Brian B Haab

Brian B Haab
Van Andel Research Institute · Cancer and Cell Biology

Ph.D.

About

168
Publications
16,386
Reads
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9,311
Citations
Introduction
We're working on: 1) understanding how specific protein glycoforms change in the development and progression of pancreatic cancer; 2) using that information to form better biomarkers; and 3) developing improved tools for studying glycosylation in clinical samples. Please see our website for information on specific projects and technologies.
Additional affiliations
May 2000 - present
Van Andel Research Institute
Description
  • Faculty
January 1999 - May 2000
Stanford University Scool of Medicine
Position
  • PostDoc Position
December 1998 - April 2000
Stanford University
Description
  • Postdoctoral Fellow
Education
August 1993 - December 1998
University of California, Berkeley
Field of study
  • Chemistry
September 1984 - December 1992
University of Michigan
Field of study
  • Chemistry

Publications

Publications (168)
Article
Full-text available
Molecular markers to detect subtypes of cancer cells could facilitate more effective treatment. We recently identified a carbohydrate antigen, named sTRA, that is as accurate a serological biomarker of pancreatic cancer as the cancer antigen CA19-9. We hypothesized that the cancer cells producing sTRA are a different subpopulation than those produc...
Article
Full-text available
Knowledge of lectin and glycosidase specificities is fundamental to the study of glycobiology. The primary specificities of such molecules can be uncovered using well-established tools, but the complex details of their specificities are difficult to determine and describe. Here we present a language and algorithm for the analysis and description of...
Article
Full-text available
Background and aims: The CA19-9 antigen is the current best biomarker for pancreatic cancer, but it is not elevated in about 25% of pancreatic cancer patients at a cutoff that gives a 25% false-positive rate. We hypothesized that antigens related to the CA19-9 antigen, which is a glycan called sialyl-Lewis A (sLeA), are elevated in distinct subset...
Article
Glycans are critical to protein biology and are useful as disease biomarkers. Many studies of glycans rely on clinical specimens, but the low amount of sample available for some specimens limits the experimental options. Here we present a method to obtain information about protein glycosylation using a minimal amount of protein. We treat proteins t...
Article
Certain experiments involve the high-throughput quantification of image data, thus requiring algorithms for automation. A challenge in the development of such algorithms is to properly interpret signals over a broad range of image characteristics, without the need for manual adjustment of parameters. Here we present a new approach for locating sign...
Article
Full-text available
Proteins that bind carbohydrate structures can serve as tools to quantify or localize specific glycans in biological specimens. Such proteins, including lectins and glycan-binding antibodies, are particularly valuable if accurate information is available about the glycans that a protein binds. Glycan arrays have been transformational for uncovering...
Article
Full-text available
The difficulty in uncovering detailed information about protein glycosylation stems from the complexity of glycans and the large amount of material needed for the experiments. Here we report a method that gives information on the isomeric variants of glycans in a format compatible with analyzing low-abundance proteins. On-chip glycan modification a...
Data
Supporting information for Klamer & Haab et al., Anal Chem 2017
Article
A major challenge in diagnosing and treating pancreatic cancer is the complex diversity between and within tumors in cellular morphologies and behaviors. Molecular markers to detect and classify specific variants of cancer cells could facilitate drug targeting of subtypes of cancer cells. We recently found that a glycan related to the CA19-9 antige...
Data
A4GNT is elevated in the dysplastic epithelia of pancreatic cysts. (PDF)
Data
Reagent information. (PDF)
Data
Patient sample information. (PDF)
Article
Full-text available
Molecular indicators to specify the risk posed by a pancreatic cyst would benefit patients. Previously we showed that most cancer-precursor cysts, termed mucinous cysts, produce abnormal glycoforms of the proteins MUC5AC and endorepellin. Here we sought to validate the glycoforms as a biomarker of mucinous cysts and to specify the oligosaccharide l...
Data
Glycan array analysis of lectin specificities. (PDF)
Article
Recent research has uncovered unexpected ways that glycans contribute to biology, as well as new strategies for combatting disease using approaches involving glycans. To make full use of glycans for clinical applications, we need more detailed information on the location, nature, and dynamics of glycan expression in vivo. Such studies require the u...
Article
Full-text available
The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients,...
Article
The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the...
Article
Full-text available
The glycan array is a powerful tool for investigating the specificities of glycan-binding proteins. By incubating a glycan-binding protein on a glycan array, the relative binding to hundreds of different oligosaccharides can be quantified in parallel. Based on these data, much information can be obtained about the preference of a glycan-binding pro...
Article
Full-text available
The sialyl-Lewis A (sLeA) glycan forms the basis of the CA19-9 assay and is the current best biomarker for pancreatic cancer, but because it is not elevated in ~25% of pancreatic cancers, it is not useful for early diagnosis. We hypothesized that sLeA-low tumors secrete glycans that are related to sLeA but not detectable by CA19-9 antibodies. We us...
Article
Glycan array technology has revolutionized the study of the glycan-binding specificities of lectins. Developers of glycan arrays are continually increasing the diversity and scope of the arrays, bringing the potential to better determine the rules that govern lectin binding. But with this opportunity comes the challenge of increased difficulty in u...
Article
Full-text available
Background: γ-Glutamyl transpeptidase 1 (GGT1) is an N-glycosylated membrane protein that catabolizes extracellular glutathione and other γ-glutamyl-containing substrates. In a variety of disease states, including tumor formation, the enzyme is shed from the surface of the cell and can be detected in serum. The structures of the N-glycans on human...
Article
The aggressiveness of pancreatic cancer is associated with the acquisition of mesenchymal characteristics by a subset of pancreatic cancer cells. The factors driving the development of this subset are not well understood. In this study, we tested the hypothesis that acquisition of a mesenchymal phenotype occurs selectively in tumor cells that harbo...
Article
Full-text available
A recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) method to spatially profile the location and distribution of multiple N-linked glycan species in frozen tissues has been extended and improved for the direct analysis of glycans in clinically derived formalin-fixed paraffin-embedded (FFPE) tissues...
Article
The poor outcome of pancreatic cancer is hypothesized to be due to a subset of cancer cells that have elevated propensity to metastasize and are resistant to current chemotherapeutics. In vitro, the process of epithelial to mesenchymal transition (EMT) has been shown to grant cells with the aforementioned properties. Hence, it has been hypothesized...
Article
Full-text available
This chapter describes methods for the use of antibody microarrays with rolling-circle amplification (RCA). The methods are divided into three sections. The first section covers antibody preparation and microarray production, the second describes the method for using biological samples on antibody microarrays, and the third describes the method for...
Conference Paper
Full-text available
Tumor associated macrophages (TAMs) are considered a critical component of the desmoplastic response, a variable host-tumor response and an ongoing research focus. Research and experimental plans have increased in complexity to better characterize the interactions and biological roles of the components of desmoplasia as a ‘response or a niche’. His...
Article
Currently, pancreatic cancer is the fourth cause of cancer death. In 2013, it is estimated that approximately 38,460 people will die of pancreatic cancer. Early detection of malignant cyst (pancreatic cancer precursor) is necessary to help prevent late diagnosis of the tumor. In this study, we characterized the glycoproteome on pooled mucinous (n=1...
Article
Antibody arrays provide a valuable method for obtaining multiple protein measurements from small volumes of biological samples. Antibody arrays can be designed to target not only core protein abundances (relative or absolute abundances, depending on the availability of standards for calibration), but also posttranslational modifications, provided a...
Article
Lectins are valuable tools for detecting specific glycans in biological samples, but the interpretation of the measurements can be ambiguous due to the complexities of lectin specificities. Here, we present an approach to improve the accuracy of interpretation by converting lectin measurements into quantitative predictions of the presence of variou...
Article
Full-text available
Schistosome parasites follow a complex migration path through various tissues, changing their antigenic profile as they develop. A thorough understanding of the antibody response in each tissue region could help unravel the complex immunology of these developing parasites and aid vaccine design. Here we used a novel strategy for analysing the local...
Article
Full-text available
Purpose: Previously we have shown that specific protein glycoforms may be uniquely informative about the pathological state of a cyst and may serve as accurate biomarkers. Here we tested this hypothesis using antibody-lectin sandwich arrays in broad screens of protein glycoforms and in targeted studies of candidate markers. Experimental design: We...
Article
Full-text available
The development of accurate clinical biomarkers has been challenging in part due to the diversity between patients and diseases. One approach to account for the diversity is to use multiple markers to classify patients, based on the concept that each individual marker contributes information from its respective subclass of patients. Here we present...
Data
Antibody arrays with glycan detection. In this example, three identical arrays containing three different antibodies (AB1, AB2, and AB3) are incubated with plasma, and proteins and captured according to the specificities of each antibody. Each array is probed with a different detection antibody, AB4, AB5, or AB6. The detection antibodies target spe...
Data
Antibodies and reagents used in the microarray experiments. (DOCX)
Article
The glycan array is a powerful tool for investigating the specificities of glycan-binding proteins. By incubating a glycan-binding protein on a glycan array, the relative binding to hundreds of different oligosaccharides can be quantified in parallel. Based on these data, much information can be obtained about the preference of a glycan-binding pro...
Article
Full-text available
Lectin-glycan interactions have critical functions in multiple normal and pathological processes, but the binding partners and functions for many glycans and lectins are not known. An important step in better understanding glycan-lectin biology is to enable systematic quantification and analysis of the interactions. Glycan arrays can provide the ex...
Article
Improved methods for studying glycans could spur significant advances in the understanding and application of glycobiology. The use of affinity reagents such as lectins and glycan-binding antibodies is a valuable complement to methods involving mass spectrometry and chromatography. Many lectins, however, are not useful as analytic tools due to low...
Article
Carbohydrates have fundamental roles throughout biology, yet they have not been as well studied as proteins and nucleic acids, in part due to limitations in the experimental tools. Improved methods for studying glycans could spur significant advances in the understanding and application of glycobiology. The use of affinity reagents, such as lectins...
Article
The CA 19-9 antigen is currently the best individual marker for the detection of pancreatic cancer. In order to optimize the CA 19-9 assay and to develop approaches to further improve cancer detection, it is important to understand the specificity differences between CA 19-9 antibodies and the consequential affect on biomarker performance. Antibody...
Article
Full-text available
Pancreatic cancer cells that have mesenchymal traits can be particularly migratory and resistant to chemotherapeutics. These cells are presumed to represent a more advanced and deadly population of cells relative to cancer cells with more differentiated, epithelial traits. The factors leading to the acquisition of a mesenchymal phenotype in pancrea...
Article
The early detection of a portion of pancreatic cancer precursors_cystic neoplasms of the pancreas_is possible through high-resolution abdominal imaging, providing an opportunity to successfully treat these lesions before they become invasive. The increased use of abdominal imaging has led to a higher rate of identifying pancreatic cysts, but curren...
Article
In this study, we describe an effective protocol for use in a multiplexed high-throughput antibody microarray with glycan binding protein detection that allows for the glycosylation profiling of specific proteins. Glycosylation of proteins is the most prevalent post-translational modification found on proteins, and leads diversified modifications o...
Article
Significant efforts are underway to develop new biomarkers from pancreatic cyst fluid. Previous research has made use of cyst fluid collected from surgically removed cysts, but the clinical implementation of biomarkers would use cyst fluid collected by endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA). The purpose of this study was to...
Data
Selection of antibodies that capture CA 19-9 carrier proteins. a) 12 serum samples (6 benign+6 cancer) were incubated on arrays containing 58 different capture antibodies at detected with the CA 19-9 antibody. A series of steps were taken to select antibodies that capture CA 19-9 carrier proteins and that have potential value in subsequent experime...
Data
Increased sensitivity using markers complementary to total CA 19-9. Data from sample set 1, replicate 1 are presented. a) Comparison of CA19-9 on MUC16 to total CA19-9. The levels of CA 19-9 on MUC16 for each sample are plotted along the vertical axis, and the total CA 19-9 levels for the same samples are plotted along the horizontal axis. The plot...
Data
CA 19-9 immunoblots of selected samples. Of fundamental interest is the distribution of CA 19-9 carrier proteins in these subgroups. An approach to visualize the range of proteins carrying the CA 19-9 antigen is to fractionate the plasma proteins using SDS-PAGE and immunoblot for the CA 19-9 antigen, which we did for representative samples from the...
Data
Antibodies used on the arrays and for detection in the biomarker profiling experiments. (DOCX)
Data
Antibodies used in the large-scale screening for CA 19-9 carrier proteins. (DOCX)
Data
Antibodies used for the follow up experiments in screening for CA 19-9 carrier proteins. (DOCX)
Conference Paper
Full-text available
Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine k...
Article
Full-text available
Background: Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profil...
Article
Full-text available
The current best serum marker for pancreatic cancer, CA 19-9, detects a carbohydrate antigen on multiple protein carriers. Better knowledge of the protein carriers of the CA 19-9 antigen in various disease states may lead to improved diagnostic tests. To identify proteins that carry the CA 19-9 antigen, we immunoprecipitated the CA 19-9 antigen fro...
Article
Full-text available
Glycan-binding proteins are commonly used as analytical reagents to detect the levels of specific glycan structures in biological samples. A detailed knowledge of the specificities of glycan-binding proteins is required for properly interpreting their binding data. A powerful technology for characterizing glycan-binding specificity is the glycan ar...
Article
The antibody-lectin sandwich arrays (ALSA) is a powerful new tool for glycoproteomics research. ALSA enables precise measurements of the glycosylation states of multiple proteins captured directly from biological samples. The platform can be used in a high-throughput mode with low sample consumption, making it well suited to biomarker research expl...
Article
Full-text available
The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of th...
Article
Full-text available
Knowledge on the underlying mechanisms for nonhealing chronic wounds is fragmentary. To increase our understanding of the pathogenesis, the relationship between healing ability and a large panel of proteins was studied using a specially designed wound-healing antibody-based microarray. Wound fluid from nondiabetic patients with nonhealing venous le...