Our laboratory studies the molecular basis of the skeletal dysplasias, inherited human disorders that affect skeletal development, growth, and maintenance. Our goal is to provide a comprehensive understanding of the genes and gene products that participate in the development of the skeleton and that ultimately determine the shapes of the bones, the height an individual achieves, and the stability of the skeleton. A major step toward achieving our goals is genomic analysis in skeletal dysplasia families to identify the gene associated with each of the over 450 different skeletal dysplasias. For disorders in which the defective gene is known, a combination of mutation analysis and biosynthetic studies is used to understand the mechanisms by which the mutations arise, the inheritance pattern of each disorder, and the effect of each mutation of the synthesis, structure, and function of the encoded protein. These goals are augmented by studies in model organisms, particularly mice, that include mechanistic studies and the development of therapies to ameliorate or cure these disorders.
Csukasi F, Duran I, Zhang W, Martin JH, Barad M, Bamshad M, Weis MA, Eyre D, Krakow D, Cohn DH, "Dominant-negative SOX9 mutations in campomelic dysplasia", Human mutation (2019).
Balasubramanian K, Weis M, Eyre DR, Martin J, Ortiz-Sanchez J, Duran I, Vangala S, Wang J, Friedman RA, Krakow D, Cohn DH, "The ?2 chain of type IX collagen is essential for type IX collagen biosynthesis", American journal of medical genetics. Part A 179 (8): 1672-1677 (2019).
Burrage LC, Reynolds JJ, Baratang NV, Phillips JB, Wegner J, McFarquhar A, Higgs MR, Christiansen AE, Lanza DG, Seavitt JR, Jain M, Li X, Parry DA, Raman V, Chitayat D, Chinn IK, Bertuch AA, Karaviti L, Schlesinger AE, Earl D, Bamshad M, Savarirayan R, Doddapaneni H, Muzny D, Jhangiani SN, Eng CM, Gibbs RA, Bi W, Emrick L, Rosenfeld JA, Postlethwait J, Westerfield M, Dickinson ME, Beaudet AL, Ranza E, Huber C, Cormier-Daire V, Shen W, Mao R, Heaney JD, Orange JS, University of Washington Center for Mendelian Genomics., Undiagnosed Diseases Network., Bertola D, Yamamoto GL, Baratela WAR, Butler MG, Ali A, Adeli M, Cohn DH, Krakow D, Jackson AP, Lees M, Offiah AC, Carlston CM, Carey JC, Stewart GS, Bacino CA, Campeau PM, Lee B, "Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes", American journal of human genetics 104 (3): 422-438 (2019).
Hanson-Kahn A, Li B, Cohn DH, Nickerson DA, Bamshad MJ, University of Washington Center for Mendelian Genomics., Hudgins L, "Autosomal recessive Stickler syndrome resulting from a COL9A3 mutation", American journal of medical genetics. Part A 176 (12): 2887-2891 (2018).
Csukasi F, Duran I, Barad M, Barta T, Gudernova I, Trantirek L, Martin JH, Kuo CY, Woods J, Lee H, Cohn DH, Krejci P, Krakow D, "The PTH/PTHrP-SIK3 pathway affects skeletogenesis through altered mTOR signaling", Science translational medicine 10 (459): (2018).
Zhang W, Taylor SP, Ennis HA, Forlenza KN, Duran I, Li B, Sanchez JAO, Nevarez L, Nickerson DA, Bamshad M, University of Washington Center for Mendelian Genomics., Lachman RS, Krakow D, Cohn DH, "Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies", Human mutation 39 (1): 152-166 (2018).
Li B, Balasubramanian K, Krakow D, Cohn DH, "Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network", BMC genomics 18 (1): (2017).
Lee CS, Fu H, Baratang N, Rousseau J, Kumra H, Sutton VR, Niceta M, Ciolfi A, Yamamoto G, Bertola D, Marcelis CL, Lugtenberg D, Bartuli A, Kim C, Hoover-Fong J, Sobreira N, Pauli R, Bacino C, Krakow D, Parboosingh J, Yap P, Kariminejad A, McDonald MT, Aracena MI, Lausch E, Unger S, Superti-Furga A, Lu JT, Baylor-Hopkins Center for Mendelian Genomics., Cohn DH, Tartaglia M, Lee BH, Reinhardt DP, Campeau PM, "Mutations in Fibronectin Cause a Subtype of Spondylometaphyseal Dysplasia with "Corner Fractures"", American journal of human genetics 101 (5): 815-823 (2017).
Balasubramanian K, Li B, Krakow D, Nevarez L, Ho PJ, Ainsworth JA, Nickerson DA, Bamshad MJ, Immken L, Lachman RS, Cohn DH, "MED resulting from recessively inherited mutations in the gene encoding calcium-activated nucleotidase CANT1", American journal of medical genetics. Part A 173 (9): 2415-2421 (2017).
Badiner N, Taylor SP, Forlenza K, Lachman RS, University of Washington Center for Mendelian Genomics., Bamshad M, Nickerson D, Cohn DH, Krakow D, "Mutations in DYNC2H1, the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type", Clinical genetics 92 (2): 158-165 (2017).
Duran I, Martin JH, Weis MA, Krejci P, Konik P, Li B, Alanay Y, Lietman C, Lee B, Eyre D, Cohn DH, Krakow D, "A Chaperone Complex Formed by HSP47, FKBP65, and BiP Modulates Telopeptide Lysyl Hydroxylation of Type I Procollagen", Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32 (6): 1309-1319 (2017).
Duran I, Taylor SP, Zhang W, Martin J, Qureshi F, Jacques SM, Wallerstein R, Lachman RS, Nickerson DA, Bamshad M, Cohn DH, Krakow D, "Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia", Cilia 6: (2017).
Egunsola AT, Bae Y, Jiang MM, Liu DS, Chen-Evenson Y, Bertin T, Chen S, Lu JT, Nevarez L, Magal N, Raas-Rothschild A, Swindell EC, Cohn DH, Gibbs RA, Campeau PM, Shohat M, Lee BH, "Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia", The Journal of clinical investigation 127 (4): 1475-1484 (2017).
Zieba J, Zhang W, Chong JX, Forlenza KN, Martin JH, Heard K, Grange DK, Butler MG, Kleefstra T, Lachman RS, Nickerson D, Regnier M, Cohn DH, Bamshad M, Krakow D, "A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGF? signaling and cause autosomal dominant spondylocarpotarsal synostosis", Scientific reports 7: (2017).
Weinstein MM, Kang T, Lachman RS, Bamshad M, Nickerson DA, Krakow D, Cohn DH, "Somatic mosaicism for a lethal TRPV4 mutation results in non-lethal metatropic dysplasia", American journal of medical genetics. Part A 170 (12): 3298-3302 (2016).