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homas Jefferson University, Philadelphia.

• 2) Laboratory Teaching Associate of Molecular Diagnostic Techniques (Graduate and Undergrad. – Bioscience Technologies: Medical Technology) College of Health Professions, Thomas Jefferson University, Philadelphia.

• 3) Italian teacher at the America-Italy Society.
Professional Development Certificate: Teaching Italian in a learned-centered approach. University of Pennsylvania, Philadelphia.







RESEARCH EXPERIENCE

2007-2008: Research Associate with Dr. Teresa Alnemri – Assistant Professor,
Department of Biochemistry and Molecular Biology,
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia.
Accomplishments:
 1) Established new conditions and protocols for intercrossing and genotyping animals in a mouse model for human inflammatory disease to validate biochemical pathway leading to caspase-1 activation in these phenotypes.

2005 – 2007: Research Associate with Dr. L. Siracusa – Associate Professor,
Department of Microbiology and Immunology,
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia.
Accomplishments:
• 1) Studied the potential role of microRNAs as cancer modifier genes in mouse strains with different tumor susceptibility.
• 2) Published review entitled “Mammalian microRNAs: a small world for fine-tuning gene expression” in Mammalian Genome (Sevignani et al. 2006).
• 3) Development of new microsatellites markers to identify chromosomal regions carrying potential new modifier genes in a mouse model for intestinal cancer.

2000 - 2005: Research Instructor with Dr. C. Croce – Director, Kimmel Cancer Center,
Department of Microbiology and Immunology,
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia.
Accomplishments:
• 1) MicroRNAs involvement in human cancers on a genome-wide basis was investigated mapping 186 microRNAs and comparing their location to previously reported nonrandom genetic alterations. This was the first report showing that human microRNA genes are frequently located in cancer associated regions (Calin & Sevignani et al. 2004). Contributed to development of a customized microarray to study microRNA genes expression (Liu et al. 2004).
• 2) The potential of TES gene therapy was studied by evaluating the effects of adenoviral TES transduction (Ad-TES) in cell lines, confocal imaging system was used to monitor the infection rate (Sarti & Sevignani et al. 2005).

1999 - 2000: Post-Doctoral fellowship with Dr. Andrei Thomas-Tikhonenko.
Department of Pathobiology, Veterinary School,
University of Pennsylvania, Philadelphia.
Accomplishments:
• 1) In order to identify gene involved in cell proliferation, gene expression profiles were compared in p53-deficient murine colonocytes and their c-Myc-transformed counterparts, which possess enhanced proliferative potential (Tikhonenko et al. 2004).
• 2) Ectopic and/or orthotopic transplantation of murine colonocytes were done in immunocompetent syngeneic hosts (Dews et al. 2006).

1996 - 1998: Post-Doctoral fellowship with Dr. Bruno Calabretta.
Department of Microbiology and Immunology,
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia.
Accomplishments:
• 1) Established primary cultures of epithelial cells from the colonic crypts of p53-deficient mice. This was the first attempt that successfully established a long term primary culture from mouse colonic crypts. After ectopic expression of an activated Ki-ras these cells acquire a tumorigenic phenotype as shown by forming colonies in soft agar and growing as tumors in immunodeficient SCID mice and in immunocompetent syngeneic hosts (Sevignani et al. 1998).
• 2) Established primary cultures of epithelial cells from the colon crypts of Msh2-/- p53-/- double-knockout mice. These cells undergo spontaneous transformation. Treatment of early passage cells with the mutagen methylmethane thiosulfonate (MMS) further decreases the transformation latency (Sevignani et al. 1999).

1992 - 1995: Thesis in the Laboratory of Cell Biology, with Dr. Alberto Giannetti.
Department of Dermatology, University of Modena (Italy).
• Responsibilities: Evaluating ECP (eosinophilic cationic protein) serum levels and immunohistoistochemistry (anti-EG1 and anti-EG2 monoclonal antibodies) of skin biopsy in patients affected by chronic idiopathic urticaria.




1990 - 1992: Fellowship with Dr. Alberto Giannetti, Laboratory of Cell Biology,
Department of Dermatology, University of Modena (Italy).
• Responsibilities: Primary culture of keratinocytes derived from human skin. Immunohistochemistry and Flow Cytometry to study the expression of neuropetides in human skin.

1988 - 1990: Fellowship with Dr. Antonino Forabosco, Laboratory of Cytogenetics,
Department of Human Anatomy, University of Modena (Italy).
• Responsibilities: Primary cell cultures derived from different kinds of solid tissues,
amniotic liquid, blood and kariotyping (screening of inherited chromosomal
abnormalities).

1987 - 1988: Internship with Dr. Gianpaolo Trentini, Laboratory of Human Pathology,
Department of Anatomy and Pathology, University of Modena (Italy).
• Responsibilities: Cytology, Electron Microscopy, Flow Cytometry, Immunochemistry
and Histology.

EDUCATION

2001 - 2002: Non-degree Pre-MBA program at Thomas Jefferson University, Philadelphia
(1. Management, 2. Macroeconomics - Prof. W. Sudell).

1995 - 1999: Specialty in Clinical Pathology (Post Graduate Certif. - 4 years). Earned in 1999.
Program of the 1st year: Molecular Diagnostics, 2nd year: Gene Therapy,
3rd year: Cancer Genetics, 4th year: Virology. Department of Pathology, University of Modena (Italy).

1996: Earned Research Doctorate (Ph.D.) in Dermatological Immunology.
1992 - 1995: Ph.D. program in Dermatological Immunology, Department of Dermatology,
Laboratory of Cell Biology, University of Modena (Italy).

1990: Graduated in Natural Sciences (MS), University of Modena (Italy).

1987: Graduated in Biology (MS), University of Modena (Italy).

1976 - 1981: The Art Institute of Trento – Visual Arts (Italy).

TECHNICAL BACKGROUND

MOLECULAR BIOLOGY:
In situ Hybridization (ISH).
Radiolabeling of oligo-probes.
Nucleic acid isolation, Southern Blot.
Ribonucleic acid isolation, Northern Blot and RNase protection assay.
PCR, RT-PCR.
RDA (Representational difference analysis), cDNA differential gene expression array.
Cloning, Plasmid construct and prep.
Cell transfection: electroporation, lipofection and retroviral infection.
Immunoenzymaticassay (E.L.I.S.A.).
Radioimmunoassay (R.I.A.-R.I.B.A.).
Protein isolation, immunoprecipitation, Western Blot.

CELL BIOLOGY:
Primary Cell Cultures: murine colonocytes from colonic crypts, human keratinocytes, fibroblasts, amniotic liquid, hematopoietic cells.
Flow Cytometry.
Clonogenic assays.
Tumorigenic assay in vitro: soft agar.
Tumorigenic assay in vivo: S.C. and I.P. injection in animal model.
Mouse models of Cancer: ectopic and/or orthotopic transplantation in mouse model (intraspleenic and intracecal injections) and microsurgery.
Laser Capture Microdissection (LCM).
DIAGNOSTIC EXPERIENCE:
Cytology and cytodiagnosis (cervix smear-test).
Histology: practical skills in basic techniques, frozen sections and paraffin embedded tissues.
Immunohistochemistry.
Electron Microscopy: complete preparation of samples.
Cytogenetics: screening of inherited chromosomal abnormalities.

GRAPHICS SKILLS:
Computer Graphics, Painting, Drawing, Cartoons.

PERSONAL SKILLS:

1. Team-oriented
2. Good teaching skills
3. Flexibility
4. Ability to work effectively with diverse groups
5. Creativity
6. Good organizational skills
7. Critical thinking skills
8. Good communication skills
9. Good planning



PUBLICATIONS


1. F. Rivasi, G. De Aloysio, R.A. Fano, F. Boselli, C. Sevignani: Use of avidin-biotin-peroxidase complex (A.B.C.) technique for the localization of Human Papilloma Virus on semithin sections of cytologic cervico-vaginal samples embedded by electron microscopy. The CERVIX and the lower female genital tract 8: 349-354, 1990.

2. C. Kirchlechner, C. Sevignani, M. Bondi: Investigation of pollution in Caldaro Lake (Italy). L'Igiene Moderna 94: 55-67, 1990.

3. M. Bondi, C. Grisolia, C. Sevignani, M. Migaldi: "Farmer's lung" as a professional disease in agriculture: environmental investigation. Riv. Tuberc. Mal. App. Resp. 22: 299-316, 1990.

4. C. Pincelli, F. Fantini, A. Baraldi, C. Sevignani, A. Spattini, A. Giannetti: Neurochemical markers in skin from patients with uremic pruritus. E.S.D.R. Annual Meeting , Turin June 9-12, 1990. J Invest Dermatol 95: 483, 1990


5. F. Fantini, C. Pincelli, C. Sevignani, A. Baraldi, A. Giannetti: Langerhans cells can express neuron-specyfic enolase (N.S.E.) immunoreactivity. Arch Dermatol Res 283: 10-12, 1991

6. C. Pincelli, F. Fantini, L. Benassi, C. Sevignani, A. Giannetti: Effects of vasoactive intestinal polipeptide-related peptides on the proliferation of cultured human keratinocytes. J Invest Dermatol 96: 558, 1991

7. F. Fantini, A. Baraldi, C. Sevignani, A. Spattini, C. Pincelli, A. Giannetti: Cutaneous innervation in chronic renal failture patients. An immunohistochemical study. Acta Derm-Venereol 72: 102-105, 1992

8. C. Pincelli, F. Fantini, C. Sevignani, L. Benassi, A. Giannetti: Substance P inhibits the vasoactive intestinal polypeptide (VIP)-induced proliferation of cultured human keratinocytes. J Invest Dermatol 98: 538, 1992

9. C. Pincelli, F. Fantini, P. Romualdi, G. Lesa, C. Sevignani, A. Giannetti: Substance P and Vasoactive Intestinal Polypeptide in pathogenesis of psoriatic lesions. Neuropeptides 22,1: 52-53, 1992

10. C. Pincelli, F. Fantini, C. Sevignani, A. Baraldi, A. Giannetti: Cutaneous innervation in chronic renal failture patients. An immunohistochemical. Chronica Dermatologica (Suppl) Gennaio-Febbraio: 43-44, 1992

11. C. Pincelli, F. Fantini, P. Romualdi, C. Sevignani, G. Lesa, L. Benassi, A. Giannetti: Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes. J Invest Dermatol 98: 421-427, 1992

12. C. Pincelli, F. Fantini, L. Giardino, M. Zanni, L. Calzà, C. Sevignani, A. Giannetti: Autoradiographic detection of substance P receptors in normal and psoriatic skin. J Invest Dermatol 101: 301-304, 1993

13. C. Pincelli, C. Sevignani, A. Grande, F. Fantini, L. Aloe, A. Giannetti: Normal human keratinocytes express nerve growth factor receptor and proliferate in response to nerve growth factor. J Invest Dermatol 100: 439A, 1993

14. C. Pincelli, C. Sevignani, R. Manfredini, A. Grande, F. Fantini, L. Bracci-Laudiero, L. Aloe, S. Ferrari, A. Cossarizza, A. Giannetti: Expression and function of Nerve Growth Factor and nerve growth factor receptor on cultured keratinocytes. J Invest Dermatol 103: 13-18, 1994

15. A.Motolese, C. Sevignani, A. T. Scacchetti, B. M. Manzini, M. Donini: Levels of eosinophilic cationic protein (ECP) in the serum of patients pazienti affected by chronic idiopathic urticaria. G Ital Dermatol Venereol 131: 83-7, 1996

16. P. Wlodarski, M. Wasik, M. Ratajczak, C. Sevignani, G. Hoser, J. Kawiak, B. Calabretta, T. Skorski: Role of p53 in hematopoietic recovery after cytotoxic treatment. Blood 91: 2998-3006, 1998

17. C. Sevignani, P. Wlodarski, J. Kirillova, K. G. Danielson, E. W. Mercer, R. V. Iozzo, B. Calabretta: Tumorigenic conversion of p53-deficient colon epithelial cells by an activated Ki-ras gene. J Clin Invest 101: 1572-1580, 1998

18. C. Sevignani, A. Craston, R. Fishel, R.V. Iozzo, B. Calabretta: Spontaneous and mutagen-induced transformation of primary cultures of p53-/-Msh2-/- colonocytes. Cancer Res 59: 5882-5886, 1999 – U.S. Provisional Patent Application entitled: Culture of Msh2-/-p53-/- Colonocytes as in Vitro Cancer Model. Ref.No.: CAL01.P0001 Filed: November 30, 1999

19. M. Cervellera, G. Raschella, G. Santilli, B. Tanno, A. Ventura, C. Mancini, C. Sevignani, B.Calabretta, A. Sala: Expression of Apolipoprotein J gene (Clusterin) is positively regulated by B-Myb in neuroblastoma cells and correlates with advanced disease stages. J Biol Chem Apr 18, 2000

20. A. Janz, C. Sevignani, K. Kenyon, C. Ngo, A.T. Tikhonenko: Activation of Myc oncoprotein leads to increased turnover of thrombospondin-1 mRNA. Nucleic Acids Research 28 (11): 2268-2275, 2000

21. C. Hunter, D. Yu, M. Gee, C. Ngo, C. Sevignani, M. Goldschmidt, T. Golovkina, S. Evans, W.M. Lee, A.T. Tikhonenko: Systemic inhibition of angiogenesis underlies resistance to tumors during acute toxoplasmosis. J Immunol. 2001 May 15; 166 (10): 5878-81
22. B.Turner, M. Ottey, D. B. Zimonjic, M. Potoczek, W. W. Hauck, E. Pequignot, C. Keck-Waggoner, C. Sevignani, M. Aldaz, P. McCue, J. Palazzo, K. Huebner, N. C. Popescu. The FHIT/FRA3B locus and repair deficient cancers. Cancer Res. July 15; 62 (14), 2002

23. Sevignani C, Calin GA, Cesari R, Sarti M, Ishii H, Yendamuri S, Vecchione A, Trapasso F, Croce CM. Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in breast cancer cell lines. Cancer Res. 2003 Mar 15;63(6):1183-7

24. *Calin GA, *Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999-3004. Epub 2004 Feb18 (*Calin GA and *Sevignani C contributed equally to this work)

25. Thomas-Tikhonenko A, Viard-Leveugle I, Dews M, Wehrli P, Sevignani C, Yu D, Ricci S, el-Deiry W, Aronow B, Kaya G, Saurat JH, French LE. Myc-transformed epithelial cells down-regulate clusterin, which inhibits their growth in vitro and carcinogenesis in vivo. Cancer Res. 2004 May 1;64(9):3126-36

26. Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9740-4. Epub 2004 Jun 21. - (Patent Application)

27. Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell'Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A. 2004 Jul 29 [Epub ahead of print]

28. Vecchione A, Sevignani C, Giarnieri E, Zanesi N, Ishii H, Cesari R, Fong LY, Gomella LG, Croce CM, Baffa R. Inactivation of the FHIT gene favors bladder cancer development. Clin Cancer Res. 2004 Nov 15;10(22):7607-12

29. *Sarti M, *Sevignani C, Calin GA, Aqeilan R, Shimizu M, Pentimalli F, Picchio MC, Godwin A, Rosenberg A, Drusco A, Negrini M, Croce CM. Adenoviral Transduction of TESTIN Gene into Breast and Uterine Cancer Cell Lines Promotes Apoptosis and Tumor Reduction In vivo. Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):806-13. (*Sarti M and *Sevignani C contributed equally to this work)

30. *Zanesi N, *Mancini R, *Sevignani C, Vecchione A, Kaou M, Valtieri M, Calin GA, Pekarsky Y, Gnarra JR, Croce CM, Huebner K. Lung cancer susceptibility in Fhit-deficient mice is increased by Vhl haploinsufficiency. Cancer Res. 2005 Aug 1;65(15):6576-82 (*N. Zanesi, *R. Mancini, and *C. Sevignani contributed equally to this work)

31. Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005 Oct 27;353(17):1793-801

32. Zanesi N, Aqeilan R, Drusco A, Kaou M, Sevignani C, Costinean S, Bortesi L, La Rocca G, Koldovsky P, Volinia S, Mancini R, Calin G, Scott CP, Pekarsky Y, Croce CM. Effect of rapamycin on mouse chronic lymphocytic leukemia and the development of nonhematopoietic malignancies in Emu-TCL1 transgenic mice. Cancer Res. 2006 Jan 15;66(2):915-20

33. Sevignani C, Calin GA, Siracusa LD, Croce CM. Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome. 2006 Mar; 17(3):189-202. Epub 2006 Mar 3

34. M.Dews, A.Homayouni, D.Yu, D.Murphy, C. Sevignani, E.Wentzel, E.E.Furth, W.M. Lee, G.Enders, J.Mendell, and A.Thomas-Tikhonenko. "Augmentation of tumor angiogenesis by the Myc-activated microRNA cluster", Nature Genetics. 2006 38(9):1060-1065

35. Wlodarski P, Sevignani C, Fernandes MJ, Calabretta B, Wlodarski KH. Tumor induced by Moloney sarcoma virus causes periosteal osteogenesis engaging osteopontin, fibronectin, stromelysin-1 and tenascin. Neoplasma. 2007; 54(2):173-9

36. *Sevignani C, *Calin GA, Nnadi S, Shimizu M, Davaluri RV, Hyslop T, Demant P, Croce CM, Siracusa L. MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci USA 2007 May 8; 104(19):017-8022. (*Sevignani C and *Calin GA contributed equally to this work)

37. Yendamuri S, Trapasso F, Ferracin M, Cesari R, Sevignani C, Shimizu M, Rattan S, Kuroki T, Dumon KR, Bullrich F, Liu CG, Negrini M, Williams NN, Kaiser LR, Croce CM, Calin GA. Tumor suppressor functions of ARLTS1 in lung cancers. Cancer Res. 2007 Aug 15;67(16):7738-45

38. Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C, Fabbri M, Cimmino A, Lee EJ, Wojcik SE, Shimizu M, Tili E, Rossi S, Taccioli C, Pichiorri F, Liu X, Zupo S, Herlea V, Gramantieri L, Lanza G, Alder H, Rassenti L, Volinia S, Schmittgen TD, Kipps TJ, Negrini M, Croce CM. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007 Sep;12(3):215-29

39. Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P, Sevignani C, Byrne D, Negrini M, Pagano F, Gomella LG, Croce CM, Baffa R. Micro-RNA profiling in kidney and bladder cancers. Urol Oncol. 2007 Sep-Oct;25(5):387-92

40. Baffa R, Fassan M, Sevignani C, Vecchione A, Ishii H, Giarnieri E, Iozzo RV, Gomella LG, Croce CM. Fez1/Lzts1 deficient mice are more susceptible to N-butyl-N-(4-hydroxybutil) nitrosamine (BBN) carcinogenesis. Carcinogenesis. 2008 Jan 12 [Epub ahead of print]



INVITED LECTURE
November 3, 1997 – “Tumorigenic conversion of p53-deficient colon epithelial cells by an activated Ki-ras gene”. Department of Oncology, University of Modena (Italy)

MEMBERSHIPS IN PROFESSIONAL AND SCIENTIFIC:
American Association for Cancer Research (member, 2000 – 2005)

COMMUNITY SERVICE:
FAKS – Foster, adoptive and kinship support, Inc. (member, 2004 – 2005)
Philadelphia, PA 19124


Red Cross Volunteer (Modena – Italy: 1990-1995)

Adult CPR and First Aid (American Red Cross: 2003)

Adult CPR (American Heart Association: 2005)


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