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Alexander Awgulewitsch

Title
InstitutionMedical University of South Carolina
DepartmentRheumatology
AddressP.O. Box MSC 637
CRI 606
Children's Research Inst. - 173 Ashley Ave.
Phone843-792-8946
Fax843-792-7121
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    Alexander Awgulewitsch is Associate Professor of Medicine and Director of the MUSC Transgenic Mouse Core Facility. He received a Ph.D. (Dr. rer. nat.) degree at the Institute of Genetics, University of Düsseldorf, Germany, in 1984. He did postdoctoral studies in mammalian developmental genetics with the late Dr. Frank Ruddle at Yale University until 1988. That same year he was appointed Assistant Professor at the Department of Biochemistry at MUSC. He was promoted to Associate Professor in 1992 before joining the faculty of the Department of Medicine in 1993.

    A primary interest of Dr. Awgulewitsch is in studying the roles of Hox transcriptional regulators in development and disease. These genes are critical for specifying positional identities during embryonic patterning. This involves phylogenetically conserved transcriptional control mechanisms for directing spatially restricted Hox expression patterns as illustrated by the functional conservation of Hox transcriptional enhancers from the fruit fly in transgenic mice (Awgulewitsch & Jacobs 1992; Papenbrock et al. 1998).

    Apparently, these positional identities are retained to some degree in the adult organism where Hox genes are believed to control tissue homeostasis by regulating local cell differentiation events. To this end, a current focus of the lab is on determining the role of certain Hox genes in the adult cardiovascular system where they exhibit topographic expression patterns in vascular smooth muscle and endothelial cells (Pruitt et al. 2008). Our experimental approach for validating this paradigm of a vascular topographic Hox code includes disrupting this code in mice. Using a novel integrated Tet-regulatory transgenic system, vascular expression patterns of topographically restricted Hox genes are re-directed in an inducible manner (Pruett et al. 2012). The resulting region-specific structural and molecular changes in the vessel wall provide important insight into Hox-dependent genetic pathways underlying various vascular disorders that exhibit topographic patterns (e.g. atherosclerosis and aortic aneurysms) (Awgulewitsch & Majesky 2013). Furthermore, this work yields insight into Hox-regulated angiogenic pathways during wound healing and tumor growth.

    A second system for gaining insight into Hox-regulated pathways is hair follicle biology with Hoxc13 being used as a paradigm. Hoxc13 is essential for proper differentiation of keratinocytes of different lineages. Using Hoxc13 transgenic mice, we have identified numerous Hoxc13-regulated target genes of diverse functional categories, including keratins, desmosomal cadherins, and transcription factors (e.g. Tkatchenko et al. 2001 Pruett et al. 2004; Potter et al. 2006, 2011). This ongoing work involves a long-standing collaboration with Dr. Sundberg from The Jackson Laboratory in Maine.
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    animal models, genetics

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Toomer KA, Yu M, Fulmer D, Guo L, Moore KS, Moore R, Drayton KD, Glover J, Peterson N, Ramos-Ortiz S, Drohan A, Catching BJ, Stairley R, Wessels A, Lipschutz JH, Delling FN, Jeunemaitre X, Dina C, Collins RL, Brand H, Talkowski ME, Del Monte F, Mukherjee R, Awgulewitsch A, Body S, Hardiman G, Hazard ES, da Silveira WA, Wang B, Leyne M, Durst R, Markwald RR, Le Scouarnec S, Hagege A, Le Tourneau T, Kohl P, Rog-Zielinska EA, Ellinor PT, Levine RA, Milan DJ, Schott JJ, Bouatia-Naji N, Slaugenhaupt SA, Norris RA. Primary cilia defects causing mitral valve prolapse. Sci Transl Med. 2019 05 22; 11(493). PMID: 31118289.
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    2. Ding L, Shunkwiler LB, Harper NW, Zhao Y, Hinohara K, Huh SJ, Ekram MB, Guz J, Kern MJ, Awgulewitsch A, Shull JD, Smits BMG, Polyak K. Deletion of Cdkn1b in ACI rats leads to increased proliferation and pregnancy-associated changes in the mammary gland due to perturbed systemic endocrine environment. PLoS Genet. 2019 03; 15(3):e1008002. PMID: 30893315.
      View in: PubMed
    3. Patel Y, Soni M, Awgulewitsch A, Kern MJ, Liu S, Shah N, Singh UP, Chen H. Correction: Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis. Oncogene. 2019 01; 38(3):454. PMID: 30375491.
      View in: PubMed
    4. Patel Y, Soni M, Awgulewitsch A, Kern MJ, Liu S, Shah N, Singh UP, Chen H. Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis. Oncogene. 2019 01; 38(3):445-453. PMID: 30104710.
      View in: PubMed
    5. Yu M, Al-Dallal S, Al-Haj L, Panjwani S, McCartney AS, Edwards SM, Manjunath P, Walker C, Awgulewitsch A, Hentges KE. Transcriptional regulation of the proto-oncogene Zfp521 by SPI1 (PU.1) and HOXC13. Genesis. 2016 Oct; 54(10):519-533. PMID: 27506447.
      View in: PubMed
    6. Potter CS, Kern MJ, Baybo MA, Pruett ND, Godwin AR, Sundberg JP, Awgulewitsch A. Dysregulated expression of sterol O-acyltransferase 1 (Soat1) in the hair shaft of Hoxc13 null mice. Exp Mol Pathol. 2015 Dec; 99(3):441-4. PMID: 26321246.
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    7. Visconti RP, Awgulewitsch A. Topographic patterns of vascular disease: HOX proteins as determining factors? World J Biol Chem. 2015 Aug 26; 6(3):65-70. PMID: 26322165.
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    8. Sundberg JP, Awgulewitsch A, Pruett ND, Potter CS, Silva KA, Stearns TM, Sundberg BA, Muñoz MW, Cuasnicu PS, King LE, Rice RH. Crisp1 and alopecia areata in C3H/HeJ mice. Exp Mol Pathol. 2014 Dec; 97(3):525-8. PMID: 25446841.
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    9. Awgulewitsch A, Majesky MW. Interpreting inflammation: smooth muscle positional identity and nuclear factor-?B signaling. Arterioscler Thromb Vasc Biol. 2013 Jun; 33(6):1113-5. PMID: 23677878.
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    10. Pruett ND, Hajdu Z, Zhang J, Visconti RP, Kern MJ, Wellik DM, Majesky MW, Awgulewitsch A. Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling. Biol Open. 2012 May 15; 1(5):430-5. PMID: 23213434.
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    11. Potter CS, Pruett ND, Kern MJ, Baybo MA, Godwin AR, Potter KA, Peterson RL, Sundberg JP, Awgulewitsch A. The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation. J Invest Dermatol. 2011 Apr; 131(4):828-37. PMID: 21191399.
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    12. Wu B, Potter CS, Silva KA, Liang Y, Reinholdt LG, Alley LM, Rowe LB, Roopenian DC, Awgulewitsch A, Sundberg JP. Mutations in sterol O-acyltransferase 1 (Soat1) result in hair interior defects in AKR/J mice. J Invest Dermatol. 2010 Nov; 130(11):2666-8. PMID: 20574437.
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    13. Bazzi H, Demehri S, Potter CS, Barber AG, Awgulewitsch A, Kopan R, Christiano AM. Desmoglein 4 is regulated by transcription factors implicated in hair shaft differentiation. Differentiation. 2009 Dec; 78(5):292-300. PMID: 19683850.
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    14. Giehl KA, Potter CS, Wu B, Silva KA, Rowe LB, Awgulewitsch A, Sundberg JP. Hair interior defect in AKR/J mice. Clin Exp Dermatol. 2009 Jun; 34(4):509-17. PMID: 19522984.
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    15. Mentzer SE, Sundberg JP, Awgulewitsch A, Chao HH, Carpenter DA, Zhang WD, Rinchik EM, You Y. The mouse hairy ears mutation exhibits an extended growth (anagen) phase in hair follicles and altered Hoxc gene expression in the ears. Vet Dermatol. 2008 Dec; 19(6):358-67. PMID: 19037915.
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    16. Pruett ND, Visconti RP, Jacobs DF, Scholz D, McQuinn T, Sundberg JP, Awgulewitsch A. Evidence for Hox-specified positional identities in adult vasculature. BMC Dev Biol. 2008 Sep 30; 8:93. PMID: 18826643.
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    17. Potter CS, Peterson RL, Barth JL, Pruett ND, Jacobs DF, Kern MJ, Argraves WS, Sundberg JP, Awgulewitsch A. Evidence that the satin hair mutant gene Foxq1 is among multiple and functionally diverse regulatory targets for Hoxc13 during hair follicle differentiation. J Biol Chem. 2006 Sep 29; 281(39):29245-55. PMID: 16835220.
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    18. Peterson RL, Tkatchenko TV, Pruett ND, Potter CS, Jacobs DF, Awgulewitsch A. Epididymal cysteine-rich secretory protein 1 encoding gene is expressed in murine hair follicles and downregulated in mice overexpressing Hoxc13. J Investig Dermatol Symp Proc. 2005 Dec; 10(3):238-42. PMID: 16382673.
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    19. Pruett ND, Tkatchenko TV, Jave-Suarez L, Jacobs DF, Potter CS, Tkatchenko AV, Schweizer J, Awgulewitsch A. Krtap16, characterization of a new hair keratin-associated protein (KAP) gene complex on mouse chromosome 16 and evidence for regulation by Hoxc13. J Biol Chem. 2004 Dec 03; 279(49):51524-33. PMID: 15385554.
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    20. Awgulewitsch A. Hox in hair growth and development. Naturwissenschaften. 2003 May; 90(5):193-211. PMID: 12743702.
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    21. Shang L, Pruett ND, Awgulewitsch A. Hoxc12 expression pattern in developing and cycling murine hair follicles. Mech Dev. 2002 May; 113(2):207-10. PMID: 11960714.
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    22. Tkatchenko AV, Visconti RP, Shang L, Papenbrock T, Pruett ND, Ito T, Ogawa M, Awgulewitsch A. Overexpression of Hoxc13 in differentiating keratinocytes results in downregulation of a novel hair keratin gene cluster and alopecia. Development. 2001 May; 128(9):1547-58. PMID: 11290294.
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    23. Papenbrock T, Visconti RP, Awgulewitsch A. Loss of fibula in mice overexpressing Hoxc11. Mech Dev. 2000 Apr; 92(2):113-23. PMID: 10727851.
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    24. Papenbrock T, Peterson RL, Lee RS, Hsu T, Kuroiwa A, Awgulewitsch A. Murine Hoxc-9 gene contains a structurally and functionally conserved enhancer. Dev Dyn. 1998 Aug; 212(4):540-7. PMID: 9707327.
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    25. Peterson RL, Papenbrock T, Davda MM, Awgulewitsch A. The murine Hoxc cluster contains five neighboring AbdB-related Hox genes that show unique spatially coordinated expression in posterior embryonic subregions. Mech Dev. 1994 Sep; 47(3):253-60. PMID: 7848872.
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    26. Awgulewitsch A, Jacobs D. Deformed autoregulatory element from Drosophila functions in a conserved manner in transgenic mice. Nature. 1992 Jul 23; 358(6384):341-4. PMID: 1353608.
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    27. Hirayama F, Shih JP, Awgulewitsch A, Warr GW, Clark SC, Ogawa M. Clonal proliferation of murine lymphohemopoietic progenitors in culture. Proc Natl Acad Sci U S A. 1992 Jul 01; 89(13):5907-11. PMID: 1631072.
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    28. Peterson RL, Jacobs DF, Awgulewitsch A. Hox-3.6: isolation and characterization of a new murine homeobox gene located in the 5' region of the Hox-3 cluster. Mech Dev. 1992 May; 37(3):151-66. PMID: 1353983.
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    29. Awgulewitsch A, Bieberich C, Bogarad L, Shashikant C, Ruddle FH. Structural analysis of the Hox-3.1 transcription unit and the Hox-3.2--Hox-3.1 intergenic region. Proc Natl Acad Sci U S A. 1990 Aug; 87(16):6428-32. PMID: 1696731.
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    30. Awgulewitsch A, Jacobs D. Differential expression of Hox 3.1 protein in subregions of the embryonic and adult spinal cord. Development. 1990 Mar; 108(3):411-20. PMID: 1971213.
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    31. Bogarad LD, Utset MF, Awgulewitsch A, Miki T, Hart CP, Ruddle FH. The developmental expression pattern of a new murine homeo box gene: Hox-2.5. Dev Biol. 1989 Jun; 133(2):537-49. PMID: 2567250.
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    32. Hart CP, Awgulewitsch A, Fainsod A, McGinnis W, Ruddle FH. Homeo box gene complex on mouse chromosome 11: molecular cloning, expression in embryogenesis, and homology to a human homeo box locus. Cell. 1985 Nov; 43(1):9-18. PMID: 3000607.
      View in: PubMed
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