William A. Frazier, Ph.D.

Professor

Biochemistry and Molecular Biophysics

Lab Website
Graduate Programs (DBBS)
Publications (PubMed / NIH)

Office: 1914A South Building

Email: frazier@wustl.edu

 

Research

A Nobel Prize was awarded for the discovery of the physiological role of nitric oxide and NO was named the 1992 “Molecule of the Year” by Science magazine. The Frazier lab discovered that CD47 is a receptor for thrombospondin-1 and that TSP1 ligation of CD47 negates the beneficial effects of NO signaling thereby exacerbating all cardiovascular diseases. We are now studying the molecular details of the TSP1-CD47 binding interaction, the mechanism of CD47 inhibition of NO signaling and discovering new phenotypes of CD47-null mice.

Select Publications

Xiao Z., Banan B., Xu M., Jia J., Manning P.T., Hiebsch R.R., Gunasekaran M., Upadhya G.A., Frazier W.A., Mohanakumar T., Lin Y., & Chapman W.C. (2016). “Attenuation of Ischemia-Reperfusion Injury and Improvement of Survival in Recipients of Steatotic Rat Livers Using CD47 Monoclonal Antibody.” Transplantation. 2016 Jul;100(7):1480-9. doi: 10.1097/TP.0000000000001186. (Abstract)

Liu X., Pu Y., Cron K., Deng L., Kline J., Frazier W.A., Xu H., Peng H., Fu Y.X., & Xu M.M. (2015). “CD47 blockade triggers T cell-mediated destruction of immunogenic tumors.” Nat Med. 2015 Oct;21(10):1209-15. doi: 10.1038/nm.3931. Epub 2015 Aug 31. (Abstract)

Liu K.E. & Frazier W.A. (2015). “Phosphorylation of the BNIP3 C-Terminus Inhibits Mitochondrial Damage and Cell Death without Blocking Autophagy.” PLoS One. 2015 Jun 23;10(6):e0129667. doi: 10.1371/journal.pone.0129667. eCollection 2015. (Abstract)

Xiao Z.Y., Chung H., Banan B., Manning P.T., Ott K.C., Lin S., Capoccia B.J., Subramanian V., Hiebsch R.R., Upadhya G., Mohanakumar T., Frazier W.A., Lin Y., & Chapman W.C. (2015). “Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma.” Cancer Lett. 2015 May 1;360(2):302-9. doi: 10.1016/j.canlet.2015.02.036. Epub 2015 Feb 23. (Abstract)

Amend S.R., Uluckan O., Hurchla M., Leib D., Novack D.V., Silva M., Frazier W., & Weilbaecher K.N. (2015). “Thrombospondin-1 regulates bone homeostasis through effects on bone matrix integrity and nitric oxide signaling in osteoclasts.” J Bone Miner Res. 2015 Jan;30(1):106-15. doi: 10.1002/jbmr.2308. (Abstract)

Xiao Z.Y., Banan B., Jia J., Manning P.T., Hiebsch R.R., Gunasekaran M., Upadhya G., Frazier W.A., Mohanakumar T., & Chapman W.C. (2015). “CD47 blockade reduces ischemia/reperfusion injury and improves survival in a rat liver transplantation model.” Liver Transpl. 2015 Apr;21(4):468-477. doi: 10.1002/lt.24059. Epub 2015 Jan 29. (Abstract)

Lin Y., Manning P.T., Jia J., Gaut J.P., Xiao Z., Capoccia B.J., Chen C.C., Hiebsch R.R., Upadhya G., Mohanakumar T., Frazier W.A., & Chapman W.C. (2014). “CD47 blockade reduces ischemia-reperfusion injury and improves outcomes in a rat kidney transplant model.” Transplantation. 2014 Aug 27;98(4):394-401. doi: 10.1097/TP.0000000000000252. (Abstract)

Zheleznyak A., Ikotun O.F., Dimitry J., Frazier W.A., & Lapi S.E. (2013). “Imaging of CD47 expression in xenograft and allograft tumor models.” Mol Imaging. 2013 Nov-Dec;12(8). doi: 10.2310/7290.2013.00069. (Abstract)

Azcutia V., Routledge M., Williams M.R., Newton G., Frazier W.A., Manica A., Croce K.J., Parkos C.A., Schmider A.B., Turman M.V., Soberman R.J., & Luscinskas F.W. (2013). “CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions.” Mol Biol Cell. 2013 Nov;24(21):3358-68. doi: 10.1091/mbc.E13-01-0063. Epub 2013 Sep 4. (Abstract)

Soto-Pantoja D.R., Miller T.W., Frazier W.A., & Roberts D.D. (2012). “Inhibitory signaling through signal regulatory protein-α is not sufficient to explain the antitumor activities of CD47 antibodies.” Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):E2842; author reply E2844-5. doi: 10.1073/pnas.1205441109. Epub 2012 Aug 24. (Abstract)

Frazier E.P., Isenberg J.S., Shiva S., Zhao L., Schlesinger P., Dimitry J., Abu-Asab M.S., Tsokoa M., Roberts D.D., & Frazier W.A. (2011). “Age-dependent regulation of skeletal muscle mitochondria by the thrombospondin-1 receptor CD47.” Matrix Biol. 2011 Mar;30(2):154-61. doi: 10.1016/j.matbio.2010.12.004. Epub 2011 Jan 20. (Abstract)

Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A., Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A., Khoury J.E., Golenbock D.T., & Moore K.J. (2010). “CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.” Nat Immunol. 2010 Feb;11(2):155-61. doi: 10.1038/ni.1836. Epub 2009 Dec 27. (Abstract)

Uluckan O., Becker S.N., Deng H., Zou W., Prior J.L., Piwnica-Worms D., Frazier W.A., & Weilbaecher K.N. (2009). “CD47 regulates bone mass and tumor metastasis to bone.” Cancer Res. 2009 Apr 1;69(7):3196-204. doi: 10.1158/0008-5472.CAN-08-3358. Epub 2009 Mar 10. (Abstract)

Isenberg J.S., Ridnour L.A., Dimitry J., Frazier W.A., Wink D.A., & Roberts D.D. (2006). “CD47 is necessary for inhibition of nitric oxide-stimulated vascular cell responses by thrombospondin-1.” J Biol Chem. 2006 Sep 8;281(36):26069-80. Epub 2006 Jul 11. (Abstract)

Hagnerud S., Manna P.P., Cella M., Stenberg A., Frazier W.A., Colonna M., & Oldenborg P.A. (2006). “Deficit of CD47 results in a defect of marginal zone dendritic cells, blunted immune response to particulate antigen and impairment of skin dendritic cell migration.” J Immunol. 2006 May 15;176(10):5772-8. (Abstract)