Matthew Hoffman, B.D.S., Ph.D.
Laboratory of Cell and Developmental Biology
Building 30, Room 433
30 Convent Drive
Bethesda, MD 20892
An irreversible loss of salivary gland function often occurs in humans after removal of salivary tumors as a result of Sjogrens syndrome, and in certain rare genetic syndromes affecting fibroblast growth factor receptor (FGFR) signaling. In addition, each year more than 500,000 patients worldwide are treated for head and neck cancer, and exposure of salivary glands in the radiation field results in permanent xerostomia, which is thought to be due to the destruction of the salivary gland stem/progenitor cells. Inevitably, the loss of salivary gland function impairs the oral health of the patients and affects their quality of life. Understanding how salivary glands develop will provide targets for gland regeneration in damaged adult glands. We aim to identify the developmental mechanisms underlying salivary gland organogenesis. We focus on understanding how FGFR signaling is regulated and how microRNAs influence development. Elucidating how FGFR-dependent signal transduction and regulation of gene expression directs stem/progenitor cells along a series of cell fate decisions to form a functional salivary gland is critical to understanding how organogenesis occurs. In addition, salivary gland development also involves interactions between neuronal cells and the epithelial stem/progenitor cell populations. Innervation of the adult salivary glands is essential for secretion and regeneration after damage, and thus successful therapeutic regeneration may require both tissue-specific progenitor cells and/or modulation of neuronal-epithelial cell interactions. We are focused on identifying and studying the stem/progenitor cells in the salivary glands and how their cell fates are controlled during development, which will be useful for planning future regenerative therapy.
Matt Hoffman is the senior investigator in the Matrix and Morphogenesis Section of the Laboratory of Cell and Developmental Biology at the NIDCR. He received his dental degree from the Otago University Dental School in New Zealand. He then worked clinically for 2 years for the Wellington Hospital Board. He did part-time microbiology research while working clinically and received a Fulbright Scholarship for Ph.D. training in the USA. He completed a Ph.D. in microbiology and immunology at the University of Rochester in New York. He began postdoctoral training at NIH and then started his own laboratory at NIDCR in 2004. His laboratory aims to understand the diverse regulatory inputs that drive salivary gland development from the earliest stages of cell commitment, progenitor cell maintenance, and differentiation, to growth and morphogenesis, culminating in the formation of a functional salivary gland. Elucidating how stem/progenitor cells are directed along a series of cell fate decisions to form a functional salivary gland is critical to understanding organogenesis, and provides a template for future regenerative therapy. His lab investigates interactions among the various cell types and their stem/progenitor cells, including the epithelial, neuronal, and mesenchymal cells, and their extracellular matrix (ECM) microenvironment, or niche.
Patel VN, Lombaert IM, Cowherd SN, Shworak NW, Xu Y, Liu J, Hoffman MP. Hs3st3-modified heparan sulfate controls KIT+ progenitor expansion by regulating 3-O-sulfotransferases. Dev Cell. 2014;29(6):662-73.
Hayashi T, Lombaert IM, Hauser BR, Patel VN, Hoffman MP. Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis. Dev Cell. 2017;40(1):95-103.
Knox SM, Lombaert IM, Haddox CL, Abrams SR, Cotrim A, Wilson AJ, Hoffman MP. Parasympathetic stimulation improves epithelial organ regeneration. Nat Commun. 2013;4:1494.
Knosp WM, Knox SM, Lombaert IM, Haddox CL, Patel VN, Hoffman MP. Submandibular parasympathetic gangliogenesis requires sprouty-dependent Wnt signals from epithelial progenitors. Dev Cell. 2015;32(6):667-77.
Knox SM, Lombaert IM, Reed X, Vitale-Cross L, Gutkind JS, Hoffman MP. Parasympathetic innervation maintains epithelial progenitor cells during salivary organogenesis. Science. 2010;329(5999):1645-7.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on September 19th, 2018