Marguerite Buzza, PhD

Buzza, M.S., Netzel-Arnett, S., Shea-Donohue, T., Zhao, A., Lin, C-Y., List, K., Szabo, R., Fasano, A., Bugge, T.H. and Antalis, T.A. (2010).  The membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine. Proc Natl Acad Sci U S A. Mar 2;107(9):4200-5 *a commentary on this manuscript was published in the "Highlights from the Literature" section of the journal Physiology, 25:128-131, 2010.  PMCID: PMC2840089

Tripathi, A., Lammers, K. M., Goldbulm, S., Shea-Donohue, T., Netzel-Arnett, S., Buzza,   M.S., Antalis, T.M., Vogel, S.N, Zhao, A., Yang, S., Arrietta, M.C., Meddings, J.B. and Fasano, A. (2009). Identification of human Zonulin, a physiological modulator of tight junctions, as Pre-haptoglobin-2. Proc Natl Acad Sci U S A. 106(39):16799-804.  PMCID: PMC2744629

Tonnetti, L., Netzel-Arnett, S., Darnell, G.A., Hayes, T., Buzza, M.S., Anglin, I.E., Suhrbier, A. and Antalis, T.M. (2008). SerpinB2 protection of retinoblastoma protein from calpain enhances tumor cell survival. Cancer Res. 68(14):5648-57.  PMCID: PMC2561898

Buzza, M.S., Dyson, J.M., Choi, H., Gardiner E.E., Andrews, R.K., Kaiserman, D., Mitchell, C.A., Berndt, M.C., Dong, J.F. and Bird, P.I. (2008). Antihemostatic activityof human granzyme B mediated by cleavage of von Willebrand factor. J Biol Chem. 283(33):22498-504.

Buzza, M.S. and Bird P.I. (2006). Extracellular granzymes: current perspectives. Biol. Chem. 387(7):827-37.

Buzza, M.S., Hosking P. and Bird, P.I. (2006). The granzyme B inhibitor, PI-9, is differentially expressed during placental development and up-regulated in hydatidiform moles. Placenta. 27(1):62-9.

Buzza, M.S., Zamurs, L., Sun, J., Bird, C.H., Smith, A I., Trapani, J.A., Froelich, C.J., Nice, E.C. and Bird P.I. (2005). Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronectin and laminin. J Biol Chem. 280(25):23549-58.

Law R. H., Irving, J.A., Buckle, A.M., Ruzyla K., Buzza, M., Bushtannyk-Puhalovich T.A., Beddoe, T. C., Nguyen K., Worrall, D.M., Bottomley, S.P, Bird, P.I., Rossjohn J., Whisstock, J.C. (2005). The high resolution crystal structure of the human tumor suppressor maspin reveals a novel conformational switch in the G-helix. J Biol Chem. 280(23): 22356-64.

Hirst C.E., Buzza, M.S., Bird, C.H., Warren, H.S., Cameron, P.U., Zhang, M., Ashton-Rickardt, P.G. and Bird, P.I. (2003). The intracellular granzyme B inhibitor PI-9, is up-regulated during accessory cell maturation and effector cell degranulation, and its overexpression enhances CTL potency. J Immunol. 170(2): 805-15

*Buzza, M.S., *Hirst, C.E., Sutton, V.R., Trapani, J.A., Loveland, K.L. and Bird, P.I. (2001). Perforin-independent expression of granzyme B and proteinase inhibitor 9 in human testis and placenta suggests a role for granzyme B-mediated proteolysis in reproduction.  Mol Hum Reprod. 7(12): 1133-42. *Equal first author with Hirst, as noted on title page.

Bird, C.H., Blink, E.J., Hirst, C.E., Buzza, M.S., Steele, P.M., Sun, J., Jans, D.A. and Bird P.I. (2001). Nucleocytoplasmic distribution of the ovalbumin serpin PI-9 requires a non-conventional nuclear import pathway and the export factor Crm1. Mol Cell Biol. 21(16): 5396-407. PMCID: PMC87262

Buzza, M.S., Hirst, C.E., Bird, C.H., Hosking, P., McKendrick, J. and Bird P.I. (2001). The granzyme B inhibitor, PI-9, is present in endothelial cells and mesothelial cells, suggesting it protects bystander cells during immune responses. Cell Immunol. 210(1): 21-9.

Sun, J., Bird, C.H., Buzza, M.S., McKee, K.E., Whisstock, J.C. and Bird, P.I. (1999). Expression and purification of recombinant human granzyme B from Pichia pastoris. Biochem Biophys Res Commun. 216(2):251-5.

Martin, E.W., Buzza, M.S., Driesbaugh, K.H., Liu, S., Fortenberry, Y.M., Leppla, S.H., Antalis, T.M. (2015) Targeting the membrane-anchored serine protease testisin with a novel engineered anthrax toxin prodrug to kill tumor cells and reduce tumor burden. Oncotarget. 2015 Sep 15. PMID: 26392335

Publications - Book chapters
Antalis T.M., and Buzza M.S. Extracellular: Plasma Membrane Proteases – Serine Proteases. R.A. Bradshaw and P.D. Stahl (Editors-in-Chief), In: Encyclopedia of Cell Biology, Vol 1, Waltham, MA: Academic Press, 2016, pp.650-660.

Matriptase is one of a unique group of serine proteases that is directly tethered to the surface of epithelial cells that line the intestinal tract. We have determined that Matriptase, which is localized to adherens junctions in polarized intestinal epithelial cells, is required for closure of the paracellular pathway through an atypical PKC-mediated signaling pathway that regulates tight junction formation. Recently my research has involved understanding the contribution of Matriptase-mediated barrier formation in Inflammatory Bowel Diseases (IBD). We found that Matriptase expression is markedly down-regulated in human IBD, where increased intestinal permeability is thought to be causally linked to disease pathogenesis. Furthermore, using a murine hypomorph model of Matriptase deficiency we showed that that loss of Matriptase leads to increased disease susceptibility and failure to recover from a murine model of experimental colitis. I have recently discovered that Matriptase requires proteolytic activation by another upstream membrane-anchored protease, called Prostasin, before it can induce intestinal barrier formation, suggesting the existence of a novel proteolytic pathway in this tissue. My current research focuses on the mechanisms by which Matriptase function is regulated, and in the identification of the downstream molecules which are regulated by Matriptase to induce intestinal barrier function.

FASEB SRC Poster Award for outstanding poster presentation at the FASEB SRC Proteases in Hemostasis & Vascular Biology conference, 2015, Keystone, CO.

Service activities

• Co-organizer of the Center for Vascular and Inflammatory Diseases (CVID) Seminar Series, University of Maryland
• Ad hoc reviewer for Journal of Biological Chemistry
• Ad hoc reviewer for American Journal of Physiology
• Ad hoc reviewer for Journal of Investigative Dermatology
• Ad hoc reviewer for Immunology and Cell Biology
• Ad hoc reviewer for PlosOne

Teaching activities

• Daily laboratory supervision and mentoring of doctoral candidates:
  • Gregory Conway
  • Tierra Johnson
  • Raymond Peroutka
  • Nisha Pawar
• Associate Member of the Graduate Faculty of the University of Maryland Graduate School, Dec 2014-present
• Thesis advisory committee member for Gregory Conway and Raymond Peroutka, Molecular Medicine Program, GPILS, Dec 2015- present