Welcome to the

Haab Laboratory

Overview

Cancer Immunodiagnostics

The first step in treating cancer is diagnosis. This step is challenging because cancer cells can look very much like non-cancer cells, and because so many forms exist even within one type of cancer. The conventional means of diagnosing cancer by imaging and by viewing cells under a microscope often do not give enough information for diagnosis; we need greater detail — measurements of specific molecules that indicate whether cells are cancerous and what type of cancer cell they are.

The Haab Laboratory analyzes blood and tissue samples to find such molecular indicators, or biomarkers, for the diagnosis and prognosis of pancreatic cancer. Their research has led to the discovery of particular types of carbohydrates — also called glycans — that are produced only by certain types of pancreatic cancer cells and that are secreted at high levels into the blood. The lab’s current goals are to define the glycans and proteins that give the most accurate information about pancreatic cancer; and to establish their use as blood tests and cellular assays for examining patients and guiding treatment. These goals are accelerated by the lab’s novel methods of analyzing glycans and proteins in blood, tissue and cell culture samples.

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Our Impact

We’re raising thousands to save millions.

We’re turning hope into action for the millions of people around the world affected by diseases like cancer and Parkinson’s. Find out how you can help us make a difference.

  • 171 studies published from Nov. 1, 2020 to Oct. 1, 2021
  • 68 studies in high-impact journals from Nov. 1, 2020-Oct. 1, 2021
  • 41 clinical trials launched

Brian Haab, Ph.D.

Professor, Department of Cell Biology

Assistant Dean, Van Andel Institute Graduate School

Areas of Expertise

Pancreatic cancer, glycobiology, biomarker development, technology development, microarray methods

Biography

Dr. Haab obtained his Ph.D. in chemistry from the University of California at Berkeley in 1998. He then served as a postdoctoral fellow in the laboratory of Patrick Brown in the Department of Biochemistry at Stanford University. Dr. Haab joined VAI as a Special Program Investigator in May 2000, became a Scientific Investigator in 2004, and was promoted to Senior Scientific Investigator in 2007. He also serves as an assistant dean of Van Andel Institute Graduate School and as an adjunct professor in the Department of Biochemistry and Molecular Biology and the Genetics Program at Michigan State University.

Project 1

Tests to Detect and Diagnose Pancreatic Cancer

The successful treatment of pancreatic cancer critically depends on achieving an accurate and early diagnosis, but this can be frustratingly difficult. Conventional methods of evaluating patients—assessing scans, visual inspection of cells from a biopsy, and weighing behavioral, health, and demographic data—do not have the detail necessary to distinguish between benign and malignant disease or between cancers with vastly different behaviors. Sometimes a physician can see a mass or other unusual feature in the pancreas but is unsure what it is. Is it benign or cancerous? And if it is cancer, what is the best course of treatment?

Our research builds on the concept that molecular-level information will provide details about a condition that are not observable by conventional methods. Molecular biomarkers could provide such information and enable physicians to make accurate diagnoses and develop optimal treatment plans. We are making progress toward this goal for pancreatic cancer. For example, in recent publications in Molecular and Cellular Proteomics and the Journal of Proteome Research, we disclosed carbohydrate-based biomarkers in the blood serum that improve upon the widely used blood test called CA19-9. By using a panel of three or more independent biomarkers, we detected a greater percentage of cancers than we could with any individual biomarker. We are seeking to substantiate those findings and to evaluate their clinical value using serum samples from several clinical sites.

Other research is aimed at further improving the biomarker tests. The results so far suggest that each individual biomarker arises from a distinct subpopulation of cancer patients and from a characteristic cell type. This finding is important because the biomarkers may reveal differences between subgroups of tumors—a possibility we are exploring in the research described below. For the purpose of improving our blood tests, determining the characteristics of the cells that produce each biomarker, as well as of the cells that do not produce any of our biomarkers, will help to optimize a blood test to accurately identify cancers across the entire spectrum of patients.

The ultimate goal is to get the new tests established in clinical laboratories in order to benefit patients. To that end, we are working with industry partners to transfer our biomarker assays to the clinical laboratory setting and to begin analyzing patient samples received consecutively from clinical sites. If we have good results, we hope to initiate clinical trials for the diagnosis of pancreatic cancer and, eventually, for evaluations of surveillance among people at elevated risk for pancreatic cancer.

Better treatment through subtyping

Pancreatic cancer characteristics, such as the cell types within the tumor, the amount of metastasis, the responses to treatments, and overall outcomes, vary greatly among patients. So far, identifying the underlying causes of such differences and predicting the behavior of individual tumors have not been possible. If we could determine what drives the differences between the tumors or identify molecules that help predict the behavior of each tumor, we could establish better treatment plans for each patient or determine the drugs that work best against each subtype.

Our research is revealing major groupings of tumors based on the carbohydrates on the surface of, and in the secretions from, cancer cells. The carbohydrates are related to the CA19-9 antigen and have distinct biological functions. In current research we want to determine the molecular nature of the subgroups of cells and whether the subgroups have different levels of aggressiveness or different responses to particular drugs. We are using new approaches for measuring carbohydrates and proteins in tumor tissue, and we are employing powerful new software—introduced in our recent publication in Analytical Chemistry—to examine the cell types that produce each carbohydrate-based biomarker. We are using that information to evaluate whether certain types of cells predict clinical behavior. As advances and new options in treatments become available, this type of research is increasingly important for guiding clinical decisions. We are working closely with our physician collaborators to evaluate on a case-by-case basis the value of the molecular information and to guide our research toward improving the tests. Ultimately, physicians could use the molecular tests on material from biopsies, surgical resections, or blood samples.

CarboGrove

CarboGrove is a database of the binding specificities of glycan-binding proteins. The results are derived from MotifFinder analysis of glycan array data from a wide variety of glycan array sources. In addition to presenting detailed summaries of lectin and antibody binding, the database offers programmatic access to the data through an API as well as a web server for running MotifFinder.

Visit CarboGrove

MotifFinder

MotifFinder enables the automated analysis of glycan array data. The program provides information about the binding determinants of lectins and glycosidases that were incubated on the arrays. Full descriptions and instructions are provided in the download material.

MotifFinder Request Form

Please fill out the form below to request the MotifFinder software.

MotifFinder Request Form

"*" indicates required fields

Name*
For which purpose do you plan to use MotifFinder?*
This field is for validation purposes and should be left unchanged.

SignalFinder-Microarray

SignalFinder-Microarray (SignalFinderMA) enables the automated analysis of microarray images. SignalFinderMA automatically detects individual spots within a microarray and outputs statistics for each spot and for replicate spots. The program can accommodate multiple arrays within a single image. Full descriptions and instructions are provided in the download material.

SignalFinder-Microarray Request Form

Please fill out the form below to request the SignalFinder-Microarray software.

SignalFinder-Microarray

"*" indicates required fields

Name*
For which purpose do you plan to use SignalFinder-Microarray??*
This field is for validation purposes and should be left unchanged.

SignalFinderIF

SignalFinderIF is the core of the SignalFinder Suite. SignalFInderIF enables the automated analysis of pathology tissues stained with immunofluorescence and imaged with a microscope or digital pathology platform. SignalFinderIF implements the Segment Fit Thresholding (SFT) algorithm to determine and quantify signal objectively from immunofluorescence images. The software provides the ability to select as many channels as are available from the image file as well as multiple thresholds selected as multipliers of the base threshold with user selection of channels, thresholds and multiplier. SignalFinder also allows selection of multiple tissues and provides automated tissue detection for tissue selection from tissue microarrays (TMAs). The software supports multiple image formats and can be quickly adapted to most image formats, upon request.

SignalFinderIF Request Form

Please fill out the form below to request the SignalFinderIF software.

SignalFinderIF

"*" indicates required fields

Name*
For which purpose do you plan to use MotifFinder?*
This field is for validation purposes and should be left unchanged.

SELECTED PUBLICATIONS

For a full list of Dr. Haab’s publications, please visit PubMed.

2022

Klamer ZL, Harris CM, Beirne JM, Kelly JE, Zhang J, Haab BB. 2022. CarboGrove: a resource of glycan-binding specificities through analyzed glycan-array datasets from all platformsGlycobio.

2021

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. 2021. Detection of chemotherapy-resistant pancreatic cancer using a glycan biomarker, sTRA. Clin Cancer Res 27(1):226-236.

Klamer Z, Haab BB. 2021. Combined analysis of multiple glycan-array datasets: New explorations of protein-glycan interactionsAnalyt Chem.

2020

McDowell CT, Klamer Z, Hall J, West CA, Wisniewski L, Powers TW, Angel P, Mehta AS, Lewin DN, Haab BB, Drake R. 2020. Imaging mass spectrometry and lectin analysis of N-linked glycans in carbohydrate antigen defined pancreatic cancer tissuesMol Cell Proteomics 20:100012.
*Highlighted by ASBMBToday

Gao CF, Wisniewski LB, Liu Y, Staal B, Beddows I, Plenker D, Aldakkak M, Hall J, Barnett D, Kheir Gouda M, Allen PJ, Drake RR, Zureikat AM, Huang Y, Evans DB, Singhi AD, Brand RE, Tuveson DA, Tsai S, Haab BB. 2020. Detection of chemotherapy-resistant pancreatic cancer using a glycan biomarker, sTRAClin Cancer Res.

2019

Staal B*, Liu Y*, Barnett D*, Hsueh P, Zonglin H, Gao C, Partyka K, Hurd MW, Singhi AD, Drake RR, Huang Y, Maitra A, Brand RE, Haab BB. 2019. The sTRA plasma biomarker: Blinded validation of improved accuracy over CA19-9 in pancreatic cancer diagnosisClin Cancer Res.

Barnett D, Haab BB. 2019. Automated identification and quantification of signals in multichannel immunofluorescence images: The SignalFinder platformAm J Pathol.

Klamer Z, Hsueh P, Ayala-Talavera D, Haab B. 2019. Deciphering protein glycosylation by computational integration of on-chip profiling, glycan-array data, and mass spectrometryMol Cell Proteomics 18(1):28-40.

2017

Klamer Z, Staal B, Prudden AR, Liu L, Smith DF, Boons GJ, Haab BB. 2017. Mining high-complexity motifs in glycans: A new language to uncover the fine specificities of lectins and glycosidases.
Anal Chem.

Barnett D, Liu Y, Partyka K, Huang Y, Tang H, Hostetter G, Brand RE, Singhi AD, Drake RR, Haab BB. 2017. The CA19-9 and Sialyl-TRA antigens define separate subpopulations of pancreatic cancer cellsSci Rep 7:4020.

2016

Reatini BS, Ensink E, Liau B, Sinha JY, Powers TW, Partyka K, Bern M, Brand RE, Rudd PM, Kletter D, Drake RR, Haab BB. 2016. Characterizing protein glycosylation through on-chip glycan medication and probingAnal Chem.

Tang H, Partyka K, Hsueh P, Sinha JY, Kletter D, Zeh H, Huang Y, Brand RE, Haab BB. 2016. Glycans related to the CA19-9 antigen are elevated in distinct subsets of pancreatic cancers and improve diagnostic accuracy over CA19-9Cell Mol Gastroenterol Hepatol 2(2):201–215. 

2015

Haab BB, Huang Y, Balasenthil S, Partyka K, Tang H, Anderson M, Allen P, Sasson A, Zeh H, Kaul K, Kletter D, Ge S, Bern M, Kwon R, Blasutig I, Srivastava S, Frazier ML, Sen S, Hollingsworth MA, Rinaudo JA, Killary AM, Brand RE. 2015. Definitive characterization of CA 19-9 in resectable pancreatic cancer using a reference set of serum and plasma specimensPLoS One. 10(10):e0139049.

Ensink E, Sinha J, Sinha A, Tang H, Calderone HM, Hostetter G, Winter J, Cherba D, Brand RE, Allen PJ, Sempere LF, Haab BB. 2015. Segment and fit thresholding: A new method for image analysis applied to microarray and immunofluorescence dataAnal Chem 87(19):9715–9721.

Tang H, Hsueh P, Kletter D, Bern M, Haab BB. 2015. The detection and discovery of glycan motifs in biological samples using lectins and antibodies: new methods and opportunitiesAdv Cancer Res 126:167–202.

Kletter D, Curnutte B, Maupin K, Bern M, Haab BB. 2015. Exploring the specificities of glycan-binding proteins using glycan array data and the GlycoSearch softwareMethods Mol Biol 1273:203–214.

Tang H, Singh S, Partyka K, Kletter D, Hsueh P, Yadav J, Ensink E, Bern M, Hostetter G, Hartman D, Huang Y, Brand RE, Haab BB. 2015. Glycan motif profiling reveals plasma sialyl-Lewis X elevations in pancreatic cancers that are negative for CA 19-9Mol Cell Proteomics 14(5):1323–1333.

Singh S, Pal K, Yadav J, Tang H, Partyka K, Kletter D, Hsueh P, Ensink E, Birenda KC, Hostetter G, Xu H, Bern M, Smith D, Mehta A, Brand R, Melcher K, Haab BB. 2015. Upregulation of glycans containing 31 fucose in a subset of pancreatic cancers uncovered using fusion-tagged lectinsJ Proteome Res 14(6):2594–605.

2014

Powers TW, Neely BA, Shao Y, Tang H, Troyer DA, Mehta AS, Haab BB, Drake RR. MALDI imaging mass spectrometry profiling of N-glycans in formalin-fixed paraffin embedded clinical tissue blocks and tissue microarraysPLoS One 9(9):e106255.

Kletter D, Bern M, Haab BB. 2014. Mining and using glycan array data with the GlycoSearch analysis program and GlycanBinder database. In: Naoyuki Taniguchi, T. E., Gerald Hart, Peter Seeberger, Chi-Huey Wong, ed. Glycoscience: Biology and Medicine, Springer, Japan.

Sinha A, Cherba D, Bartlam H, Lenkiewicz E, Evers L, Barrett MT, Haab BB. 2014. Mesenchymal-like pancreatic cancer cells harbor specific genomic alterations more frequently than their epithelial counterpartsMol Oncol 8(7):1253–1265.

Partyka K, Wang S, Zhao P, Haab BB. 2014. Array-based immunoassays with rolling-circle amplification detectionMethods Mol Biol 1105: 3–15.

Gbormittah FO, Haab BB, Partyka K, Garcia-Ott C, Hincapie M, Hancock WS. 2014. Characterization of glycoproteins in pancreatic cyst fluid using a high performance multiple lectin affinity chromatography platformJ Proteome Res 13(1): 289–299.

2013

Cao Z, Maupin K, Curnutte B, Fallon B, Feasley CL, Brouhard E, Kwon R, West CM, Cunningham J, Brand R, Castelli P, Crippa S, Feng Z, Allen P, Simeone DM, Haab BB. 2013. Specific glycoforms of MUC5AC and endorepellin accurately distinguish mucinous from non-mucinous pancreatic cystsMol Cell Proteomics 12(10): 2724–2734.

McCarter C, Kletter D, Tang H, Partyka K, Ma Y, Singh S, Yadav J, Bern M, Haab BB. 2013. Prediction of glycan motifs using quantitative analysis of multi-lectin binding: motifs on MUC1 produced by cultured pancreatic cancer cellsProteomics Clin Appl 7(9–10): 632–641.

Kletter D, Cao Z, Bern M, Haab BB. 2013. Determining lectin specificity from glycan array data using motif segregation and the GlycoSearch softwareCurr Protoc Chem Biol 5(2): 157–169.

Haab BB, Partyka K, Cao Z. 2013. Using antibody arrays to measure protein abundance and glycosylation: considerations for optimal performanceCurr Protoc Protein Sci 73: Unit 27.6.

Fallon BP, Curnutte B, Maupin KA, Partyka K, Choi S, Brand RE, Langmead CJ, Tembe W, Haab BB. 2013. The Marker State Space (MSS) method for classifying clinical samplesPLoS One 8(6):e65905.

Kletter D, Singh S, Bern M, Haab BB. 2013. Global comparisons of lectin-glycan interactions using a database of analyzed glycan array data. Molecular & Cellular Proteomics 12(4):1026–1035.

Cao Z, Partyka K, McDonald M, Brouhard E, Hincapie M, Brand RE, Hancock WS, Haab BB. 2013. Modulation of glycan detection on specific glycoproteins by lectin multimerizationAnal Chem 85(3):1689–1698.

2012

Haab BB. 2012. Using lectins in biomarker research: addressing the limitations of sensitivity and availabilityProteomics Clin Appl 6(7-8):346–350.

Maupin KA, Liden D, Haab BB. 2012. The fine-specificity of mannose-binding and galactose-binding lectins revealed using outlier-motif analysis of glycan array dataGlycobiology 22(1):160–169.

Partyka K, Maupin KA, Brand RE, Haab BB. 2012. Diverse monoclonal antibodies against the CA 19-9 antigen show variation in binding specificity with consequences for clinical interpretationProteomics 12(13): 2212–2220.

Partyka K, McDonald M, Maupin KA, Brand R, Kwon R, Simeone DM, Allen P, Haab BB. 2012. Comparison of surgical and endoscopic sample collection for pancreatic cyst fluid biomarker identificationJ Proteome Res 11(5): 2904–2911.

2011

Yue T, Maupin K, Fallon B, Li L, Partyka K, Anderson M, Brenner DE, Kaul K, Zeh H, Moser AJ, Simeone DM, Feng Z, Brand RE, Haab BB. 2011. Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriersPLoS One 6(12): e29180.

Yue T, Partyka K, Maupin K, Hurley M, Andrews P, Kaul K, Moser JA, Zeh H, Brand RE, Haab BB. 2011. Identification of blood-protein carriers of the CA 19-9 antigen and characterization of prevalence in pancreatic diseasesProteomics 11(18):3665–3674.

2010

Bergsma D, Buchweitz J, Chen S, Gerszten R, Haab BB. 2010. Antibody-array interaction mapping, a new method to detect protein complexes applied to the discovery and study of serum amyloid P interactions with kininogen in human plasmaMol Cell Proteomics 9(3): 446–456.

Haab BB. 2010. Antibody-lectin sandwich arrays for biomarker and glycobiology studiesExpert Rev Proteomics 7(1): 9–11.

Haab BB, Porter A, Yue T, Li L, Scheiman J, Anderson MA, Barnes D, Schmidt CM, Feng Z, Simeone DM. 2010. Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasmsAnn Surg 251(5): 937–945.

Maupin KA, Sinha A, Eugster E, Miller J, Ross J, Paulino V, Keshamouni VG, Tran N, Berens M, Webb C, Haab BB. 2010. Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systemsPLoS One 5(9): e13002.

Porter A, Yue T, Heeringa L, Day S, Suh E, Haab BB. 2010. A motif-based analysis of glycan array data to determine the specificities of glycan-binding proteinsGlycobiology 20(3): 369–380.

Zeng Z, Hincapie M, Haab BB, Hanash S, Pitteri SJ, Kluck S, Hogan JM, Kennedy J, Hancock WS. 2010. The development of an integrated platform to identify breast cancer glycoproteome changes in human serumJ Chromatogr A 1217(19): 3307–3315.

2009

Hung KE, Faca V, Song K, Sarracino DA, Richard LG, Krastins B, Forrester S, Porter A, Kunin A, Mahmood U, Haab BB, Hanash SM, Kucherlapati R. 2009. Comprehensive proteome analysis of an Apc mouse model uncovers proteins associated with intestinal tumorigenesisCancer Prev Res (Phila) 2(3): 224–233.

Shao C, Chen S, Chen L, Cobos E, Wang JS, Haab BB, Gao W. 2009. Antibody microarray analysis of serum glycans in esophageal squamous cell carcinoma cases and controlsProteomics Clin Appl 3(8): 923–931.

Wu YM, Nowack DD, Omenn GS, Haab BB. 2009. Mucin glycosylation is altered by pro-inflammatory signaling in pancreatic cancer cellsJ Proteome Res 8(4):1876–1886.

Yue T, Goldstein IJ, Hollingsworth MA, Kaul K, Brand RE, Haab BB. 2009. The prevalence and nature of glycan alterations on specific proteins in pancreatic cancer patients revealed using antibody-lectin sandwich arraysMol Cell Proteomics 8(7): 1697–1707.

2007

Chen S, LaRoche T, Hamelinck D, Bergsma D, Brenner D, Simeone D, Brand RE, Haab BB. 2007. Multiplexed analysis of glycan variation on native proteins captured by antibody microarraysNat Methods 4(5): 437–444.

Forrester S, Hung KE, Kuick R, Kucherlapati R, Haab BB. 2007. Low-volume, high-throughput sandwich immunoassays for profiling plasma proteins in mice: identification of early-stage systemic inflammation in a mouse model of intestinal cancerMol Oncol 1(2): 216–225.

Forrester S, Qiu J, Mangold L, Partin A, Misek D, Phinney B, Whitten D, Andrews P, Diamandis D, Omenn GS, Hanash S, Haab BB. 2007. An experimental strategy for quantitative analysis of the humoral immune response to prostate cancer antigens using natural protein microarraysProteomics Clin Appl 1(5): 494–505.

David Ayala-Talavera

Assistant Research Technician

ChongFeng Gao, Ph.D.

Senior Research Scientist

Johnathan Hall

Research Data Technician

Zachary Klamer

Bioinformatics Analyst II

Taylor Klein

Student Intern

Abigail Pearch

Student Intern

Alfredo Reyes Oliveras

Van Andel Institute Graduate School Student

Thesis: Linking glycosylation changes in pancreatic cancer with metabolic dependencies

Ben Staal

Research Associate

Jeanie Wedberg

Senior Administrative Assistant II

PAST LAB MEMBERS

Daniel Barnett, B.A., B.S.

Graduate Student

Anna Barry

Student Intern

Schyler Bennet

Student Intern

Ricardo Burke

Student Intern

Nicole Burmeister

Student Intern

Collete Charlton

Student Intern

Lindsey Furness

Student Intern

Peter Hsueh, B.S.

Graduate Student

Hannah Kalee

Student Intern

Ying Liu, Ph.D.

Research Associate

Kevin A. Maupin, Ph.D.

Postdoctoral Fellow

Katie Partyka, B.S.

Senior Research Technician

Bikash Rana

Student Intern

Hannah VanDusen

Student Intern

Luke Wisniewski

Senior Research Technician