, Case Western Reserve University professor, Brian Cobb looks for translational answers at the interface between immunology and glycobiology. His fascination with the potential of developing a drug that would resolve or treat disease began in high school chemistry class. His undergraduate, doctoral, and postdoctoral studies in the field of biochemistry nurtured this curiosity, concentrating initially on molecules, expanding to immunology interactions, and now fully engaging in the field of glycobiology.

“Early on, I had the impression that the people focusing in on carbohydrates are a minority of the people interested in biochemistry and biology. Although glycobiology is still a very underrepresented field, it appeals to my personality.”

The Cobb lab researches the carbohydrates made within the intestine, their interactions with the immune system to promote health and homeostasis, and the regulation of protein glycosylation as a function of immunoprotection. They are known for their contributions to understanding the underlying mechanisms that govern normal microbiota, the beneficial bacteria that are typically present in the colon. While their sight is set on translational research—to better understand those mechanisms and apply corrections to address system malfunctions, preferably in the form of novel therapeutics—they currently are involved in preclinical testing in mouse models and studies with big impact potential for diseases that include asthma and multiple sclerosis.

“To attract the interest of the pharmaceutical industry, you need something that you can’t buy off-the-shelf: you need to develop something that is compositionally novel. We’ve been trying to figure out the details about which molecules are important, how they work, and which ones interact. 15 years into the process, we now feel that we have enough answers to translate this into the clinical space.”

Glycobiology is a technically challenging field. Unlike other biochemistry disciplines that have an arsenal of relatively robust, inexpensive, accessible, and easy-to-use tools, like those for proteins and nucleic acids, the technology needed to determine carbohydrate composition and monosaccharide construction is far more complicated. Often the biggest challenges in academia are funding and other resources, and the Cobb lab struggles with those, too. To move forward, Brian expects the next steps to involve collaboration, likely with a pharma partner, to help advance beyond the preclinical and translate into the clinical space.

“You need to be comfortable with chemistry to work with glycobiology tools. The gold standard tool is still mass spectrometry, which is quite hands-on and a very specialized field unto itself. In the ideal scenario, we need an improved tool set and a way to promote investigation surrounding the big questions.”

There are many unanswered questions in glycobiology, including its full impact on the immune system. Researchers may not pursue those topics because of funding difficulties, access to the necessary technology, and a lack of data. To help make the study of glycans more accessible in the US, the NIH Common Fund in the glycosciences offers a set of resources. Equipped with more tools and resources, Brian believes that he and other glycobiologists will be able to more aggressively translate what they know into more advanced preclinical testing, studies in higher vertebrates, and collaborations with therapeutic potential. In the interim, Brian chooses Vector Labs lectins (which he describes as “reliable and consistent”), immunohistochemistry reagents, and slide mounting reagents for his lab, and will as he continues to examine what glycans are, how they function, and how his work can make a difference in the clinical environment and promote human well-being.

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Edna M. Kunkel