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Alice Pentland

TitleProfessor
InstitutionSchool of Medicine and Dentistry
DepartmentDermatology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 697
Rochester NY 14642
Other Positions
TitleChair
InstitutionSchool of Medicine and Dentistry
DepartmentDermatology

TitleDirector, Center for Future Health
InstitutionUniversity of Rochester Medical Center
DepartmentCenter for Future Health

 
 Awards And Honors
1996     Dermatology Award  | University of Rochester
1999 - 2014Training Program in Dermatological Research  | NIH
2000 - 2010PGE2 Receptor Function in Skin  | NIH
2006 - 2007President  | Society for Investigative Dermatology
2009     ACTS Study Section, Member  | National Institution of Health
 
 Overview
Research in the Pentland Lab addresses the role of prostaglandins in skin carcinogenesis and in cell differentiation. The role of these lipid mediators in the induction of squamous cell carcinoma of the skin is being studied in the context of ultraviolet light injury. Recent work has shown that significant contributions to tumor initiation and promotion may be made by eicosanoids (arachidonic acid and its metabolites). Most importantly, non-steroidal anti-inflammatory drugs (NSAIDs), which are inhibitors of prostaglandin synthesis, have been shown to have anti-tumor properties in humans. Unfortunately, NSAIDs chemoprevention is limited by NSAID side effects. However, new data shows the hormone metabolizing enzyme aldoketoreductase AKR1C3 is also inhibited by most NSAIDs, begging the question whether cyclooxygenase inhibition is actually the key target through which NSAIDs produce their cancer prevention effects. A potential role in cancer for AKR1C3 has been shown in many tumor types. AKR1C3 metabolizes the cyclooxygenase product PGH2 into PGF2alpha, as well as transforming PGD2 into 9alpha11betaPGF2. This activity can shunt prostaglandin metabolism away from pro-differentiation, pro-apoptotic mediators such as PGJ2. AKR1C3 is also the primary enzyme responsible for synthesis of 17Beta-estradiol and testosterone from their respective less active precursors, supporting its role in hormone sensitive tumors. Lastly, AKR1C3 is capable of supporting redox cycling, which can produce mutations that could promote carcinogenesis.

We are testing the hypothesis that AKR1C3 is an important therapeutic target regulating SCC growth, due to PGF2alpha mediated signaling, redox and hormonal metabolic effects on SCC apoptosis, proliferation or invasion. We seek to determine whether this action is distinct from cancer reduction produced by cyclooxygenase. Current work addresses whether AKR1C3 expression is correlated with degree of tumor malignancy, and examines the relative importance of prostanoid metabolism, hormones and oxidative stress in human SCC-derived cell lines. In vivo models are also in use to understand the relative importance of these AKR1C3 activities.

 
 Selected Publications
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  1. Pentland A. Building social and scientific networks to grow our global skin biology community. J Invest Dermatol. 2013 Nov; 133(11):2497-9.
    View in: PubMed
  2. Poligone B, Hayden MS, Chen L, Pentland AP, Jimi E, Ghosh S. A Role for NF-?B Activity in Skin Hyperplasia and the Development of Keratoacanthomata in Mice. PLoS One. 2013; 8(8):e71887.
    View in: PubMed
  3. Ryan JL, Heckler CE, Ling M, Katz A, Williams JP, Pentland AP, Morrow GR. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res. 2013 Jul; 180(1):34-43.
    View in: PubMed
  4. Cummings RJ, Gerber SA, Judge JL, Ryan JL, Pentland AP, Lord EM. Exposure to Ionizing Radiation Induces the Migration of Cutaneous Dendritic Cells by a CCR7-Dependent Mechanism. J Immunol. 2012 Nov 1; 189(9):4247-57.
    View in: PubMed
  5. Pentland AP, Hall RP, Yancey KB. Happy birthday, Society for Investigative Dermatology. J Invest Dermatol. 2012 Mar; 132(3 Pt 1):495.
    View in: PubMed
  6. Pentland AP, Connolly NL, Fahner-Vihtelic JE. Patents and growth. J Invest Dermatol. 2012 Mar; 132(3 Pt 2):1037-41.
    View in: PubMed
  7. Mantel A, Carpenter-Mendini AB, Vanbuskirk JB, De Benedetto A, Beck LA, Pentland AP. Aldo-keto reductase 1C3 is expressed in differentiated human epidermis, affects keratinocyte differentiation, and is upregulated in atopic dermatitis. J Invest Dermatol. 2012 Apr; 132(4):1103-10.
    View in: PubMed
  8. Fuhrmann TL, Ignatovich YV, Pentland A. Cutaneous metastatic disease: Burkitt lymphoma. J Am Acad Dermatol. 2011 Jun; 64(6):1196-7.
    View in: PubMed
  9. Elmets CA, Viner JL, Pentland AP, Cantrell W, Lin HY, Bailey H, Kang S, Linden KG, Heffernan M, Duvic M, Richmond E, Elewski BE, Umar A, Bell W, Gordon GB. Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2010 Dec 15; 102(24):1835-44.
    View in: PubMed
  10. Gonzales UP, Scott GA, Briones AJ, Pentland AP. Remote hemorrhagic bullae occurring in a patient treated with subcutaneous heparin. Arch Dermatol. 2009 May; 145(5):604-5.
    View in: PubMed
  11. Mortensen LJ, Oberdörster G, Pentland AP, Delouise LA. In vivo skin penetration of quantum dot nanoparticles in the murine model: the effect of UVR. Nano Lett. 2008 Sep; 8(9):2779-87.
    View in: PubMed
  12. Horwitz CM, Mueller M, Wiley D, Tentler A, Bocko M, Chen L, Leibovici A, Quinn J, Shar A, Pentland AP. Is home health technology adequate for proactive self-care? Methods Inf Med. 2008; 47(1):58-62.
    View in: PubMed
  13. Erdle BJ, Brouxhon S, Kaplan M, Vanbuskirk J, Pentland AP. Effects of continuous-wave (670-nm) red light on wound healing. Dermatol Surg. 2008 Mar; 34(3):320-5.
    View in: PubMed
  14. Brouxhon S, Kyrkanides S, O'Banion MK, Johnson R, Pearce DA, Centola GM, Miller JN, McGrath KH, Erdle B, Scott G, Schneider S, VanBuskirk J, Pentland AP. Sequential down-regulation of E-cadherin with squamous cell carcinoma progression: loss of E-cadherin via a prostaglandin E2-EP2 dependent posttranslational mechanism. Cancer Res. 2007 Aug 15; 67(16):7654-64.
    View in: PubMed
  15. Ryan JL, Bole C, Hickok JT, Figueroa-Moseley C, Colman L, Khanna RC, Pentland AP, Morrow GR. Post-treatment skin reactions reported by cancer patients differ by race, not by treatment or expectations. Br J Cancer. 2007 Jul 2; 97(1):14-21.
    View in: PubMed
  16. Taverna JA, Radfar A, Pentland A, Poggioli G, Demierre MF. Case reports: nodular vasculitis responsive to mycophenolate mofetil. J Drugs Dermatol. 2006 Nov-Dec; 5(10):992-3.
    View in: PubMed
  17. Brouxhon S, Konger RL, VanBuskirk J, Sheu TJ, Ryan J, Erdle B, Almudevar A, Breyer RM, Scott G, Pentland AP. Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness. J Invest Dermatol. 2007 Feb; 127(2):439-46.
    View in: PubMed
  18. Okunieff P, Xu J, Hu D, Liu W, Zhang L, Morrow G, Pentland A, Ryan JL, Ding I. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines. Int J Radiat Oncol Biol Phys. 2006 Jul 1; 65(3):890-8.
    View in: PubMed
  19. Maloo M, Abt P, Kashyap R, Younan D, Zand M, Orloff M, Jain A, Pentland A, Scott G, Bozorgzadeh A. Nephrogenic systemic fibrosis among liver transplant recipients: a single institution experience and topic update. Am J Transplant. 2006 Sep; 6(9):2212-7.
    View in: PubMed
  20. Scott GA, Jacobs SE, Pentland AP. sPLA2-X stimulates cutaneous melanocyte dendricity and pigmentation through a lysophosphatidylcholine-dependent mechanism. J Invest Dermatol. 2006 Apr; 126(4):855-61.
    View in: PubMed
  21. Konger RL, Brouxhon S, Partillo S, VanBuskirk J, Pentland AP. The EP3 receptor stimulates ceramide and diacylglycerol release and inhibits growth of primary keratinocytes. Exp Dermatol. 2005 Dec; 14(12):914-22.
    View in: PubMed
  22. Rodriguez-Burford C, Tu JH, Mercurio M, Carey D, Han R, Gordon G, Niwas S, Bell W, Elmets CA, Grizzle W, Pentland AP. Selective cyclooxygenase-2 inhibition produces heterogeneous erythema response to ultraviolet irradiation. J Invest Dermatol. 2005 Dec; 125(6):1317-20.
    View in: PubMed
  23. Konger RL, Billings SD, Thompson AB, Morimiya A, Ladenson JH, Landt Y, Pentland AP, Badve S. Immunolocalization of low-affinity prostaglandin E receptors, EP and EP, in adult human epidermis. J Invest Dermatol. 2005 May; 124(5):965-70.
    View in: PubMed
  24. Scott G, Jacobs S, Leopardi S, Anthony FA, Learn D, Malaviya R, Pentland A. Effects of PGF2alpha on human melanocytes and regulation of the FP receptor by ultraviolet radiation. Exp Cell Res. 2005 Apr 1; 304(2):407-16.
    View in: PubMed
  25. Pentland AP, Scott G, VanBuskirk J, Tanck C, LaRossa G, Brouxhon S. Cyclooxygenase-1 deletion enhances apoptosis but does not protect against ultraviolet light-induced tumors. Cancer Res. 2004 Aug 15; 64(16):5587-91.
    View in: PubMed
  26. Tripp CS, Blomme EA, Chinn KS, Hardy MM, LaCelle P, Pentland AP. Epidermal COX-2 induction following ultraviolet irradiation: suggested mechanism for the role of COX-2 inhibition in photoprotection. J Invest Dermatol. 2003 Oct; 121(4):853-61.
    View in: PubMed
  27. Rys-Sikora KE, Pentland AP, Konger RL. Pertussis toxin-sensitive secretory phospholipase A2 expression and motility in activated primary human keratinocytes. J Invest Dermatol. 2003 Jan; 120(1):86-95.
    View in: PubMed
  28. Konger RL, Scott GA, Landt Y, Ladenson JH, Pentland AP. Loss of the EP2 prostaglandin E2 receptor in immortalized human keratinocytes results in increased invasiveness and decreased paxillin expression. Am J Pathol. 2002 Dec; 161(6):2065-78.
    View in: PubMed
  29. Pentland AP. Cyclooxygenase inhibitors for skin cancer prevention: are they beneficial enough? Arch Dermatol. 2002 Jun; 138(6):823-4.
    View in: PubMed
  30. Pentland AP, Pentland AP. Inventing the future--tools for self health. Stud Health Technol Inform. 2002; 80:19-25.
    View in: PubMed
  31. Scott G, Deng A, Rodriguez-Burford C, Seiberg M, Han R, Babiarz L, Grizzle W, Bell W, Pentland A. Protease-activated receptor 2, a receptor involved in melanosome transfer, is upregulated in human skin by ultraviolet irradiation. J Invest Dermatol. 2001 Dec; 117(6):1412-20.
    View in: PubMed
  32. Rys-Sikora KE, Konger RL, Schoggins JW, Malaviya R, Pentland AP. Coordinate expression of secretory phospholipase A(2) and cyclooxygenase-2 in activated human keratinocytes. Am J Physiol Cell Physiol. 2000 Apr; 278(4):C822-33.
    View in: PubMed
  33. Pentland AP, Schoggins JW, Scott GA, Khan KN, Han R. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis. 1999 Oct; 20(10):1939-44.
    View in: PubMed
  34. Buckman SY, Koki AT, Edwards DA, Pentland AP. Immunohistochemical analysis of cyclooxygenase expression in human skin. Methods Mol Biol. 1999; 120:35-43.
    View in: PubMed
  35. Guan Z, Buckman SY, Pentland AP, Templeton DJ, Morrison AR. Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway. J Biol Chem. 1998 May 22; 273(21):12901-8.
    View in: PubMed
  36. Buckman SY, Gresham A, Hale P, Hruza G, Anast J, Masferrer J, Pentland AP. COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Carcinogenesis. 1998 May; 19(5):723-9.
    View in: PubMed
  37. Konger RL, Malaviya R, Pentland AP. Growth regulation of primary human keratinocytes by prostaglandin E receptor EP2 and EP3 subtypes. Biochim Biophys Acta. 1998 Feb 4; 1401(2):221-34.
    View in: PubMed
  38. Ruiz N, Wang B, Pentland A, Caparon M. Streptolysin O and adherence synergistically modulate proinflammatory responses of keratinocytes to group A streptococci. Mol Microbiol. 1998 Jan; 27(2):337-46.
    View in: PubMed
  39. Wang B, Ruiz N, Pentland A, Caparon M. Keratinocyte proinflammatory responses to adherent and nonadherent group A streptococci. Infect Immun. 1997 Jun; 65(6):2119-26.
    View in: PubMed
  40. Sudbeck BD, Pilcher BK, Pentland AP, Parks WC. Modulation of intracellular calcium levels inhibits secretion of collagenase 1 by migrating keratinocytes. Mol Biol Cell. 1997 May; 8(5):811-24.
    View in: PubMed
  41. Malaviya R, Morrison AR, Pentland AP. Histamine in human epidermal cells is induced by ultraviolet light injury. J Invest Dermatol. 1996 Apr; 106(4):785-9.
    View in: PubMed
  42. Gresham A, Masferrer J, Chen X, Leal-Khouri S, Pentland AP. Increased synthesis of high-molecular-weight cPLA2 mediates early UV-induced PGE2 in human skin. Am J Physiol. 1996 Apr; 270(4 Pt 1):C1037-50.
    View in: PubMed
  43. Pentland AP. Signal transduction mechanisms in photocarcinogenesis. Photochem Photobiol. 1996 Apr; 63(4):379-80.
    View in: PubMed
  44. Chen X, Gresham A, Morrison A, Pentland AP. Oxidative stress mediates synthesis of cytosolic phospholipase A2 after UVB injury. Biochim Biophys Acta. 1996 Jan 5; 1299(1):23-33.
    View in: PubMed
  45. Andley UP, Becker B, Hebert JS, Reddan JR, Morrison AR, Pentland AP. Enhanced prostaglandin synthesis after ultraviolet-B exposure modulates DNA synthesis of lens epithelial cells and lowers intraocular pressure in vivo. Invest Ophthalmol Vis Sci. 1996 Jan; 37(1):142-53.
    View in: PubMed
  46. Pentland AP, Shapiro SD, Welgus HG. Agonist-induced expression of tissue inhibitor of metalloproteinases and metalloproteinases by human macrophages is regulated by endogenous prostaglandin E2 synthesis. J Invest Dermatol. 1995 Jan; 104(1):52-7.
    View in: PubMed
  47. Sudbeck BD, Parks WC, Welgus HG, Pentland AP. Collagen-stimulated induction of keratinocyte collagenase is mediated via tyrosine kinase and protein kinase C activities. J Biol Chem. 1994 Nov 25; 269(47):30022-9.
    View in: PubMed
  48. Okada N, Pentland AP, Falk P, Caparon MG. M protein and protein F act as important determinants of cell-specific tropism of Streptococcus pyogenes in skin tissue. J Clin Invest. 1994 Sep; 94(3):965-77.
    View in: PubMed
  49. Saarialho-Kere UK, Pentland AP, Birkedal-Hansen H, Parks WC, Welgus HG. Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds. J Clin Invest. 1994 Jul; 94(1):79-88.
    View in: PubMed
  50. Miller CC, Hale P, Pentland AP. Ultraviolet B injury increases prostaglandin synthesis through a tyrosine kinase-dependent pathway. Evidence for UVB-induced epidermal growth factor receptor activation. J Biol Chem. 1994 Feb 4; 269(5):3529-33.
    View in: PubMed
  51. Andley UP, Hebert JS, Morrison AR, Reddan JR, Pentland AP. Modulation of lens epithelial cell proliferation by enhanced prostaglandin synthesis after UVB exposure. Invest Ophthalmol Vis Sci. 1994 Feb; 35(2):374-81.
    View in: PubMed
  52. Hussain H, Shornick LP, Shannon VR, Wilson JD, Funk CD, Pentland AP, Holtzman MJ. Epidermis contains platelet-type 12-lipoxygenase that is overexpressed in germinal layer keratinocytes in psoriasis. Am J Physiol. 1994 Jan; 266(1 Pt 1):C243-53.
    View in: PubMed
  53. Pentland AP. Active oxygen mechanisms of UV inflammation. Adv Exp Med Biol. 1994; 366:87-97.
    View in: PubMed
  54. Saarialho-Kere UK, Kovacs SO, Pentland AP, Olerud JE, Welgus HG, Parks WC. Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing. J Clin Invest. 1993 Dec; 92(6):2858-66.
    View in: PubMed
  55. Shapiro SD, Kobayashi DK, Pentland AP, Welgus HG. Induction of macrophage metalloproteinases by extracellular matrix. Evidence for enzyme- and substrate-specific responses involving prostaglandin-dependent mechanisms. J Biol Chem. 1993 Apr 15; 268(11):8170-5.
    View in: PubMed
  56. Kang-Rotondo CH, Miller CC, Morrison AR, Pentland AP. Enhanced keratinocyte prostaglandin synthesis after UV injury is due to increased phospholipase activity. Am J Physiol. 1993 Feb; 264(2 Pt 1):C396-401.
    View in: PubMed
  57. Hruza LL, Pentland AP. Mechanisms of UV-induced inflammation. J Invest Dermatol. 1993 Jan; 100(1):35S-41S.
    View in: PubMed
  58. Pentland AP, Morrison AR, Jacobs SC, Hruza LL, Hebert JS, Packer L. Tocopherol analogs suppress arachidonic acid metabolism via phospholipase inhibition. J Biol Chem. 1992 Aug 5; 267(22):15578-84.
    View in: PubMed
  59. Schiro JA, Chan BM, Roswit WT, Kassner PD, Pentland AP, Hemler ME, Eisen AZ, Kupper TS. Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Cell. 1991 Oct 18; 67(2):403-10.
    View in: PubMed
  60. Pentland AP, Jacobs SC. Bradykinin-induced prostaglandin synthesis is enhanced in keratinocytes and fibroblasts by UV injury. Am J Physiol. 1991 Sep; 261(3 Pt 2):R543-7.
    View in: PubMed
  61. Udey MC, Peck RD, Pentland AP, Schreiner GF, Lefkowith JB. Antigen-presenting cells in essential fatty acid-deficient murine epidermis: keratinocytes bearing class II (Ia) antigens may potentiate the accessory cell function of Langerhans cells. J Invest Dermatol. 1991 Jun; 96(6):950-8.
    View in: PubMed
  62. Pentland AP, Mahoney M, Jacobs SC, Holtzman MJ. Enhanced prostaglandin synthesis after ultraviolet injury is mediated by endogenous histamine stimulation. A mechanism for irradiation erythema. J Clin Invest. 1990 Aug; 86(2):566-74.
    View in: PubMed
  63. Pentland AP, Mahoney MG. Keratinocyte prostaglandin synthesis is enhanced by IL-1. J Invest Dermatol. 1990 Jan; 94(1):43-6.
    View in: PubMed
  64. Holtzman MJ, Turk J, Pentland A. A regiospecific monooxygenase with novel stereopreference is the major pathway for arachidonic acid oxygenation in isolated epidermal cells. J Clin Invest. 1989 Nov; 84(5):1446-53.
    View in: PubMed
  65. Remmler D, Thomas JR, Mazoujian G, Pentland A, Schechtman K, Favors S, Bauer E. Use of injectable cultured human fibroblasts for percutaneous tissue implantation. An experimental study. Arch Otolaryngol Head Neck Surg. 1989 Jul; 115(7):837-44.
    View in: PubMed
  66. Holtzman MJ, Pentland A, Baenziger NL, Hansbrough JR. Heterogeneity of cellular expression of arachidonate 15-lipoxygenase: implications for biological activity. Biochim Biophys Acta. 1989 Jun 8; 1003(2):204-8.
    View in: PubMed
  67. Pentland AP. Collagen lattice effects on fibroblast arachidonic acid metabolism. J Cell Physiol. 1989 May; 139(2):392-7.
    View in: PubMed
  68. HE CS, Wilhelm SM, Pentland AP, Marmer BL, Grant GA, Eisen AZ, Goldberg GI. Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. Proc Natl Acad Sci U S A. 1989 Apr; 86(8):2632-6.
    View in: PubMed
  69. Bauer EA, Pentland AP, Kronberger A, Wilhelm SM, Goldberg GI, Welgus HG, Eisen AZ. Keratinocyte- and tumor-derived inducers of collagenase. Ann N Y Acad Sci. 1988; 548:174-9.
    View in: PubMed
  70. Eisen AZ, Pentland AP, Bauer EA, Goldberg GI. Behavior of epidermolysis bullosa fibroblasts in a hydrated collagen lattice. J Invest Dermatol. 1987 Jun; 88(6):741-6.
    View in: PubMed
  71. Pentland AP, George J, Moran C, Needleman P. Cellular confluence determines injury-induced prostaglandin E2 synthesis by human keratinocyte cultures. Biochim Biophys Acta. 1987 May 13; 919(1):71-8.
    View in: PubMed
  72. Pentland AP, Marcelo CL, Jordan MA, Voorhees JJ. Effects of gas tension on epidermal keratinocyte DNA synthesis and prostaglandin production. J Invest Dermatol. 1986 Feb; 86(2):177-80.
    View in: PubMed
  73. Pentland AP, Needleman P. Modulation of keratinocyte proliferation in vitro by endogenous prostaglandin synthesis. J Clin Invest. 1986 Jan; 77(1):246-51.
    View in: PubMed
  74. Pentland AP, Anderson TF. Plantar fibromatosis responds to intralesional steroids. J Am Acad Dermatol. 1985 Jan; 12(1 Pt 2):212-4.
    View in: PubMed
  75. Fairley JA, Pentland AP, Voorhees JJ. Urticaria pigmentosa responsive to nifedipine. J Am Acad Dermatol. 1984 Oct; 11(4 Pt 2):740-3.
    View in: PubMed
  76. Pentland AP, Marcelo CL. Modulation of proliferation in epidermal keratinocyte cultures by lowered oxygen tension. Exp Cell Res. 1983 Apr 15; 145(1):31-43.
    View in: PubMed

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