matthew renfrowAssociate Professor

Research Areas
IgA nephropathy and the analysis of protein glycosylation in diseases by mass spectrometry


Research Interests

Our group makes use of high resolution Fourier transform mass spectrometry (FT-MS) to analyze the clustered O-glycans found on the immunoglobulin IgA1 as related to the pathogenesis of IgA nephropathy. This includes the site-specific localization and characterization of individual O-glycan chains in serum samples from patients with IgA nephropathy, enzymatic studies of glycosyltransferases, and many other protein biochemistry experiments. Our goal is to identify the aberrant IgA1 O-glycosylation pattern that leads to the mesangial deposits of IgA1-containing immune complexes as well as characterizing the other proteins involved in the pathogenesis of the disease. This may lead to alternative methods for diagnosing and monitoring the disease as well as identifying targets for therapeutic intervention.

matthew renfrow1Glycosylation is one of the most common post-translational modifications of proteins. It is estimated that over half of mammalian proteins are glycosylated. Glycoproteins are vital for a wide range of biological processes including: transporting molecules, production of enzymes, acting as cell attachment-recognition sites, etc. The varying types and structures of glycoproteins allow them to adapt to these diverse functions. There are two types of protein glycosylation, O-linked and N-linked.

matthew renfrow2A variety of proteins are postranslationally modified with clustered sites of O-glycosylation. These are serine and threonine rich stretches within the amino acid sequence that have short O-glycan chains. (The picture to the left shows a stretch of clustered O-glyans on IgA1 hinge region.) Some examples of O-glycosylation include the immunoglobulin A (A1 isotype), mucins, and bacterial cell surface proteins. IgA nephropathy (IgAN, also known as Berger's disease) is the most common primary glomerulonephritis worldwide, with about 20-40% of patients developing end-stage renal failure. It is characterized by mesangial deposits of IgA1-
containing immune complexes. The carbohydrate side chains of IgA1 molecules play a pivotal role in the pathogenesis of IgAN. IgA1 contains a hinge region between the first and second heavy chain constant region domains with a high content of proline, serine, and threonine and usually have three to six O-linked glycan chains. IgAN is an autoimmune disorder that exhibit abnormal glycosylation of serum immunoglobulins (See IgAN). For a given protein with sites of clustered O-glycans, the protein isolated from a single source produces a population of variably O-glycosylated isoforms that we can observe by mass spectrometry. These isoforms usually show a distinct distribution of microheterogeneity in terms of number of chains, the sites of attachment and O-glycan composition at a given amino acid. Characterizing these clustered sites and understanding how thedistributions change under different biological conditions or disease states is an analytical challenge that our lab is tackling.

Education

Graduate School
Ph.D., University of Georgia, Athens, GA

Postdoctoral Fellowship
Florida State University

Contact

Office
McCallum Basic Health Sciences Building
MCLM 570
1918 University Blvd.
Birmingham, AL 35294-0005

Phone
(205) 996-4681

Email
renfrow@uab.edu

Committed to exploring new frontiers in basic and translational research.

The Department of Biochemistry and Molecular Genetics is an integral part of the vibrant biomedical research community at the University of Alabama at Birmingham (UAB). UAB ranks among the top public institutions of higher education in terms of research and training awards. Research conducted by the faculty, staff, and students of the Department of Biochemistry and Molecular Genetics is currently supported by more than $4.3 million per year in extramural, investigator-initiated grants.

Research

The Department of Biochemistry and Molecular Genetics carries out cutting-edge basic and translational research. Research strengths in the department includes cancer biology, chromatin and epigenetic signaling, metabolism and signaling, regulation of gene expression, structural biology, DNA synthesis and repair, and disease mechanisms.

Education

Graduate students and postdoctoral fellows in the Department of Biochemistry and Molecular Genetics are trained to carry out hypothesis-driven research using advanced research techniques. This training will prepare our graduates for a career in not just biomedical research, but also in other diverse fields that require critical thinking. Our faculty also proudly trains professional (MD, DDS, & DO) students, as well as undergraduate students at UAB.

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