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The Department of Dermatology deals with all aspects of the biology and diseases of the skin.

Department of Dermatology
 

Dennis Roop, Ph.D.

Professor of Dermatology and Director of the Gates Stem Cell Center


Dr. Dennis Roop
 

Professor of Dermatology, Department of Dermatology
Director and Chair, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology

University of Colorado Denver
Anschutz Medical Campus
12800 E. 19th Avenue
Mail Stop #8320
Aurora, CO 80045
Email: Dennis.Roop@ucdenver.edu
 

Research Interests: 

My laboratory has a long standing interest in identifying genes required for normal skin development and understanding how they function.  We have discovered that defects in some of these genes cause inherited skin diseases characterized by a very fragile skin, which blisters easily and may result in neonatal death.  Defects in other genes required for normal skin development predispose individuals to develop skin cancer.
We are currently generating induced Pluripotent Stem Cells (iPSCs) from patients with inherited skin fragility syndromes using methods which do not require viral vectors, and determining whether genome editing techniques can be used to correct the genetic defect in these patient-specific iPSCs. Our ultimate goal is return keratinocytes derived from genetically corrected iPSCs to the same patient as an autograft.  My laboratory is also isolating and characterizing skin cancer stem cells.  An improved understanding of cancer stem cells could result in the development of novel therapeutic strategies that specifically target cancer stem cells for destruction and prevent tumor recurrence.   

Recent publications: 

  1. Mehrel, T., Hohl, D., Rothnagel, J.A., Longley, M.A., Bundman, D., Cheng, C., Lichti, U., Bisher, M.E., Steven, A.C., Steinert, P.M., Yuspa, S.H., and Roop, D.R. (1990) Identification of a major keratinocyte cell envelope protein, loricrin. Cell 61:1103‑1112. PMID:2190691
  1. Rothnagel, J.A., Dominey, A.M., Dempsey, L.D., Longley, M.A., Greenhalgh, D.A., Gagne, T.A., Huber, M., Frenk, E., Hohl, D., and Roop, D.R. (1992) Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis.  Science 257, 1128-1130.  PMID 1380725
  2. Rothnagel, J.A., Traupe, H., Wojcik, S., Huber, M., Hohl, D., Pittelkow, M.R., Saeki, H., Ishibashi, Y. and Roop, D.R. (1994) Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Seimens.  Nature Genetics 7:485-490.  PMID 7524919.
  3. Mills, A.A., Zheng, B., Wang, X.-J., Vogel, H., Roop, D.R., Bradley, A. (1999) p63, a p53 homologue required for limb and epidermal morphogenesis. Nature 398:708 -713. PMID:10227293
  4. Koch, P.J., de Viragh, P.A., Scharer, L. Bundman, D., Longley, M.A., Bickenbach, J., Kawachi, Y., Suga, Y., Zhou, Z., Huber, M., Hohl, D., Jarnik, M., Steven, A.C. and Roop, D.R. (2000) Lessons from loricrin-deficient mice: Compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein. J. Cell Biol. 151:389-400. PMID:11038185
  5. Suga, Y., Jarnik, M., Attar, P.S., Longley, M.A., Bundman, D.S., Steven, A.C., Koch, P.J. and Roop, D.R. (2000) Transgenic mice expressing a mutant form of loricrin reveal the molecular basis of the skin diseases, Vohwinkel syndrome and progressive symmetric erythrokeratoderma. J. Cell Biol. 151:401-412. PMID:11038186
  6. Arin, M.J., Longley, M.A., Wang, X.J. and Roop, D.R. (2001) Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders.  J. Cell Biol. 152: 645-649.  PMID 11157989
  7. Cao, T., Longley, M.A., Wang, X.J. and Roop, D.R. (2001) An inducible mouse model for epidermolysis bullosa simplex:  Implications for gene therapy.  J. Cell Biol. 152: 651-656. PMID 11157990
  8. Waikel, R., Kawachi, Y., Waikel, P.A., Wang, X.-J., and Roop, D.R. (2001) Deregulated Expression of c Myc Depletes Epidermal Stem Cells. Nature Genetics 28:165-168. PMID:11381265
  9. Wakabayashi, N., Itoh, K., Wakabayashi, J., Motohashi, H., Noda, S., Takahashi, S., Imakado, S., Kotsuji, T., Otsuka, F., Roop, D.R., Harada, T., Engel, J.D., Yamamoto, M. (2003) Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nature Genetics 35:238-245. PMID:14517554
  10. Koster, M.I., Kim, S., Mills, A.A., DeMayo, F.J., Roop, D.R. (2004) p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev. 18:126-131. PMID:14729569
  11. Sil, A.K., Maeda, S., Sano, Y., Roop, D.R. and Karin, M. (2004) IkappaB kinase-alpha acts in the epidermis to control skeletal and craniofacial morphogenesis. Nature 428:660-664. PMID:15071597 
  12. Caulin, C., Nguyen, T., Longley, M.A., Zhou, Z., Wang, X.J., and Roop, D.R. (2004) Inducible activation of oncogenic K-ras results in tumor formation in the oral cavity. Cancer Res. 64:5054-5058.
  13. Koster, M.I. and Roop, D.R. (2005) Asymmetric cell division in skin development: a new look at an old observation. Dev. Cell 9:444-446.
  14. Koster, M.I., Kim, S., Huang, J., Williams, T. and Roop, D.R. (2005) TAp63α induces AP-2γ as an early event in epidermal morphogenesis. Dev. Biol. 289(1): 253-261, 2006.
  15. Koster, M.I., Lu, S.L., White, L.D., Wang, X.J., and Roop, D.R. (2006) Reactivation of Developmentally Expressed p63 Isoforms Predisposes to Tumor Development and Progression. Cancer Res. 66(8):3981-3986.
  16. Koster, M.I., Dai, D., Marinari, B. Sano, Y., Costanzo, A., Karin, M. and Roop, D.R. (2007) p63 induces key target genes required for epidermal morphogenesis. Proc. Natl. Acad. Sci. U.S.A. 104(9):3255-60. PMID:17360634
  17. Caulin, C., Nguyen, T., Lang, G.A., Goepfert, T.M., Brinkley, B.R., Cai, W.W., Lozano, G., Roop, D.R. (2007) An inducible mouse model for skin cancer reveals distinct roles for gain- and loss-of-function p53 mutations. J. Clin. Invest. 117(7):1893-1901. PMID:17607363
  18. Torchia EC, Chen Y, Sheng H, Katayama H, Fitzpatrick J, Brinkley WR, Caulin C, Sen S, Roop D.R. (2009) A Genetic Variant of Aurora Kinase A Promotes Genomic Instability Leading to Highly Malignant Skin Tumors. Cancer Res. 69:7207-7215. PMID:19738056
  19. Bilousova, G., Chen, J., Roop D.R. (2011) Differentiation of mouse induced pluripotent stem cells into a multipotent keratinocyte lineage. J Invest Dermatol. 131(4):857-64. PMID 21138087
  20. Bilousova G, Hyun Jun D, King KB, Delanghe S, Chick WS, Torchia EC, Chow KS, Klemm DJ, Roop DR, Majka SM. (2011) Osteoblasts Derived from Induced Pluripotent Stem Cells form Calcified Structures in Scaffolds both in vitro and in vitro. Stem Cells. 29(2):206-216.  PMID 21732479
  21. Torchia EC, Caulin C, Acin S, Terzian T, Kubick BJ, Box NF and Roop DR.  Myc, Aurora Kinase-A, and mutant p53R172H co-operate in a mouse model of metastatic skin carcinoma. Oncogene.  2011 Oct 3.  [Epub ahead of print] PMID: 21963848
  22. Huebner AJ, Dai D, Morasso M, Schmidt EE, Schäfer M, Werner S, Roop DR.  Amniotic fluid activates the nrf2/keap1 pathway to repair an epidermal barrier defect in utero.  Dev Cell. 2012 Dec 11;23(6):1238-46. PMID:23237955  PMCID:PMC3710685
  23. Torchia EC, Zhang L, Huebner AJ, Sen S, Roop DR.  Aurora kinase-A deficiency during skin development impairs cell division and stratification.  J Invest Dermatol. 2013 Jan;133(1):78-86.  Epub 2012 Jul 26.  PMID:22832491  PMCID:PMC3494779
  24. White RA, Neiman JM, Reddi A, Han G, Birlea S, Mitra D, Dionne L, Fernandez P, Murao K, Bian L, Keysar SB, Goldstein NB, Song N, Bornstein S, Han Z, Lu X, Wisell J, Li F, Song J, Lu SL, Jimeno A, Roop DR, Wang XJ. Epithelial stem cell mutations that promote squamous cell carcinoma metastasis. J Clin Invest. 2013 Sep 3. doi:pii: 65856. 10.1172/JCI65856. [Epub ahead of print] PMID: 23999427