Chief, Matrix and Morphogenesis Section
NATIONAL INSTITUTES OF HEALTH/NIDCR
BUILDING 30 ROOM 433
30 CONVENT DR MSC 4370
BETHESDA MD 20892-4370
Phone: (301) 496-1660
Fax: (301) 402-0897
E-mail: Dr. Matthew P. Hoffman
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.
Research Interests/Scientific Focus
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.
Patel, V.N., Lombaert, I.M., Cowherd, S.N.,
Shworak, N.W., Xu, Y., Liu, J., and Hoffman, M.P. (2014). Hs3st3-modifiedheparan sulfate controls KIT+ progenitor expansion by regulating3-O-sulfotransferases. Dev Cell Jun
23;29(6):662-73. doi: 10.1016/j.devcel.2014.04.024.
- Patel, V.N, Hoffman, M.P. (2014). Salivarygland development: A template for regeneration. Semin Cell Dev Biol. S1084-9521(13)00130-4. doi:
- Lombaert, I.M.A., Abrams, S.R., Li, L,
Eswarakumar, V.P., Sethi, A.J., Witt, R.L., and Hoffman, M.P. (2013). CombinedKIT and FGFR2b signaling regulates epithelial progenitor expansion duringorganogenesis. Stem Cell Reports.
- Knox, S.M., Lombaert, I.M.A., Haddox, C.L.,
Abrams, S.R., Cotrim, A., Wilson, A.J., and Hoffman, MP. (2013).
Parasympathetic stimulation improves epithelial organ regeneration. Nat Commun, 2013 February 19, 4:1494.
Rebustini, I.T., Hayashi, T., Reynolds, A.D., Dillard, M.L., Carpenter, E.M., Hoffman, M.P. (2012). miR-200c regulates FGFR-dependent epithelialproliferation via Vldlr during submandibular gland branching morphogenesis. Development. Jan;139(1):191-202.
Knosp, W.M., Knox, S.M., and
Hoffman, M.P. (2011). Salivary gland organogenesis. WIRES Developmental Biology. Volume 1, Issue 1, pages 69–82,
January/February 2012. DOI: 10.1002/wdev.4.
- Knox, S. M., Lombaert, I. M. A., Reed, X., Gutkind, J. S, Vitale-Cross, L. and M. P. Hoffman. (2010). Parasympathetic innervation maintains epithelial progenitor cells during salivary organogenesis. Science, 329:1645-472.
- Rebustini, I.T., Myers, C., Lassiter, K.S., Surmak, A., Szabova, L., Holmbeck, K., Pedchenko, V., Hudson, B.G., and Hoffman, M.P. (2009). MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis. Dev Cell, Oct;17(4):482-93.
- Makarenkova*, H.P., Hoffman*, M.P., Beenken, A., Eliseenkova, A.V., Meech, R., Tsau, C., Patel, V.N., Lang, R.A., Mohammadi*, M. (2009) A molecular basis for FGF gradient formation and during branching morphogenesis. Science Signaling, 2 (88), ra55. DOI:10.1126/Scisignal.2000304. *These authors contributed equally to this work.
- Patel, V.N., Likar, K.M., Zisman-Rozen, S., Cowherd, S.N., Lassiter, K.S., Sher, I., Yates, E.A., Turnbull, J.E., Ron, D., and Hoffman, M.P. (2008). Specific Heparan Sulfate Structures Modulate FGF10-mediated Submandibular Gland Epithelial Morphogenesis and Differentiation. J Biol Chem 283, 9308-9317.
- Patel, V.N., Knox, S.M., Likar, K.M., Lathrop, C.A., Hossain, R., Eftekhari, S., Whitelock, J.M., Elkin, M., Vlodavsky, I., and Hoffman, M.P. (2007). Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis. Development 134, 4177-4186.
- Rebustini, I.T., Patel, V.N., Stewart, J.S., Layvey, A., Georges-Labouesse, E., Miner, J.H., and Hoffman, M.P. (2007). Laminin alpha5 is necessary for submandibular gland epithelial morphogenesis and influences FGFR expression through beta1 integrin signaling. Dev Biol 308, 15-29.
Complete CV and Publications (PDF File, 31KB)