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2013 Scientific Report

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Brian B. Haab, Ph.D.

Brian B. Haab, Ph.D. Laboratory of Cancer Immunodiagnostics Dr. Haab earned his Ph.D. in chemistry from the University of California, Berkeley in 1998, after which he was a postdoctoral fellow in the laboratory of Patrick Brown in the Department of Biochemistry at Stanford University. Dr. Haab joined VARI in May 2000 and was promoted to Associate Professor in 2007. From left, front row: Nelson, Partyka, Bartlam, Tang, Brouhard, Ma; back row: McDonald, Curnutte, Sinha, Haab, Cao, Westra Staff Betsy Brouhard, B.S. Zheng Cao, Ph.D. Bryan Curnutte, B.S. Amy Nelson Katie Partyka, B.S. Huiyuan Tang, Ph.D. Students Heather Bartlam, B.S. Yinjiao Ma, M.S. Mitch McDonald Arkadeep Sinha, B.S. Hannah Westra Visiting Scientist David Nowack, Ph.D. 25

Van Andel Research Institute | Scientific Report Research Interests The Haab laboratory studies pancreatic cancer, with the aims of identifying molecular factors that characterize and promote cancer progression and of using this information to more accurately diagnose and guide the treatment of pancreatic cancer. Diagnostics for pancreatic cancers Modern medicine increasingly relies on detailed molecular information to make accurate diagnoses and treatment decisions. A molecular-level understanding of healthy versus diseased human tissue promises to provide much more information about the patient than conventional clinical approaches. The development of improved tools for assessing pancreatic cancer is one of our main goals. For certain patients, there are serious difficulties in distinguishing pancreatic cancer from benign conditions of the pancreas. Some patients have abnormalities that are difficult to diagnose using imaging and biopsy procedures, and the diagnostic work-up process can be highly invasive, costly, and even after using all available methods, inconclusive. A blood test that could clearly resolve the differences between malignant and benign conditions of the pancreas would alleviate this situation. We are working to develop such a blood test based on changes to the carbohydrates (glycans) that are abnormally produced in pancreatic cancers. These structures are attached to a variety of proteins, some of which are secreted and detectable in the blood. An FDA-approved test is available for the CA 19-9 antigen, the most common carbohydrate antigen made by pancreatic cancers, but that test has limited value because some 20% of cancers produce low amounts of CA 19-9. Our studies have shown that the cancers that do not produce much CA 19-9 instead overproduce other structures, and we propose that assays to detect the alternate structures plus the CA 19-9 antigen will accurately identify a higher percentage of cancer patients. We are working with our clinical collaborators at the University of Pittsburgh, the University of Michigan, and in Grand Rapids to test this strategy. Another diagnostic problem is found with patients who have fluid-filled openings, known as pancreatic cysts, within their pancreas. Some cysts are unlikely to ever develop into cancer, while others may progress rapidly to cancer. Current diagnostic methods can not clearly differentiate these types. We are working with our collaborators to analyze the proteins and carbohydrates in fluid collected from the cysts, which could result in tests to determine which patients should have those cysts removed. We also are applying these approaches to related problems in pancreatic cancer, such as determining which patients should have surgery as opposed to chemotherapy only, and monitoring how well a patient is responding to treatment. A future goal is to use our new markers to detect incipient disease among people at a high risk for developing pancreatic cancer, such as those with predisposing genetic characteristics. Glycans in pancreatic ductal adenocarcinoma The goals described above will be advanced by further characterizing the changes in glycans as cancer cells develop and by understanding the cellular processes that result in those changes. We are using novel tools (described below) as well as powerful mass-spectrometry methods to compare the carbohydrates between tumors that produce CA 19-9 and those that do not. In addition, we are controlling the production of CA 19-9 in cultured cells or in mouse hosts to identify what carbohydrate structures are produced when CA 19-9 production is reduced. That control is based on manipulating specific genes involved in the production of CA 19-9. Our aim is to determine which genes are most important in producing the glycan structures. 26

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