Matt Warman, MD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2371


matthew.warman@childrens.harvard.edu

Matt Warman, MD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Professor, Genetics, Harvard Medical School
  • Harriet M. Peabody Professor of Orthopaedic surgery, Orthopaedic Surgery, Harvard Medical School
  • Professor, Genetics, Harvard Medical School
  • Director, Orthopaedic Research Laboratories, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Work in the Warman lab focuses on understanding biologic pathways that affect the patterning, growth, and maintenance of the skeletal system. Our long-term goal is to improve human skeletal health. We initially identified biologic pathways through the study of patients and their families who have well-defined heritable disorders affecting bones and joints; using this approach we determined that the Wnt signaling pathway is a key regulator of bone mass acquisition, the natriuretic peptide signaling pathway is an important effector of postnatal linear growth, and the glycoprotein lubricin is the principal boundary lubricant in articulating joints. We are currently employing biochemical, cellular, and model organism approaches to precisely delineate the roles of these pathways and proteins during growth and homeostasis. We have also extended our patient-oriented research to include families with unique syndromes and patients with sporadically occurring skeletal diseases. This has enabled us to identify a missense mutation in the nuclear pore protein, RANBP2, as a susceptibility locus for a novel, environmentally triggered, neurodegenerative disease, and several de novo microduplications or microdeletions as causes of sporadically occurring malformations that affect the patterning of the limbs and spine. These latter studies serve as an entrée toward our ultimate goal of being able to provide truly “personalized” genetic medicine to every patient with skeletal disease in whom a genetic contribution is suspected.

Publications

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  • Boscolo E, Coma S, Luks VL, Greene AK, Klagsbrun M, Warman ML, Bischoff J. AKT hyper-phosphorylation associated with PI3K mutations in lymphatic endothelial cells from a patient with lymphatic malformation. Angiogenesis 2015; 18:151-62. PubMed
  • Luks VL, Kamitaki N, Vivero MP, Uller W, Rab R, Bovée JV, Rialon KL, Guevara CJ, Alomari AI, Greene AK, Fishman SJ, Kozakewich HP, Maclellan RA, Mulliken JB, Rahbar R, Spencer SA, Trenor CC, Upton J, Zurakowski D, Perkins JA, Kirsh A, Bennett JT, Dobyns WB, Kurek KC, Warman ML, McCarroll SA, Murillo R. Lymphatic and Other Vascular Malformative/Overgrowth Disorders Are Caused by Somatic Mutations in PIK3CA. J Pediatr 2015; 166:1048-1054.e5. PubMed
  • Couto JA, Vivero MP, Kozakewich HP, Taghinia AH, Mulliken JB, Warman ML, Greene AK. A Somatic MAP3K3 Mutation Is Associated with Verrucous Venous Malformation. Am J Hum Genet 2015; 96:480-6. PubMed
  • Kozhemyakina E, Zhang M, Ionescu A, Ayturk UM, Ono N, Kobayashi A, Kronenberg H, Warman ML, Lassar AB. Identification of a Prg4-positive articular cartilage progenitor cell population. 2015. PubMed
  • Bowen ME, Ayturk UM, Kurek KC, Yang W, Warman ML. SHP2 Regulates Chondrocyte Terminal Differentiation, Growth Plate Architecture and Skeletal Cell Fates. PLoS Genet. 2014; 10:e1004364. PubMed
  • Maclellan RA, Luks VL, Vivero MP, Mulliken JB, Zurakowski D, Padwa BL, Warman ML, Greene AK, Kurek KC. PIK3CA activating mutations in facial infiltrating lipomatosis. Plast Reconstr Surg 2013; 133:12e-9e. PubMed
  • Allen JM, McGlinn E, Hill A, Warman ML. Autopodial development is selectively impaired by misexpression of chordin-like 1 in the chick limb. Dev Biol 2013; 381:159-69. PubMed
  • Hann S, Kvenvold L, Newby BN, Hong M, Warman ML. A Wisp3 Cre-knockin allele produces efficient recombination in spermatocytes during early prophase of meiosis I. PLoS ONE 2013; 8:e75116. PubMed
  • Kurek KC, Luks VL, Ayturk UM, Alomari AI, Fishman SJ, Spencer SA, Mulliken JB, Bowen ME, Yamamoto GL, Kozakewich HP, Warman ML. Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet 2012; 90:1108-15. PubMed
  • Nakamura Y, Yamamoto K, He X, Otsuki B, Kim Y, Murao H, Soeda T, Tsumaki N, Deng JM, Zhang Z, Behringer RR, Crombrugghe B, Postlethwait JH, Warman ML, Nakamura T, Akiyama H. Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25. Nat Commun 2011; 2:251. PubMed
  • Kohrs RT, Zhao C, Sun YL, Jay GD, Zhang L, Warman ML, An KN, Amadio PC. Tendon fascicle gliding in wild type, heterozygous, and lubricin knockout mice. J Orthop Res 2010. PubMed
  • Coles JM, Zhang L, Blum JJ, Warman ML, Jay GD, Guilak F, Zauscher S. Loss of cartilage structure, stiffness, and frictional properties in mice lacking Prg4. Arthritis Rheum 2010; 62:1666-74. PubMed
  • Fernando CA, Conrad PA, Bartels CF, Marques T, To M, Balow SA, Nakamura Y, Warman ML. Temporal and spatial expression of CCN genes in zebrafish. Dev Dyn 2010; 239:1755-67. PubMed
  • Kiener HP, Watts GF, Cui Y, Wright J, Thornhill TS, Sköld M, Behar SM, Niederreiter B, Lu J, Cernadas M, Coyle AJ, Sims GP, Smolen J, Warman ML, Brenner MB, Lee DM. Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture. Arthritis Rheum 2010; 62:742-52. PubMed
  • Smits P, Bolton AD, Funari V, Hong M, Boyden ED, Lu L, Manning DK, Dwyer ND, Moran JL, Prysak M, Merriman B, Nelson SF, Bonafé L, Superti-Furga A, Ikegawa S, Krakow D, Cohn DH, Kirchhausen T, Warman ML, Beier DR. Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210. N Engl J Med 2010; 362:206-16. PubMed
  • Nakamura Y, Cui Y, Fernando C, Kutz WE, Warman ML. Normal growth and development in mice over-expressing the CCN family member WISP3. J Cell Commun Signal 2009; 3:105-13. PubMed
  • Neilson DE, Adams MD, Orr CM, Schelling DK, Eiben RM, Kerr DS, Anderson J, Bassuk AG, Bye AM, Childs AM, Clarke A, Crow YJ, Di Rocco M, Dohna-Schwake C, Dueckers G, Fasano AE, Gika AD, Gionnis D, Gorman MP, Grattan-Smith PJ, Hackenberg A, Kuster A, Lentschig MG, Lopez-Laso E, Marco EJ, Mastroyianni S, Perrier J, Schmitt-Mechelke T, Servidei S, Skardoutsou A, Uldall P, van der Knaap MS, Goglin KC, Tefft DL, Aubin C, de Jager P, Hafler D, Warman ML. Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2. Am J Hum Genet 2009; 84:44-51. PubMed
  • Nakamura Y, Weidinger G, Liang JO, Aquilina-Beck A, Tamai K, Moon RT, Warman ML. The CCN family member Wisp3, mutant in progressive pseudorheumatoid dysplasia, modulates BMP and Wnt signaling. J Clin Invest 2007; 117:3075-86. PubMed
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