BBS Faculty Member - Matthew Warman

Matthew Warman

Department of Genetics and Orthopaedic Surgery
Investigator, Howard Hughes Medican Institute
Director, Orthopaedic Research Laboratories


Boston Children's Hospital
Enders Building, Room 250
300 Longwood Ave
Boston, MA 02115
Tel: 617-919-2371
Fax: 617-730-0789
Email: matthew.warman@childrens.harvard.edu
Lab Members: 6 postdoctoral fellows, 2 students



My laboratory’s research focuses on the skeletal system. We employ a “bedside to bench to bedside” approach in order to delineate biologic pathways that are essential for skeletal health. Our research questions originate from patients with heritable disorders that affect bones and joints. We address these questions using genetic, cell biologic, biochemical, and model organism approaches. Our long-term goal is to understand the patterning, growth, and maintenance of the skeleton, since this will lead to improved care for patients affected by skeletal disease.

Examples of disorders we study and the questions they generate:

Acromesomelic dysplasia, type Maroteaux (AMDM), an autosomal recessive skeletal dysplasia that predominantly affects postnatal skeletal growth. We determined AMDM is caused by mutations in the gene encoding natriuretic peptide receptor B (NPR-B), which is a cell surface receptor expressed by growth plate chondrocytes. Questions we are working to answer include:
1) What pathways differentiate prenatal from postnatal skeletal growth?
2) How does NPR-B signaling regulate skeletal growth?
3) Can other components in this pathway be used as biomarkers for skeletal health?

Camptodactyly-Arthropathy-Coxa vara-Pericarditis syndrome (CACP), an autosomal recessive disorder that causes precocious joint failure. We determined CACP is caused by mutations in the gene encoding the secreted glycoprotein lubricin. Questions we are working to answer include:
1) What are the precise functions of lubricin in articulating joints?
2) Do acquired alterations in lubricin function increase one’s risk for common diseases such as osteoarthritis?

Osteoporosis-Pseudoglioma syndrome (OPPG), an autosomal recessive disorder that affects bone strength. We determined OPPG is caused by mutations in the gene encoding low-density lipoprotein receptor related protein 5 (LRP5), which is a cell surface receptor expressed by osteoblasts. Questions we are working to answer include:
1) What are the endogenous ligands and downstream signaling partners and targets for LRP5.
2) How does the LRP5 pathway regulate the function of bone forming cells?



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Jay, G.D., Torres, J.R., Rhee, D.K., Helminen, H.J., Hytinnen, M.M., Cha, C-J., Elsaid, K., Kim, K-S., Cui, Y., and Warman, M.L. (2007) The association between friction and wear in diarthrodal joints lacking lubricin. Arthritis & Rheumatism.

Smits, P., Bolton, A.D., Funari, V., Hong, M., Boyden, E.D., Lu, L., Manning, D.K., Dwyer, N.D., Moran, J.L., Prysak, M., Merriman, B., Nelson, S.F., Bonafe, L., Superti-Furga, A., Ikegawa, S., Krakow, D., Cohn, D.H., Kirchhausen, T., *
Warman, M.L., Beier, D.R. (2010) Lethal Skeletal Dysplasia in Mice and Humans Lacking the Golgin GMAP-210. New England Journal of Medicine. 362:206-216. (* corresponding author)

Bowen, M.E., Boyden, E.D., Holm, I.A., Campos-Xavier, B., Superti-Furga, A., Ikegawa, S., Cormier-Daire, V., Bovee, J.V., Pansuriya, T.C., de Sousa, S.B., Savarirayan, R., Andreucci, E., Vikkula, M., Garavelli, L., Pottinger, C., Ogino, T., Sakai, A., Regazoni, B.M., Wuyts, W., Sangiorgi, L., Pedrini, E., Zhu, M., Kozakewich, H.P., Kasser, J.R., Seidman, J.G., Kurek, K.C.,
Warman, M.L. (2011) Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome. PLoS Genetics 7:e1002050

Cui, Y., Niziolek, P.J., MacDonald, B.T., Zylstra, Alenina, N., Robinson, D.R., Zhong, Z., Matthes, S., Jacobsen, C.M., Conlon, R.A., Brommage, R., Liu, Q., Mseeh, F., Powell, D.R., Yang, Q.M., Zambrowicz, B., Gerrits, H., Gossen, J.A., He, X., Bader, M., Williams, B.O.,
*Warman, M.L., Robling, A.G. (2011) Lrp5 functions in bone to regulate bone mass. Nature Medicine. 17:684-691. (* corresponding author)



© 2013 by the President and Fellows of Harvard College