PART I: General Information Name: Edward V. Maytin Office Address: Department of Dermatology Desk A61, Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland, OH 44195 Email: maytine@bme.ri.ccf.org FAX: (216) 444-9198 Place of Birth: Pullman, Washington, U.S.A. Education: 1978 B.S. Clarkson University (Chemistry) 1984 Ph.D. University of Rochester (Biophysics) 1985 M.D. University of Rochester School of Medicine and Dentistry Postdoctoral Training: Internship and Residencies: 1985-1986 Intern in Medicine, Roger Williams Hospital, Brown University Providence RI 1987-1990 Resident in Dermatology, Harvard Medical School, Boston Clinical and Research Fellowships: 1986-1987 Clinical and Research Fellow (Dermatology), Harvard Medical School 1993-1999 Research Fellow in Medicine (Endocrinology), Howard Hughes Medical Institute, Massachusetts General Hospital Licensure and Certification: 1986 Diplomate of the National Board of Medical Examiners 1986 Full Medical Licensure, Commonwealth of Massachusetts 1990 Full Medical Licensure, State of California 1990 Diplomate of the American Board of Dermatology 2000 Full Medical Licensure, State of Ohio Academic and Hospital Appointments: 1990-1995 Instructor of Dermatology, Harvard Medical School 1996-1999 Assistant Professor of Dermatology, Harvard Medical School 1990-1999 Assistant in Dermatology, Massachusetts General Hospital 1993-1999 Assistant in Molecular Endocrinology (Medicine), MGH 2000-present Full Staff in Dermatology, Cleveland Clinic Foundation 2000-present Assistant Staff in Biomedical Engineering, Cleveland Clinic Foundation Major Committee Assignments: Harvard Medical School: 1990-1996 Residency Selection Committee, Department of Dermatology Massachusetts General Hospital: 1989-1993 Central Planning Committee, Cutaneous Biology Research Center 1990-1996 Scientific Advisory Council, Mallinckrodt Center(GCRC) 1999- Subcommittee on Research Animal Care (SRAC) Professional Societies: 1986-2001 American Medical Association 1990-2001 American Academy of Dermatology 1990-2001 Society of Investigative Dermatology Principal Clinical and Hospital Service Responsibilities: 1990-1999 Dermatology Associates Faculty Practice, MGH 1990-1999 Attending Physician (On-call rotation, Consult Service), MGH 2000-2001 Staff Physician, Dermatology, Cleveland Clinic Foundation Part II: Research, Teaching, and Clinical Contributions A. Narrative report Since my relocation from Harvard to the Cleveland Clinic Foundation in January 2000, I have placed the bulk of my effort (80%) towards advancing a basic-research program on transcription factors of the skin. The work was initiated in 1995 under an NIH Clinical Investigator Award while at MGH in Boston. Based upon that preliminary work, which established the importance of C/EBP transcription factors in the epidermal differentiation program of mammalian skin (Maytin & Habener, J. Invest. Dermatol., 1998), I was funded with an R29 FIRST Award to the NIH (C/EBP? and CHOP in Epidermal Differentiation); this funding has now been transferred to CCF, and will provide research funding through the year 2003. The overall theme of my research program is to delineate the role of C/EBP transcription factors in epidermal differentiation in cutaneous responses to injury, and in therapies of skin disease. Ongoing project areas within my program are as follows: Project 1: C/EBP transcription factors in the regulation of epidermal differentiation. Project 2: Transcription factor CHOP as an inducer of apoptosis. Project 3: UV light-mediated degradation and induction of C/EBPs in the epidermis. Project 4: C/EBP? in the hyperproliferative epidermal response to topical retinoids. Project 5: C/EBPs as therapeutic-response modifiers in photodynamic therapy (PDT) of tumors and skin diseases: (with Bernhard Ortel, coinvestigator). The remaining 20% of my effort is spent in clinical activity within the Department of Dermatology, and as Head of the Section on Molecular Dermatology. I see patients in the Dermatology Access Clinic two days a week. I also participate in teaching activities for the Dermatology Fellows. B. Funding Information (Research) (Dates, Agency, Title, PI/Co-PI, Direct Costs, Title of Grant:) 1990-1991 Dermatology Foundation Grant (PI) $10,000 "Proteins induced by ultraviolet light or heat shock in keratinocytes" 1990-1993 Cutaneous Biology Research Center (PI) (intramural support) "Stress responses to heat shock and ultraviolet light in keratinocytes" 1994-1995 American Cancer Society, MGH IRG (PI) $20,000 "Role of a putative tumor-suppressor gene product, CHOP-10, in the regulation of apoptosis" 1995-1998 NIH Clinical Investigator Award (K08) (PI) $210,000 "Regulation of the K10 gene by C/EBPs in keratinocytes" 1998-2003 NIH First Independent Research Support and Transition Award, "FIRST" (R29) (PI) $350,000 "C/EBP? and CHOP in Epidermal Differentiation" 2000-2001 Cleveland Clinic Foundation/Lerner Research Institute, Bridge Program funding, 2 yr (PI) $200,000 C. Report of Current Research Activities "C/EBP? and CHOP in Epidermal Differentiation", Principal Investigator. (see Narrative above for details) D. Report of Teaching D1. Local Contributions Harvard Medical School: 1990-1993 HMS Ambulatory Care Clerkship, dermatology preceptor to medical students on rotation 1990-1999 Supervised a total of seven undergraduate and medical students on separate three-month laboratory rotations Massachusetts General Hospital: 1990-1999 Dermatology Grand Rounds (leader in rotation with staff) Cleveland Clinic Foundation: 2000- Established a Dermatology Research Fellowship, starting July 1, 2000 2000 "Overview of adhesion molecules in dermatology" Resident teaching session, April 2000 D2. Regional, national, and international contributions 1996 "C/EBP transcription factors in epidermal keratinodytes of the skin are modulated during normal differentiation and by cellular stress" Invited speaker: 12th International Congress of Photobiology Vienna, Austria, September 1-6, 1996. 1997 "Transcription factors in epidermal differentiation: making it to the top" Invited speaker: University of Massachusetts Dept. of Dermatology, Quinsigamond Dermatological Society; October 27, 1997 1998 "Differentiation-specific regulation of the keratin K10 gene is mediated by C/EBP-family transcription factors in the skin." Invited Speaker, Symposium on 'Keratinization and its Disorders, A Molecular Perspective'; Kloster Walberberg, Bornheim, Germany; May 3-5th, 1998. 1998 "The transcription factor C/EBP? directs the expression of the keratin K10 gene in differentiating murine keratinocytes" Oral presentation: International Investigative Dermatology meeting, Cologne, Germany. May 7-10, 1998. 1999 "Direct and indirect roles for transcription factors C/EBP and AP-2 in the regulation of keratin10 gene expression in mammalian epidermis" Oral presentation: Society of Investigative Dermatology meeting, Chicago, IL. May 5-9, 1999. 2000 "Induction of apoptosis by CHOP/gadd153, a transcription factor involved" in carcinogenesis and adaptation to stress" Oral presentation: Society of Investigative Dermatology meeting, Chicago, IL. May 10-14, 2000. 2000 "Transcriptional regulation of epidermal differentiation" Oral presentation: Lerner Research Institute Scientific Retreat, Salt Fork Resort, OH. Sept 5-6, 2000. 2000 "Studying the skin through thick and thin; transcription factors which regulate epidermal differentiation" Visiting Professor, Case Western Reserve Univ., Dept. of Dermatology Cleveland, OH. Dec. 12, 2000. E. Report of Clinical Activities I care for patients as a member of the Dermatology Staff within the setting of a teaching hospital (Cleveland Clinic Foundation). I see general dermatology patients twice a week at CCF with the residents. PART III: Bibliography Original Articles: 1. Maytin EV and Young DA. Separate glucocorticoid, heavy metal, and heat shock domains in thymic lymphocytes. J Biol Chem 1983; 258:12718-12722. 2. Young DA, Voris BP, Maytin EV, Colbert RA. Very-high-resolution two-dimensional electrophoretic separation of proteins on giant gels. Methods Enzymol 1983; 91:190-214. 3. Maytin EV, Balduzzi PC, Notter M, Young DA. "Changes in the synthesis and phosphorylation of cellular proteins in chick fibroblasts transformed by two avian sarcoma viruses. J Biol Chem 1984; 259:12135-12143. 4. Maytin EV, Colbert RA, Young DA. Early heat shock proteins in primary thymocytes: Evidence for transcriptional and translational regulation. J Biol Chem 1985; 260:2384-2392. 5 Levenson RM, Maytin EV, Young DA. Inexpensive microcomputer-based 2-D gel densitometry. Analyt Biochem 1986; 158:294-301. 6. Levenson RM, Maytin EV, Young DA. A novel inexpensive method for 2-D gel densitometry. BioTechniques 1987; 5:298-302. 7. Maytin EV, Wimberly J, Anderson RR. Thermotolerance and the heat shock response in normal human keratinocytes. J Invest Dermatol 1990; 95:635-642. 8. Maytin EV, Levin E, Anderson RR. A laser densitometer for selected spot analysis on two- dimensional dot blots and autoradiograms. Analyt Biochem 1991; 194:284-294. 9. Maytin EV. Differential effects of heat shock and UVB light upon stress protein expression in epidermal keratinocytes. J Biol Chem 1992; 267: 23189-23196. 10. Maytin EV, Murphy LA, Merrill MA. Hyperthermia induces resistance to ultraviolet light (UVB) in primary and immortalized epidermal keratinocytes. Cancer Research 1993; 53:4952-4959. 11. Maytin EV, Wimberly JM, Kane KS. Heat shock modulates UVB-induced cell death in human epidermal keratinocytes: evidence for a hyperthermia-inducible protective response. J Invest Dermatol 1994; 103: 547-553. 12. Kane KS and Maytin EV. Ultraviolet B-induced apoptosis of keratinocytes in murine skin is reduced by mild local hyperthermia. J Invest Dermatol 1995; 104: 62-67. 13. Maytin EV and Habener JF. Transcription factors C/EBP?, C/EBP?, and CHOP (gadd153) expressed during the differentiation program of keratinocytes in vitro and in vivo. J Invest Dermatol 1998; 110: 238-246. 14. Ortel B, Chen N, Brissette J, Dotto GP, Maytin E, Hasan T. Differentiation-specific stimulation of ALA-induced PPIX formation in keratinocytes. Br J Cancer 1998; 77:1744-51. 15. Maytin EV, Lin JC, Krishnamurthy R, Batchvarova N, Ron D, Mitchell PJ, and Habener JF. Keratin 10 gene expression during differentiation of mouse epidermis requires transcription factors C/EBP and AP-2. Dev Biol 1999; 216: 164-181. Proceedings of Meetings 16. Maytin, EV. C/EBP transcription factors in epidermal keratinocytes are modulated during normal differentiation and in response to cellular stress. In: Honigsmann H, Knobler RM, Trautinger F, Jori G, editors. Proceedings of the 12th International Congress on Photobiology; 1996 Sep 1-6; Vienna, Austria. Milan: OEMF; 1998. p. 267-271. Reviews, Chapters, and Editorials 17. Maytin EV. Basic life sciences, vol 53, DNA damage and repair in human tissues Arch Dermatol 1991; 127:1089-1090. [book review]. 18. Maytin EV. Clinical Photomedicine J Am Acad Dermatol 1994; 31:143. [book review]. 19. Maytin EV. Heat shock proteins and molecular chaperones: implications for adaptive responses in the skin. J Invest Dermatol 1995; 104: 448-455. [invited scientific review] 20. Romero RA and Maytin EV. Keratins and their role in epidermal diseases. Dermatol Cosmet (Llorca MA, ed., Madrid) 1997; VII: 207-213. [invited scientific review] Clinical Communications 21. Maytin EV, Levine JR, Dover JS. Life-threatening hemorrhage from a 4-mm punch biopsy site in a patient with AIDS and hemophilia A. J Am Acad Dermatol 1989; 21:1033-1034. 22. Maytin EV, Horan RF, Dover JS. Tumorous nodules on the lower extremities. Arch Dermatol 1991; 127: 405-410. [case report on mastocytosis]. 23. Maytin EV. Reactions to heat and cold. In: Olbricht SM, Bigby ME, Arndt KA, eds. Manual of Clinical Problems in Dermatology. Boston: Little, Brown, and Co., 1992: 206-211. 24. Maytin EV. Cutaneous signs of internal malignancy. In: Olbricht SM, Bigby ME, Arndt KA, eds. Manual of Clinical Problems in Dermatology. Boston: Little, Brown, and Co., 1992: 272-277. 25. Maytin EV. Warts. In: Olbricht SM, Bigby ME, Arndt KA, eds. Manual of Clinical Problems in Dermatology. Boston: Little, Brown, and Co., 1992: 149-153. 26. Maytin EV. Contact dermatitis. In: Olbricht SM, Bigby ME, Arndt KA, eds. Manual of Clinical Problems in Dermatology. Boston: Little, Brown, and Co., 1992: 250-256. Thesis 27. Maytin EV. Gene expression after glucocorticoids, viral infection, and heat shock in thymic lymphocytes [dissertation]. Rochester (NY): University of Rochester; 1985. Abstracts (recent): 28. Romero RA, Gonzalez S, and Maytin EV. Transcription factor C/EBP? in rhino mouse epidermis is upregulated by retinol but not retinoic acid . J Invest Dermatol 1998; 110: 607. 29. Hamblin MR, Miller JL, Rizvi I, Ortel B, Maytin EV, and Hasan T. Mechanism of differential phototoxicity after pegylation of poly-l-lysine chlorin e6 conjugates. American Society for Photobiology, Snowbird, UT; 1998: Photochem. Photobiol. 1998; 67: 24S. 30. Rizvi R, Hamblin M, Miller J, Ortel B, Maytin EV, Hasan T. Selective Targeting of Intraperitoneal Tumors. 7th Biennial Congress of the International Photodynamic Association, Nantes, France, July 1998. 31. Maytin EV, Lin JC, Ron D, Habener JF. Differentiation-specific regulation of the keratin k10 gene is mediated by C/EBP and AP-2 family transcription factors in the skin. International Symposium on Keratinization and its Disorders: A Molecular Perspective, Kloster Walberberg, Germany, May 1998 32. Maytin EV, Lin JC, Habener, JF. The transcription factor C/EBP? directs the expression of the keratin K10 gene in differentiating murine keratinocytes. J Invest Dermatol 1998; 110: 493. 33. Torres R, Gonzalez S, Maytin EV. Loss and induction of transcription factors C/EBP? and CHOP (gadd153) in murine epidermis following exposure to UVB light. J Invest Dermatol 1999; 112: 612. 34. Maytin EV, Lin JC, Krishnamurthy R, Batchvarova N, Ron D, Mitchell PJ, and Habener JF. Direct and indirect roles for transcription factors C/EBP and AP-2 in the regulation of keratin10 gene expression in mammalian epidermis. J Invest Dermatol 1999; 112: 530. 35. Maytin EV, Ubeda M, Lin JC, Habener JF. Induction of apoptosis by CHOP/gadd153, a transcription factor involved in carcinogenesis and adaptation to stress. J Invest Dermatol 2000; 114: 763. (CV in HMS format; prepared 1/10/2001 ) Edward V. Maytin, page 3 Curriculum Vitae for Edward V. Maytin, page 1