David E. Birk, PhD

Where You Are:
David E. Birk, PhD

Office  (813) 974-8598

Education And Training
  • PhD, Wayne State University, 1981 - Anatomy

My research interests involve the cell and developmental biology of extracellular matrix. Our major focus is on acquisition of tissue-specific structure and function. These studies address fundamental questions regarding regulation of assembly and are relevant to connective tissues in general. We focus primarily on regulatory interactions involving matrix macromolecules as well as the influence of the fibroblast. We utilize mouse models and extend the work to human tissues as appropriate. While our focus is on the elucidation of the steps involved in tissue morphogenesis and growth, the questions also address repair/regeneration as well as dysfunctional regulation in connective tissue disorders. This focus also complements studies of abnormal growth, cell migration

and cell-matrix interactions in cancer biology and angiogenesis. We are using transgenic models provided by other investigators or created in my laboratory. We

then integrate biochemical, immunochemical, molecular, biomechanical and ultrastructural approaches in our analyses. In addition, my laboratory has a major interest in biological imaging. Our experience with transmission electron microscopy and our ultrastructural analyses are considered laboratory strengths.

  • Chiquet M, Birk DE, Bönnemann CG, Koch M. Collagen XII: Protecting bone and muscle integrity by organizing collagen fibrils. Int J Biochem Cell B. 2014 Aug;53:51-54. Pubmedid: 24801612.
  • Mienaltowski MJ, Adams SM, Birk DE. Tendon proper- and peritenon-derived progenitor cells have unique tenogenic properties. Stem Cell Res Ther. 2014 Jul;5(4):86. Pubmedid: 25005797.
  • Zou Y, Zwolanek D, Izu Y, Gandhy S, Schreiber G, Brockmann K, Devoto M, Tian Z, Hu Y, Veit G, Meier M, Stetefeld J, Hicks D, Straub V, Voermans NC, Birk DE, Barton ER, Koch M, Bönnemann CG. Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice. Hum Mol Genet. 2014 May;23(9):2339-2352. Pubmedid: 24334604. Pmcid: PMC3976332.
  • Pan TC, Zhang RZ, Arita M, Bogdanovich S, Adams SM, Gara SK, Wagener R, Khurana TS, Birk DE, Chu ML. A mouse model for dominant collagen VI disorders: heterozygous deletion of Col6a3 Exon 16. J Biol Chem. 2014 Apr;289(15):10293-10307. Pubmedid: 24563484. Pmcid: PMC4036154.
  • Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Kumar A, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ. The injury response of aged tendons in the absence of biglycan and decorin. Matrix Biol. 2014 Apr;35:232-238. Pubmedid: 24157578. Pmcid: PMC3994176.
  • Chen S, Young MF, Chakravarti S, Birk DE. Interclass small leucine-rich repeat proteoglycan interactions regulate collagen fibrillogenesis and corneal stromal assembly. Matrix Biol. 2014 Apr;35:103-111. Pubmedid: 24447998.
  • Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Satchell L, Kumar A, Pathmanathan L, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ. The Tendon Injury Response is Influenced by Decorin and Biglycan. Ann Biomed Eng. 2014 Mar;42(3):619-630. Pubmedid: 24072490.
  • Smith SM, Zhang G, Birk DE. Collagen V localizes to pericellular sites during tendon collagen fibrillogenesis. Matrix Biol. 2014 Jan;33:47-53. Pubmedid: 23954412. Pmcid: PMC3925462.
  • Mienaltowski MJ, Birk DE. Mouse models in tendon and ligament research. Adv Exp Med Biol. 2014;802:201-230. Pubmedid: 24443029.
  • Mienaltowski MJ, Birk DE. Structure, physiology, and biochemistry of collagens. Adv Exp Med Biol. 2014;802:5-29. Pubmedid: 24443018.
  • Dourte LM, Pathmanathan L, Mienaltowski MJ, Jawad AF, Birk DE, Soslowsky LJ. Mechanical, compositional, and structural properties of the mouse patellar tendon with changes in biglycan gene expression. J Orthop Res. 2013 Sep;31(9):1430-1437. Pubmedid: 23592048. Pmcid: PMC3801205.
  • Buckley MR, Huffman GR, Iozzo RV, Birk DE, Soslowsky LJ. The location-specific role of proteoglycans in the flexor carpi ulnaris tendon. Connect Tissue Res. 2013 Aug;54(6):367-373. Pubmedid: 23941206.
  • Chen S, Sun M, Iozzo RV, Kao WW, Birk DE. Intracellularly-retained decorin lacking the C-terminal ear repeat causes ER stress: a cell-based etiological mechanism for congenital stromal corneal dystrophy. Am J Pathol. 2013 Jul;183(1):247-256. Pubmedid: 23685109. Pmcid: PMC3702738.
  • Connizzo BK, Sarver JJ, Iozzo RV, Birk DE, Soslowsky L. Erratum: "Effect of Age and Proteoglycan Deficiency on Collagen Fiber Re-Alignment and Mechanical Properties in Mouse Supraspinatus Tendon, "[Journal of Biomechanical Engineering, 135(2), 021019]. J Biomech Eng. 2013 Jun. Pubmedid: 23774907.
  • Chen S, Birk DE. The regulatory roles of small leucine-rich proteoglycans in extracellular matrix assembly. FEBS J. 2013 May;280(10):2120-2137. Pubmedid: 23331954. Pmcid: PMC3651807.
  • Hemmavanh C, Koch M, Birk DE, Espana EM. Abnormal corneal endothelial maturation in collagen XII and XIV null mice. Invest Ophthalmol Vis Sci. 2013 May;54(5):3297-3308. Pubmedid: 23599329. Pmcid: PMC3648227.
  • Pan TC, Zhang RZ, Markova D, Arita M, Zhang Y, Bogdanovich S, Khurana TS, Bonnemann CG, Birk DE, Chu ML. COL6A3 protein deficiency in mice leads to muscle and tendon defects similar to human collagen VI congenital muscular dystrophy. J Biol Chem. 2013 May;288(20):14320-14331. Pubmedid: 23564457. Pmcid: PMC3656288.
  • Buckley MR, Dunkman AA, Reuther KE, Kumar A, Pathmanathan L, Beason DP, Birk DE, Soslowsky LJ. Validation of an empirical damage model for aging and in vivo injury of the murine patellar tendon. J Biomech Eng. 2013 Apr;135(4):41005. Pubmedid: 24231900.
  • Mienaltowski MJ, Adams SM, Birk DE. Regional differences in stem cell/progenitor cell populations from the mouse achilles tendon. Tissue Eng Part A. 2013 Jan;19(1-2):199-210. Pubmedid: 22871316. Pmcid: PMC3530943.
  • Dunkman AA, Buckley MR, Mienaltowski MJ, Adams SM, Thomas SJ, Satchell L, Kumar A, Pathmanathan L, Beason DP, Iozzo RV, Birk DE, Soslowsky LJ. Decorin expression is important for age-related changes in tendon structure and mechanical properties. Matrix Biol. 2013 Jan;32(1):3-13. Pubmedid: 23178232. Pmcid: PMC3615887.
  • Tao G, Levay AK, Peacock JD, Huk DJ, Both SN, Purcell NH, Pinto JR, Galantowicz ML, Koch M, Lucchesi PA, Birk DE, Lincoln J. Collagen XIV is important for growth and structural integrity of the myocardium. J Mol Cell Cardiol. 2012 Nov;53(5):626-638. Pubmedid: 22906538. Pmcid: PMC3472103.
  • Smith SM, Thomas CE, Birk DE. Pericellular proteins of the developing mouse tendon: a proteomic analysis. Connect Tissue Res. 2012 Sep;53(1):2-13. Pubmedid: 21851252. Pmcid: PMC3771084.
  • Smith SM, Birk DE. Focus on molecules: collagens V and XI. Exp Eye Res. 2012 May;98:105-106. Pubmedid: 20705069. Pmcid: PMC2996481.
  • Ansorge HL, Adams S, Jawad AF, Birk DE, Soslowsky LJ. Mechanical property changes during neonatal development and healing using a multiple regression model. J Biomech. 2012 Apr;45(7):1288-1292. Pubmedid: 22381737. Pmcid: PMC3327817.
  • Dourte LM, Pathmanathan L, Jawad AF, Iozzo RV, Mienaltowski MJ, Birk DE, Soslowsky LJ. Influence of decorin on the mechanical, compositional, and structural properties of the mouse patellar tendon. J Biomech Eng. 2012 Mar;134(3):031005. Pubmedid: 22482685. Pmcid: PMC3705828.
  • Ansorge HL, Hsu JE, Edelstein L, Adams S, Birk DE, Soslowsky LJ. Recapitulation of the Achilles tendon mechanical properties during neonatal development: a study of differential healing during two stages of development in a mouse model. J Orthop Res. 2012 Mar;30(3):448-456. Pubmedid: 22267191. Pmcid: PMC3265027.
  • Chervoneva I, Zhan T, Iglewicz B, Hauck WW, Birk DE. Two-stage hierarchical modeling for analysis of subpopulations in conditional distributions. J Appl Stat. 2012;39(2):445-460. Pubmedid: 22523443.
  • Sun M, Chen S, Adams SM, Florer JB, Liu H, Kao WW, Wenstrup RJ, Birk DE. Collagen V is a dominant regulator of collagen fibrillogenesis: dysfunctional regulation of structure and function in a corneal-stroma-specific Col5a1-null mouse model. J Cell Sci. 2011 Dec;124(Pt 23):4096-4105. Pubmedid: 22159420. Pmcid: PMC3244988.
  • Chen S, Sun M, Meng X, Iozzo RV, Kao WW, Birk DE. Pathophysiological mechanisms of autosomal dominant congenital stromal corneal dystrophy: C-terminal-truncated decorin results in abnormal matrix assembly and altered expression of small leucine-rich proteoglycans. Am J Pathol. 2011 Nov;179(5):2409-2419. Pubmedid: 21893019. Pmcid: PMC3204084.
  • Ansorge HL, Adams S, Birk DE, Soslowsky LJ. Mechanical, compositional, and structural properties of the post-natal mouse Achilles tendon. Ann Biomed Eng. 2011 Jul;39(7):1904-1913. Pubmedid: 21431455. Pmcid: PMC3341172.
  • Izu Y, Sun M, Zwolanek D, Veit G, Williams V, Cha B, Jepsen KJ, Koch M, Birk DE. Type XII collagen regulates osteoblast polarity and communication during bone formation. J Cell Biol. 2011 Jun;193(6):1115-1130. Pubmedid: 21670218. Pmcid: PMC3115787.
  • Chen S, Birk DE. Focus on molecules: decorin. Exp Eye Res. 2011 Jun;92(6):444-445. Pubmedid: 20493188. Pmcid: PMC2957536.
  • Wenstrup RJ, Smith SM, Florer JB, Zhang G, Beason DP, Seegmiller RE, Soslowsky LJ, Birk DE. Regulation of collagen fibril nucleation and initial fibril assembly involves coordinate interactions with collagens V and XI in developing tendon. J Biol Chem. 2011 Jun;286(23):20455-20465. Pubmedid: 21467034. Pmcid: PMC3121453.
  • Izu Y, Ansorge HL, Zhang G, Soslowsky LJ, Bonaldo P, Chu ML, Birk DE. Dysfunctional tendon collagen fibrillogenesis in collagen VI null mice. Matrix Biol. 2011 Jan;30(1):53-61. Pubmedid: 20951202. Pmcid: PMC3778658.
  • Hassell JR, Birk DE. The molecular basis of corneal transparency. Exp Eye Res. 2010 Sep;91(3):326-335. Pubmedid: 20599432. Pmcid: PMC3726544.
  • Etheredge L, Kane BP, Valkov N, Adams S, Birk DE, Hassell JR. Enhanced cell accumulation and collagen processing by keratocytes cultured under agarose and in media containing IGF-I, TGF-β or PDGF. Matrix Biol. 2010 Jul;29(6):519-524. Pubmedid: 20580823. Pmcid: PMC2939170.
  • Chen S, Oldberg A, Chakravarti S, Birk DE. Fibromodulin regulates collagen fibrillogenesis during peripheral corneal development. Dev Dyn. 2010 Mar;239(3):844-854. Pubmedid: 20108350. Pmcid: PMC2965449.
  • Du Y, Carlson EC, Funderburgh ML, Birk DE, Pearlman E, Guo N, Kao WW, Funderburgh JL. Stem cell therapy restores transparency to defective murine corneas. Stem Cells. 2009 Jul;27(7):1635-1642. Pubmedid: 19544455. Pmcid: PMC2877374.
  • Ansorge HL, Meng X, Zhang G, Veit G, Sun M, Klement JF, Beason DP, Soslowsky LJ, Koch M, Birk DE. Type XIV Collagen Regulates Fibrillogenesis: PREMATURE COLLAGEN FIBRIL GROWTH AND TISSUE DYSFUNCTION IN NULL MICE. J Biol Chem. 2009 Mar;284(13):8427-8438. Pubmedid: 19136672. Pmcid: PMC2659201.
  • Hassell JR, Kane BP, Etheredge LT, Valkov N, Birk DE. Increased stromal extracellular matrix synthesis and assembly by insulin activated bovine keratocytes cultured under agarose. Exp Eye Res. 2009 Jan;87(6):604-611. Pubmedid: 18938157. Pmcid: PMC3771087.
  • Du Y, Sundarraj N, Funderburgh ML, Harvey SA, Birk DE, Funderburgh JL. Secretion and organization of a cornea-like tissue in vitro by stem cells from human corneal stroma. Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5038-5045. Pubmedid: 17962455. Pmcid: PMC2874676.
  • Wenstrup RJ, Florer JB, Davidson JM, Phillips CL, Pfeiffer BJ, Menezes DW, Chervoneva I, Birk DE. Murine model of the Ehlers-Danlos syndrome. col5a1 haploinsufficiency disrupts collagen fibril assembly at multiple stages. J Biol Chem. 2006 May;281(18):12888-12895. Pubmedid: 16492673.
  • Christner PJ, Gentiletti J, Peters J, Ball ST, Yamauchi M, Atsawasuwan P, Beason DP, Soslowsky LJ, Birk DE. Collagen dysregulation in the dermis of the Sagg/+ mouse: a loose skin model. J Invest Dermatol. 2006 Mar;126(3):595-602. Pubmedid: 16424879.
  • Carlson EC, Liu CY, Chikama T, Hayashi Y, Kao CW, Birk DE, Funderburgh JL, Jester JV, Kao WW. Keratocan, a cornea-specific keratan sulfate proteoglycan, is regulated by lumican. J Biol Chem. 2005 Jul;280(27):25541-25547. Pubmedid: 15849191. Pmcid: PMC2874675.
  • Colombo M, Brittingham RJ, Klement JF, Majsterek I, Birk DE, Uitto J, Fertala A. Procollagen VII self-assembly depends on site-specific interactions and is promoted by cleavage of the NC2 domain with procollagen C-proteinase. Biochemistry-Us. 2003 Oct;42(39):11434-11442. Pubmedid: 14516194.
  • Cai CX, Birk DE, Linsenmayer TF. Nuclear ferritin protects DNA from UV damage in corneal epithelial cells. Mol Biol Cell. 1998 May;9(5):1037-1051. Pubmedid: 9571238. Pmcid: PMC25328.
  • Liaw L, Birk DE, Ballas CB, Whitsitt JS, Davidson JM, Hogan BL. Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest. 1998 Apr;101(7):1468-1478. Pubmedid: 9525990. Pmcid: PMC508725.
  • Nurminskaya MV, Birk DE. Differential expression of fibromodulin mRNA associated with tendon fibril growth: isolation and characterization of a chicken fibromodulin cDNA. Biochem J. 1996 Aug;317 ( Pt 3):785-789. Pubmedid: 8760363. Pmcid: PMC1217553.
  • Birk DE, Zycband E. Assembly of the tendon extracellular matrix during development. J Anat. 1994 Jun;184 ( Pt 3):457-463. Pubmedid: 7928635. Pmcid: PMC1259954.
  • Linsenmayer TF, Gibney E, Igoe F, Gordon MK, Fitch JM, Fessler LI, Birk DE. Type V collagen: molecular structure and fibrillar organization of the chicken alpha 1(V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis. J Cell Biol. 1993 Jun;121(5):1181-1189. Pubmedid: 8501123. Pmcid: PMC2119697.
  • Birk DE, Zycband EI, Winkelmann DA, Trelstad RL. Collagen fibrillogenesis in situ: fibril segments are intermediates in matrix assembly. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4549-4553. Pubmedid: 2734306. Pmcid: PMC287308.
  • Birk DE, Fitch JM, Babiarz JP, Linsenmayer TF. Collagen type I and type V are present in the same fibril in the avian corneal stroma. J Cell Biol. 1988 Mar;106(3):999-1008. Pubmedid: 3346334. Pmcid: PMC2115105.
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