Principal Investigator

Brian B.
Awardee Organization

Van Andel Research Institute
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Subpopulations of Pancreatic Cancer Cells Defined by Glycan Markers

A difficulty in the development of effective treatments against pancreatic cancer is heterogeneity within and between tumors; a subset of cancer cells, rather than all cells in a tumor, is responsible for the behaviors of invasiveness and resistance to death. Drugs that act on the aggressive subpopulations promise to be more effective than drugs that act on the bulk of a tumor, but research to identify such drugs is hampered by the lack of biomarkers to detect, isolate, and study the aggressive subpopulations. The goal of this project is to identify biomarkers of aggressive subpopulations of pancreatic cancer cells. We hypothesize that distinct subtypes of pancreatic cancer cells exist, and that they differ in their invasiveness and resistance to death. We found support for this hypothesis in previous research through the identification of glycan biomarkers of subpopulations of cancer cells with differences in molecular characteristics and behaviors. We will build on the previous results to fully test the possibility that specific glycan markers can be used for detecting subtypes of cancer cells. We posit that aggressive subtypes will be associated with poor outcomes, and that they will display high invasiveness and resistance to death in model systems. To enable a complete evaluation of the candidate markers, we will employ valuable tissue resources such as primary tumors, patient-derived xenografts, and tumor organoids, and we will apply unique and powerful experimental systems—multimarker immunofluorescence and MALDI glycan imaging. Biomarkers that identify the aggressive subtypes of pancreatic cancer cells could pave the way for the development of truly effective therapies. They would provide a way to determine which model systems, or which cells within the models, are the important ones to target, and they would provide companion diagnostics to guide and monitor the use of the targeted therapies. Drugs arising from such research would, for the first time, strike at the critical point—the subset of cells giving rise to the lethal nature of the disease. We are in a good position to produce significant results given the leads from previous research, our technologies and resources, and the team of clinical, technological, and statistical experts.


  • Haab BB, Klamer Z. Advances in Tools to Determine the Glycan-Binding Specificities of Lectins and Antibodies. Molecular & cellular proteomics : MCP. 2020 Feb;19(2):224-232. Epub 2019 Dec 17. PMID: 31848260
  • Klamer Z, Haab B. Combined Analysis of Multiple Glycan-Array Datasets: New Explorations of Protein-Glycan Interactions. Analytical chemistry. 2021 Aug 10;93(31):10925-10933. Epub 2021 Jul 28. PMID: 34319080
  • Black AP, Liang H, West CA, Wang M, Herrera HP, Haab BB, Angel PM, Drake RR, Mehta AS. A Novel Mass Spectrometry Platform for Multiplexed N-Glycoprotein Biomarker Discovery from Patient Biofluids by Antibody Panel Based N-Glycan Imaging. Analytical chemistry. 2019 Jul 2;91(13):8429-8435. Epub 2019 Jun 20. PMID: 31177770
  • Staal B, Liu Y, Barnett D, Hsueh P, He Z, Gao C, Partyka K, Hurd MW, Singhi AD, Drake RR, Huang Y, Maitra A, Brand RE, Haab BB. The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy Over CA19-9 in Pancreatic Cancer Diagnosis. Clinical cancer research : an official journal of the American Association for Cancer Research. 2019 May 1;25(9):2745-2754. Epub 2019 Jan 7. PMID: 30617132
  • Barnett D, Hall J, Haab B. Automated Identification and Quantification of Signals in Multichannel Immunofluorescence Images: The SignalFinder-IF Platform. The American journal of pathology. 2019 Jul;189(7):1402-1412. Epub 2019 Apr 23. PMID: 31026417
  • Klamer Z, Hsueh P, Ayala-Talavera D, Haab B. Deciphering Protein Glycosylation by Computational Integration of On-chip Profiling, Glycan-array Data, and Mass Spectrometry. Molecular & cellular proteomics : MCP. 2019 Jan;18(1):28-40. Epub 2018 Sep 26. PMID: 30257876
  • Blaschke CRK, McDowell CT, Black AP, Mehta AS, Angel PM, Drake RR. Glycan Imaging Mass Spectrometry: Progress in Developing Clinical Diagnostic Assays for Tissues, Biofluids, and Cells. Clinics in laboratory medicine. 2021 Jun;41(2):247-266. Epub 2021 Apr 24. PMID: 34020762
  • Klamer ZL, Harris CM, Beirne JM, Kelly JE, Zhang J, Haab BB. CarboGrove: a resource of glycan-binding specificities through analyzed glycan-array datasets from all platforms. Glycobiology. 2022 Jul 13;32(8):679-690. PMID: 35352123
  • Gao C, Wisniewski L, Liu Y, Staal B, Beddows I, Plenker D, Aldakkak M, Hall J, Barnett D, Gouda MK, Allen P, Drake R, Zureikat A, Huang Y, Evans D, Singhi A, Brand RE, Tuveson DA, Tsai S, Haab BB. Detection of Chemotherapy-resistant Pancreatic Cancer Using a Glycan Biomarker, sTRA. Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Jan 1;27(1):226-236. Epub 2020 Oct 22. PMID: 33093149
  • Liu Y, Kaur S, Huang Y, Fahrmann JF, Rinaudo JA, Hanash SM, Batra SK, Singhi AD, Brand RE, Maitra A, Haab BB. Biomarkers and Strategy to Detect Preinvasive and Early Pancreatic Cancer: State of the Field and the Impact of the EDRN. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020 Dec;29(12):2513-2523. Epub 2020 Jun 12. PMID: 32532830
  • Lu X, McDowell CT, Blaschke CRK, Liu L, Grimsley G, Wisniewski L, Gao C, Mehta AS, Haab BB, Angel PM, Drake RR. Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids. Analytical chemistry. 2023 May 16;95(19):7475-7486. Epub 2023 May 1. PMID: 37126482