Walter Holleran, PharmD

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Education

University of California, Santa Barbara, B.A., 1977, Biochemistry
University of California, Santa Barbara, M.A., 1979, Chemistry
University of California, San Francisco, Pharm.D., 1984, Pharmacology

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Professional Experience

• 1984-1985
  Postdoctoral Fellow, Cancer Pharmacology Laboratory, Children's Cancer Research Institute, Pacific Presbyterian Medical Center, San Francisco
• 1986-1988
  Postdoctoral Fellow, Cancer Research Institute, University of California, San Francisco
• 1988
  Assistant Research Biochemist, San Francisco State University, San Francisco
• 1989-1996
  Assistant Adjunct Professor, Department of Dermatology, U.C. San Francisco
• 1996-present
  Associate Adjunct Professor, Department of Dermatology, School of Medicine, U.C.S.F.
• 2000-present
  Associate Adjunct Professor (Joint Appointment), Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco
• 2005
  Member, UCSF Helen Diller Family Comprehensive Cancer Center, Cutaneous Oncology Program

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Honors & Awards

• From a total of 65
• Holleran WM, Williams ML, Gao WN, Elias PM. Serine-palmitoyl transferase activity in cultured human keratinocytes. J. Lipid Res. 31:1655-1661, 1990.
• Holleran WM, Feingold KR, Man M-Q, Gao WN, Lee JM, Elias PM Regulation of epidermal sphingolipid synthesis by permeability barrier function. J. Lipid. Res. 32:1151-1158, 1991.
• Holleran WM, Mao-Qiang M., Gao WN, Menon GK, Elias PM, Feingold KR. Sphingolipids are required for mammalian barrier function: Inhibition of sphingolipid synthesis delays barrier recovery. J. Clin. Invest. 88:1338-1345, 1991.
• Holleran WM, Takagi Y, Imokawa G, Jackson S, Lee J, Elias PM. β-Glucocerebrosidase activity in murine epidermis: Characterization & localization in relation to differentiation. J. Lipid Res., 33:1201-1209, 1992.
• Holleran WM, Takagi Y, Menon GK, Legler G, Feingold KR, Elias PM. Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability function. J. Clin. Invest. 91:1656-1664, 1993.
• Holleran WM, Ginns EI, Menon G, Grundmann J-U, Fartasch M, Elias PM, Sidransky E. Epidermal consequences of β-glucocerebrosidase deficiency: Permeability barrier alterations and basis for skin lesions in Type 2 Gaucher disease. J. Clin. Invest. 93:1756-1764, 1994.
• Holleran WM, Takagi Y, Menon GK, Jackson S, Lee JM, Feingold KR, Elias PM. Permeability barrier requirements regulate epidermal β-glucocerebrosidase. J. Lipid Res. 35:905-912, 1994.
• Holleran WM, Gao W, Feingold K, Elias, P. Localization of epidermal sphingolipid synthesis & serine palmitoyl transferase activity: Alterations imposed by permeability barrier requirements. Arch. Dermatol. Res. 287:254-258, 1995.
• Marsh NL, Elias PM, and Holleran WM. Enhancement of epidermal glucosylceramide content stimulates mitogenesis in murine epidermis. J. Clin. Invest. 95:2903-2909 1995.
• Sidransky E, Fartasch M, Lee RE, Metlay LA, Abella S, Zimran A, Gao WN, Elias PM, Ginns EI, and Holleran WM. Epidermal abnormalities distinguish type 2 from other types of Gaucher disease. Ped. Res. 39:134-141, 1996.
• Holleran WM, Galardy RE, Gao WN, Levy D, Tang, PC, Elias PM. Matrix metalloprotease inhibitors reduce phorbol-induced cutaneous inflammation and hyperproliferation. Arch. Derm. Res. 289:138-144, 1997.
• Hanley K, Jiang Y, Holleran WM, Elias PM, Williams M, Feingold KR. Glucosylceramide metabolism is regulated during normal and hormonally-stimulated epidermal barrier development in the rat. J. Lipid Res. 38:576-584, 1997
• Haratake A, Uchida Y, Schmuth M, Tanno O, Yasuda R, Epstein JH, Elias PM, Holleran WM. UVB-induced alterations in permeability barrier function: Roles for epidermal hyperproliferation and thymocyte-mediated response. J. Invest. Dermatol. 108:769-775, 1997.
• Harris IR, Farrell AM, Grunfeld C, Holleran WM, Elias, PM, Feingold, KR. Epidermal permeability barrier function regulates mRNA levels for key enzymes of cholesterol, fatty acid & ceramide synthesis. J Invest Dermatol. 109:783-787, 1997.
• Holleran WM, Uchida Y, Halkier-Sorensen L, Haratake A, Hara M, Epstein JH, Elias PM. Structural basis for the UVB-induced alterations in epidermal barrier function. Photoderm, Photoimmunol, Photomed., 13:117-128, 1997.
• Harris IR, Farrell AM, Holleran WM, Jackson S, Grunfeld C, Elias PM, Feingold KR. Parallel regulation of sterol regulatory element binding protein-2 & the enzymes of cholesterol & fatty acid synthesis but not ceramide synthesis in cultured human keratinocytes & murine epidermis. J Lipid Res, 39:412-422, 1998.
• Marchell NL, Uchida Y, Brown BE, Elias PM, Holleran WM. Glucosylceramides stimulate mitogenesis of aged murine epidermis. J. Invest. Dermatol, 110:383-387, 1998.
• Mauro T, Holleran WM, Grayson S, Gao WN, Kriehuber E, Man MQ, Feingold KR, Elias, PM. Barrier recovery is impeded at neutral pH, independent of ionic effects. Arch. Derm. Res., 290:215-222, 1998.
• Reissner K, Tayebi, N, Stubblefield BK, Koprivica V, Blitzer M, Holleran W, Cowan T, Almashanu S, Maddalena A, Karson EM, Sidransky E. Type 2 Gaucher disease with Hydrops Fetalis in an Ashkenazi Jewish family resulting from a novel recombinant allele & a rare splice junction mutation in the glucocerebrosidase locus. Molec Genet & Metab, 63:281-288, 1998.
• Memon RA, Holleran WM, Moser AH, Seki T, Uchida Y, Fuller J, Shigenaga JK, Grunfeld C, Feingold, KR. Endotoxin and cytokines increase hepatic sphingolipid biosynthesis & produce lipoproteins that are enriched in ceramides & sphingomyelin. Arteriosclerosis Thrombosis & Vascular Biol., 18:1257-1265, 1998
• Farrell AM, Nagiec MM, Dickson RC, Elias PM, Holleran WM. UVB irradiation stimulates sphingolipid synthesis in cultured human keratinocytes. J. Lipid Res., 39:2031-2038, 1998.
• Takagi Y, Kriehuber E, Imokawa G, Elias PM, Holleran WM. Localization of β-glucocerebrosidase in murine stratum corneum & epidermis: Relationship to other epidermal hydrolases. J. Lipid Res. 40:861-869, 1999.
• Doering T, Holleran WM, Potratz A, Vielhaber G, Elias PM, Suzuki K, Sandhoff K. Sphingolipid activator proteins (SAPs) are required for epidermal permeability barrier function. J Biol Chem 274:11036-11045, 1999.
• Memon RA, Holleran WM, Uchida Y, Moser AH, Ichikawa S, Hirabayashi Y, Grunfeld C, Feingold KR. Regulation of glycosphingolipid metabolism in liver during the acute phase response. J. Biol. Chem. 274:19707-19713, 1999.
• Behne M, Uchida Y, Seki T, Ortiz de Montellano P, Elias PM, Holleran WM. Omega-hydroxy-ceramides are required for epidermal permeability barrier homeostasis J. Invest. Dermatol. 114:185-192, 2000.
• Memon RA, Staprans I, Noor M, Holleran WM, Uchida Y, Moser AH, Feingold KR, Grunfeld C. Infection and inflammation induce LDL oxidation in vivo. Ateriosclerosis, Thrombosis, Vasc. Biol. 20:1536-1542, 2000.
• Schmuth M, Man MQ, Weber F, Gao WN, Feingold KR, Fritsch P, Elias PM, Holleran WM. Permeability barrier disorder in Niemann-Pick disease: Sphingomyelin-to-ceramide processing required for normal barrier homeostasis. J. Invest. Dermatol. 115:459-466, 2000.
• Elias PM, Fartasch M, Crumrine D, Uchida Y, Holleran WM. Origin of the corneocyte lipid envelope (CLE): Observations in Harlequin Ichthyosis and cultured human keratinocytes. J. Invest. Dermatol. 115:765-769, 2000.
• Uchida Y, Hara M, Nishio H, Sidransky E, Inoue S, Otsuka F, Suzuki A, Elias PM, Holleran WM., Hamanaka, S. Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J. Lipid Res. 41:2071-82, 2000.
• Memon RA, Holleran WM, Uchida Y, Moser AH, Grunfeld C, Feingold KR. Regulation of sphingolipid and glycosphingolipid metabolism in extra-hepatic tissues by endotoxin. J. Lipid Res. 42:452-459, 2001.
• Uchida Y, Behne M, Elias PM, Holleran WM. Vitamin C stimulates sphingolipid synthesis in normal human keratinocytes grown in submerged culture system. J. Invest. Dermatol. 117:1307-1313, 2001.
• Uchida Y, Murata S, Schmuth M, Behne M, Lee J-D, Ichikawa S, Elias PM, Hirabayashi Y, Holleran WM. Glucosyl-ceramide synthesis & expression protect against ceramide-induced stress. J. Lipid Res. 43:1293-1302, 2002
• Elias PM, Schmuth M, Uchida Y, Rice RH, Crumrine D, Komuves L, Feingold KR, Holleran WM. Basis for permeability barrier abnormality in lamellar ichthyosis Exp. Dermatol. 11:248-256, 2002.
• Bejaoui K, Uchida Y, Yasuda S, Ho M, Nishijima M, Brown RH, Holleran WM, Hanada K. Hereditary sensory neuropathy type 1 mutations confer dominant-negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis. J. Clin. Invest. 110:1301-1308, 2002.
• Behne MJ, Meyer J, Hanson KM, Barry NP, Crumrine D, Murata S, Clegg RW, Gratton E, Holleran WM, Elias PM, Mauro TM. NHE1 regulates the stratum corneum permeability barrier homeostasis: microenvironment acidification assessed with FLIM. J. Biol. Chem. 277:47399-406, 2002.
• Uchida Y, DiNardo A, Elias PM, Holleran WM. De novo synthesis of ceramide mediates Ultraviolet B irradiation-induced apoptosis in cultured human keratinocytes. J. Invest. Dermatol. 120:662-9, 2003.
• Behne MJ, Barry NP, Hanson KM, Aronchik I, Clegg RW, Gratton E, Feingold KR, Holleran WM, Elias PM, Mauro TM. Neonatal development of the stratum corneum pH gradient: Localization and mechanisms leading to emergence of optimal barrier function. J. Invest. Dermatol. 120:998-1006, 2003.
• Westerberg R, Tvrdik P, Unden A-B, Mansson J-E, Norlen L, Jakobsson A, Holleran WM, Asidi A, Flodby P, Toftgard R, Capecchi MR, Jacobsson A. Role for Elovl3 and fatty acid chain length in development of hair and skin function. J. Biol. Chem. 279:5621-9, 2004.
• Uchida Y, Itoh, M, Kitano T, Kondo T, Umehara H, Ichikawa S-I, Hirabayashi Y, Holleran WM, Okazaki, T. Ceramide reduction and transcriptional up-regulation of glucosylceramide synthase through doxorubicin-activated Sp1 in drug-resistant HL-60/ADR cells. Cancer Res 64:6271-79 2004.
• Hara-Chikuma M, Takeda J, Tarutani M, Uchida Y, Holleran WM, Endo Y, Elias PM, Inoue S. Epidermal-specific defect of GPI anchor in Pig-a Null mice results in Harlequin ichthyosis-like features. J. Invest. Dermatol. 123:464-69, 2004.
• Ting SB, Caddy J, Hislop K, Wilanowski T, Auden A, Zhao L, Ellis S, Kaur P, Uchida Y, Elias PM, Holleran WM, Cunningham JM, Jane SM. Mouse Grhl3, a homolog of Drosophila grainyhead, is essential for surface barrier formation and wound healing. Science , 308: 411-413, 2005.

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Selected Publications

1. Park K, Elias PM, Shin KO, Lee YM, Hupe M, Borkowski AW, Gallo RL, Saba J, Holleran WM, Uchida Y. A novel role of a lipid species, sphingosine-1-phosphate, in epithelial innate immunity. Mol Cell Biol. 2013 Feb; 33(4):752-62.
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2. Goto-Inoue N, Hayasaka T, Zaima N, Nakajima K, Holleran WM, Sano S, Uchida Y, Setou M. Imaging mass spectrometry visualizes ceramides and the pathogenesis of dorfman-chanarin syndrome due to ceramide metabolic abnormality in the skin. PLoS One. 2012; 7(11):e49519.
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3. Celli A, Mackenzie DS, Zhai Y, Tu CL, Bikle DD, Holleran WM, Uchida Y, Mauro TM. SERCA2-controlled Ca²+-dependent keratinocyte adhesion and differentiation is mediated via the sphingolipid pathway: a therapeutic target for Darier's disease. J Invest Dermatol. 2012 Apr; 132(4):1188-95.
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4. Kim H, Kim J, Park J, Kim SH, Uchida Y, Holleran WM, Cho Y. Water extract of gromwell (Lithospermum erythrorhizon) enhances migration of human keratinocytes and dermal fibroblasts with increased lipid synthesis in an in vitro wound scratch model. Skin Pharmacol Physiol. 2012; 25(2):57-64.
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5. Chan A, Holleran WM, Ferguson T, Crumrine D, Goker-Alpan O, Schiffmann R, Tayebi N, Ginns EI, Elias PM, Sidransky E. Skin ultrastructural findings in type 2 Gaucher disease: diagnostic implications. Mol Genet Metab. 2011 Dec; 104(4):631-6.
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6. Park K, Elias PM, Oda Y, Mackenzie D, Mauro T, Holleran WM, Uchida Y. Regulation of cathelicidin antimicrobial peptide expression by an endoplasmic reticulum (ER) stress signaling, vitamin D receptor-independent pathway. J Biol Chem. 2011 Sep 30; 286(39):34121-30.
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7. Rodriguez-Martin M, Martin-Ezquerra G, Man MQ, Hupe M, Youm JK, Mackenzie DS, Cho S, Trullas C, Holleran WM, Radek KA, Elias PM. Expression of epidermal CAMP changes in parallel with permeability barrier status. J Invest Dermatol. 2011 Nov; 131(11):2263-70.
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8. Martin-Ezquerra G, Man MQ, Hupe M, Rodriguez-Martin M, Youm JK, Trullas C, Mackenzie DS, Radek KA, Holleran WM, Elias PM. Psychological stress regulates antimicrobial peptide expression by both glucocorticoid and ß-adrenergic mechanisms. Eur J Dermatol. 2011 May; 21 Suppl 2:48-51.
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9. Glenn DJ, Wang F, Nishimoto M, Cruz MC, Uchida Y, Holleran WM, Zhang Y, Yeghiazarians Y, Gardner DG. A murine model of isolated cardiac steatosis leads to cardiomyopathy. Hypertension. 2011 Feb; 57(2):216-22.
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10. Aburai K, Yoshino S, Sakai K, Sakai H, Abe M, Loiseau N, Holleran W, Uchida Y, Sakamoto K. Physicochemical analysis of liposome membranes consisting of model lipids in the stratum corneum. J Oleo Sci. 2011; 60(4):197-202.
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11. Uchida Y, Houben E, Park K, Douangpanya S, Lee YM, Wu BX, Hannun YA, Radin NS, Elias PM, Holleran WM. Hydrolytic pathway protects against ceramide-induced apoptosis in keratinocytes exposed to UVB. J Invest Dermatol. 2010 Oct; 130(10):2472-80.
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12. Uchida Y, Cho Y, Moradian S, Kim J, Nakajima K, Crumrine D, Park K, Ujihara M, Akiyama M, Shimizu H, Holleran WM, Sano S, Elias PM. Neutral lipid storage leads to acylceramide deficiency, likely contributing to the pathogenesis of Dorfman-Chanarin syndrome. J Invest Dermatol. 2010 Oct; 130(10):2497-9.
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13. Hatano Y, Man MQ, Uchida Y, Crumrine D, Mauro TM, Feingold KR, Elias PM, Holleran WM. Murine atopic dermatitis responds to peroxisome proliferator-activated receptors alpha and beta/delta (but not gamma) and liver X receptor activators. J Allergy Clin Immunol. 2010 Jan; 125(1):160-9.e1-5.
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14. Jiang YJ, Uchida Y, Lu B, Kim P, Mao C, Akiyama M, Elias PM, Holleran WM, Grunfeld C, Feingold KR. Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes. J Biol Chem. 2009 Jul 10; 284(28):18942-52.
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15. Hatano Y, Man MQ, Uchida Y, Crumrine D, Scharschmidt TC, Kim EG, Mauro TM, Feingold KR, Elias PM, Holleran WM. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis. J Invest Dermatol. 2009 Jul; 129(7):1824-35.
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16. Charruyer A, Bell SM, Kawano M, Douangpanya S, Yen TY, Macher BA, Kumagai K, Hanada K, Holleran WM, Uchida Y. Decreased ceramide transport protein (CERT) function alters sphingomyelin production following UVB irradiation. J Biol Chem. 2008 Jun 13; 283(24):16682-92.
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17. Uchida Y, Holleran WM, Elias PM. On the effects of topical synthetic pseudoceramides: comparison of possible keratinocyte toxicities provoked by the pseudoceramides, PC104 and BIO391, and natural ceramides. J Dermatol Sci. 2008 Jul; 51(1):37-43.
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18. Uchida Y, Holleran WM. Omega-O-acylceramide, a lipid essential for mammalian survival. J Dermatol Sci. 2008 Aug; 51(2):77-87.
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19. Elias PM, Williams ML, Holleran WM, Jiang YJ, Schmuth M. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. J Lipid Res. 2008 Apr; 49(4):697-714.
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20. Liu YY, Yu JY, Yin D, Patwardhan GA, Gupta V, Hirabayashi Y, Holleran WM, Giuliano AE, Jazwinski SM, Gouaze-Andersson V, Consoli DP, Cabot MC. A role for ceramide in driving cancer cell resistance to doxorubicin. FASEB J. 2008 Jul; 22(7):2541-51.
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