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CURRICULUM VITAE Part I General Information DATE PREPARED 09/23/11 Name: Sabina Signoretti, M.D. Office Address: Department of Pathology, Brigham and Women’s Hospital, Thorn 504A 75 Francis Street Boston MA 02115 Ph : 617-525-7437 e-mail: [email protected] Home Address: 77 Wenham Street Apt.2, Jamaica Plain, MA 02130 Work E:Mail: [email protected] Place of birth: Rome, Italy Work FAX: 617-264-5169 Education: 1982-1988 M.D. University of Rome “La Sapienza”, Rome, Italy Postdoctoral Training: Residencies: 1989-1993 Resident in Pathology, University of Rome “La Sapienza” Fellowships: 1995-1996 1996-1997 Research Fellow in Hematopathology, Beth Israel Hospital, Boston, MA Research Fellow in Molecular Pathology, Beth Israel Deaconess Medical Center, Boston MA. Licensure and Certification: 1988 State licensure examination, Italy Academic Appointments: 1996-1997 1999-2003 2003-2008 2009- Research Fellow, Harvard Medical School, Boston, MA Instructor in Pathology, Harvard Medical School Assistant Professor of Pathology, Harvard Medical School Associate Professor of Pathology, Harvard Medical School Hospital Appointments: 1993-1995; 1998 1999-2003 1999- Attending Pathologist, Istituto Dermopatico dell'Immacolata (IDI), Rome, Italy Research Associate, Brigham and Women’s Hospital Associate Pathologist, Dana-Farber Cancer Institute 1 2003200620062011- Associate Pathologist, Brigham and Women’s Hospital Affiliate Faculty, Harvard Stem Cell Institute Member, DFCI/BWH Center for Molecular Oncologic Pathology Visiting Postdoctoral Scholar, Broad Institute of Harvard and MIT Hospital and Health Care Organization Responsabilities: 1993-1995; 1998 1996-1997 1999-2004 2005- Diagnostic Dermatopathology, Istituto Dermopatico dell'Immacolata (IDI), Rome, Italy Supervisor of the Core Molecular Pathology Laboratory at Beth Israel Deaconess Medical Center Associate Pathologist, Prostate Cancer Pathology Core Facility and In situ Hybridization Core Facility, Dana-Farber Harvard Cancer Center (DF/HCC) Associate Pathologist, Specialized Histopathology Core Facility, Dana-Farber Harvard Cancer Center (DF/HCC) Major Administrative Responsibilities: Local 200420082010- Director, Tissue Acquisition Pathology and Clinical Data Core of DF/HCC Kidney Cancer SPORE and Program Director, DF/HCC Tissue Microarray and Imaging (TMI) Core Co-Leader, DF/HCC Kidney Cancer Program Major Committee Assignments: Local 200420042005200520082008200920102011- Member, DF/HCC Kidney Cancer SPORE Governance Committee Co-chair, DF/HCC Kidney Cancer SPORE Specimens & Data Utilization Committee Member, DF/HCC Specialized Histopathology Core Facility User Committee Member, DF/HCC Tissue Microarray Core Facility User Committee Member, DFCI/BWH Center for Molecular Oncologic Pathology Advisory Committee Member, DF/HCC Scientific Council Member, Urologic Disease Working Group of The Cancer Genome Atlas (TCGA) Program (NCI/ NHGRI) Member, NCI Renal Cancer Task Force (RCTF) Kidney Cancer Analysis Working Group of The Cancer Genome Atlas (TCGA) Program (NCI/ NHGRI) Professional Societies (Member): 1999- American association for Cancer Research New England Society of Pathologists US and Canadian Academy of Pathology 2 Grant review activities: 2003 2004- 2005 2006- Scientific Reviewer, Cell Biology Review Panel #1, Department of Defense Prostate Cancer Research Program Scientific Reviewer, Pathobiology Review Panel #3, Department of Defense Prostate Cancer Research Program Scientific Reviewer, Pathobiology Review Panel #2, Department of Defense Prostate Cancer Research Program Community Service Related to Professional Work: 2006; 2010 2007- 2009 Mentor, DF/HCC Continuing Umbrella of Research Experiences (CURE) Program Mentor, Partners Student Success Jobs Program, Brigham and Women’s Hospital Editorial activities: 2004- Ad hoc reviewer: American Journal of Pathology, American Journal of Physiology, Breast Cancer Research, British Journal of Cancer, BJU International, Cancer, Cancer Research, Clinical Cancer Research, Development, Developmental Biology, Diagnostic Molecular Pathology, Human Pathology, International Journal of Cancer, Journal of Urology, Laboratory Investigation, Lancet Oncology, Nature Medicine, PLoS ONE 2008- Member, Editorial Board: Clinical Cancer Research Diagnostic Molecular Pathology Awards and Honors: 1988 1998 2001 2002 2007 Part II M.D, summa cum laude, University of Rome The Daland Award, The New England Cancer Society, Worcester, MA Hershey Young Investigator Award, Boston MA CaP CURE Award Partners in Excellence Award, Student Success Jobs Program Mentor Research, Teaching, and Clinical Contribution A. Narrative Report: Research contributions: My research is focused on genitourinary malignancies, including prostate, bladder and renal cancer. Defining the cell(s) of origin of tumors is fundamental to elucidate the molecular mechanisms involved in their pathogenesis. A major limitation for the identification of the cell type(s) involved in the initiation and propagation of prostate and bladder cancers is that the identity of stem cells and differentiation programs in these epithelia remains unclear. My research aims to identify cell lineages in the prostate and bladder urothelium. I have previously demonstrated that p63 is selectively expressed in basal cells of the prostate and urothelium and that p63-deficient 3 mice present defects in the development of these tissues. My subsequent studies have shown that the early developing prostate (prostate buds) consists exclusively of p63-positive basal cells, which then give rise to secretory cells and thus represent progenitor/stem cells. In contrast, my analysis of the urothelium shows that umbrella (superficial) cells can develop and be maintained independently from p63-positive cells. I am currently utilizing animal models to further characterize the role of p63 in the development and renewal of the prostate and bladder epithelium. This approach is likely to offer new insights in the biology of prostate and bladder development and open new perspectives in the identification of the cell of origin of prostate and bladder carcinoma. An important focus of my research in kidney cancer is the identification of novel oncogenes and tumor suppressor genes. In collaboration with Drs. Kaelin and Beroukhim at DFCI and the Broad Institute, we are currently using an integrated analysis of single-nucleotide polymorphism (SNP) arrays data with matched gene expression data to identify genes targeted by non-random genetic aberrations in RCC. Results from these studies have the potential to identify new drug targets and may eventually lead to new therapeutic approaches for patients with kidney cancer. My laboratory is also very involved in translational research activities. I currently serve as the Director of the Tissue Acquisition, Pathology, and Clinical Data (TAPCD) Core of the DF/HCC Kidney Cancer SPORE and Program. I am also the Director of the DF/HCC Tissue Microaaray and Imaging Core. Teaching contributions: I have been actively involved in teaching since the beginning of my career. I daily teach and tutor post-doctoral fellows and research assistant working in my research laboratory. Moreover, I serve as a Tutor in the Pathology course at Harvard Medical School. Clinical contributions: Throughout my career I have been involved in both patient care and in the development of new tools that could be helpful in the diagnosis and treatment of diseases. As a Research Fellow, I developed a novel PCR-based T-cell clonality assay, which is currently being utilized for the diagnosis of T-cell lymphomas (Signoretti et al., Am J Pathol, 1999 and accompanying editorial). More recently, I demonstrated that p63 is a reliable marker of prostate basal cells that is not expressed in prostate carcinoma. After extensive validation by other groups, p63 immunohistochemistry is currently used in routine clinical practice for the evaluation of challenging prostate biopsies. B. Funded Research Support: Past 1996-1997 1997-1998 2001 Oncor, Inc. Evaluation of the Oncor HER-2/neu (ERBB2) gene amplification detection kit for the interpahse detection of HER-2/neu (ERBB2) genomic sequences in human breast tissue for node-negative primary breast cancer. Multi-institutional study for FDA approval of the HER-2/neu (ERBB2) gene amplification detection kit. (Kit FDA approved Jan 1998). Co-investigator. Ministero della Pubblica Istruzione, Rome, Italy. Detection of B-cell clonality in cutaneous B-cell infiltrates. Co-investigator. Hershey Foundation Award (Signoretti, DFCI). A mouse model for prostate stem cells. Principal Investigator. 4 2001-2004 DOD U.S. Army, CDMRP - New Investigator Award (Signoretti, DFCI). The basal cell marker p63 and prostate stem cells. Principal Investigator. 2002 CaP CURE Foundation Award (Signoretti, DFCI). An animal model for the identification of prostate stem cells. Principal Investigator. 2002-2007 NIH/NCI. Prostate Cancer SPORE / Pathology Core (Kantoff, DFCI). Co-investigator. 2004-2006 NIH/NCI. Kidney Cancer SPORE Developmental Project (Signoretti, BWH). Molecular analysis of renal cell carcinoma using Single Nucleotide Polymorphisms (SNP) arrays. Principal Investigator. 2005-2007 NIH/NIDDK-R21. Defining cell lineages in the bladder urothelium (Signoretti, BWH). Principal Investigator. 2006-2008 NIH/NCI. Kidney Cancer SPORE Developmental Project. Development of mouse orthotopic xenografts of human renal cell carcinoma (Signoretti, BWH). Principal Investigator. 02/08/06-02/07/10 DOD. U.S. Army. CDMRP - Idea Development Award. p63 in development and maintenance of the prostate epithelium (Signoretti, BWH). Principal Investigator. 2007 NIH/NCI. ICBP Pilot Project supported by 5U54 CA112962-03 (Golub, DFCI). Integrating gene expression with high-resolution genetic analysis to identify oncogenic kinases in kidney cancer. Principal Investigator. 01/01/07-12/31/08 Doris Duke Charitable Foundation. Distinguished Clinical Scientist Award (Kaelin, DFCI). Co-investigator. 06/01/07-06/30/09 Harvard Stem Cell Institute. Seed Grant. Identification of Stem Cells In Prostate and Bladder Epithelia (Signoretti, BWH). Principal Investigator. 09/01/09 – 08/31/10 NIH/NCI. of the Kidney Cancer SPORE P50 CA101942 Developmental Project. Clinical, histological and molecular determinants of bilateral renal cell cancer. Principal Investigator. Current Active 04/01/01-03/31/11 05/19/06-11/30/11 05/19/06-11/30/11 06/01/09-05/31/14 NIH/NCI. PO1 CA089021. The Role of PTEN and PI3K Pathway in Prostate Cancer (Cantley, BIDMC). Co-investigator. NIH/NCI. DF/HCC P30 CA06516. Specialized Histopathology Core (Aster, BWH). Co-investigator. NIH/NCI. DF/HCC P30 CA06516. Tissue Microarray and Imaging (TMI) Core (Signoretti, BWH). Principal Investigator. NIH/NCI. Kidney Cancer SPORE P50 CA101942. Tissue Acquisition Pathology and Clinical Data Core (CORE# 3) (Signoretti, BWH). Principal Investigator. 5 06/01/09-05/31/14 NIH/NCI. Kidney Cancer SPORE P50 CA101942. Treatment of VHL-/- clear cell renal carcinoma with HIF2 siRNA (Kaelin DFCI, Choueiri DFCI, Signoretti BWH). Co-Principal Investigator of Project 2. 09/01/10 – 07/31/15 NIH/NIDDK. 1R01DK089975 (Signoretti, BWH). Mechanisms Regulating Prostate Epithelium Maintenance and Regeneration. Principal Investigator. 04/01/11-03/31/15 NIH/NCI. 1R01 CA152330-01 (Seth, BIDMC). Pathway Specific Imaging in VHL Deficient Renal Cancer. Co-investigator. 11/01/11-10/30/15 NIH/NCI. 1R01CA154475-01 (Pedrosa, BIDMC). Non-invasive Physiologic Predictors of Aggressiveness in Renal Cell Carcinoma. Co-investigator. 11/01/11-10/30/12 NIH/NCI. Kidney Cancer SPORE P50 CA101942. Director’s choice Award. Characterization of molecular alterations in metanephric adenoma of the kidney. Principal Investigator. C. Current Research Activities #1: Role of p63 in development and renewal of the prostate and bladder epithelium Unraveling the mechanisms regulating the development and renewal of normal tissues is not only one of the main goals of developmental biology but also an essential step for the elucidation of the mechanisms underlying the development of pathological processes, namely cancer. Although epithelial stem cells have been identified in the skin and intestine, the way the prostate and bladder epithelium are formed and maintained remains unclear. The basal cell marker p63 is selectively expressed in the basal cells of several epithelia, including the prostate and the bladder. My research group has previously demonstrated that p63-deficient (p63-/-) mice present defects in prostate buds and urothelial development (Signoretti et al., Am J Pathol 2000). We have more recently performed in vivo studies utilizing the p63-/- mouse as a tool to define cell lineages in the prostate epithelium and urothelium. Results from these studies show that when developmental defects of p63-/- embryos are abolished by injecting p63+/+ ES cells into 3.5dpc p63-/- blastocysts, only p63+/+ cells compose the normal prostate epithelium of 7-weeks old chimeric mice. These findings indicate that prostate secretory cells of young adult mice derive from p63-positive progenitor cells that constitute the prostate buds. Surprisingly, in contrast with the prostate findings, analysis of the urothelium of the rescued p63-/- chimeras demonstrates that urothelial umbrella cells can develop independently from p63-positive basal and intermediate cells (Signoretti et al, Proc Natl Acad Sci U S A 2005). My current research aims at further defining stem cells and differentiation programs in the adult prostate and bladder epithelia. Specifically, we are performing genetic lineage tracing experiments to directly follow the fate of p63-positive cells in the prostate and bladder epithelia in vivo. The secondary goal of this endeavor is to identify molecular mechanisms mediating p63 function during both development and tumorogenesis. We have shown that prostate basal cells predominantly express the Np63 isosform and that Np63 is required for cell survival. Importantly, we have also demonstrated that Fatty Acid Synthase (FASN) is a functionally 6 relevant target of p63 and is required for mediating its pro-survival effects (Sabbisetti, PLoS ONE, 2009). Our results establish a novel functional link between this p53 family member and lipid metabolism and suggest that maintenance of fatty acid synthesis is a key mechanism through which p63 acts as a pro-survival molecule in both development and cancer. Research #2: Molecular Analysis Of Renal Cell Carcinoma Using Single Nucleotide Polymorphisms (SNP) Arrays Clear cell renal cell carcinoma (cRCC) represents the most common and fatal form of renal cancer and accounts for 70-80% of cases. In patients with advanced disease, response rates to traditional chemotherapy and radiotherapy are, unfortunately, very low. The introduction of cytokine-based immunotherapy with interferon- or interleukin-2 for patients with metastatic disease has shown survival improvements, but the treatment is often not well tolerated and only a limited subset of patients experience clinically meaningful benefit. Recently, tyrosine kinase inhibitors (TKIs) that target the VHL pathway, including sorafenib and sunitinib, have shown clear activity in metastatic cRCC and have received approval by the FDA. However, not all the patients treated with these targeted therapies experience a substantial clinical benefit and almost all of them eventually progress. Therefore, more effective treatments for cRCC are warranted. Kinases are tractable therapeutic targets with multiple small molecule inhibitors in development. Identification of new kinases that play an important role in the development and progression of cRCC would enable rapid development of more effective therapeutic approaches. Highthroughput genetic studies represent a unique opportunity to identify the tumor suppressor genes (TSGs) and oncogenes, including kinases, upon which genetic subtypes of cRCC depend. Highresolution single nucleotide polymorphism (SNP) arrays are able simultaneously to delineate regions of copy-number gain and loss and loss-of-heterozygosity (LOH) at high resolution throughout the genome. In collaboration with Drs. Kaelin and Beroukhim at DFCI and the Broad Institute, we are currently performing integrated analysis of SNP array data describing chromosomal aberrations with matched gene expression data to identify candidate kinases targeted by these aberrations in cRCC (Beroukhim et al, Cancer Res, 2009). Results from these studies will shed light on the molecular mechanisms underlying kidney cancer development and might eventually lead to more effective targeted therapies for this disease. D. Report of Teaching: 1. Local contributions Medical School Teaching 1995; 1998 1997 1998 Resident teaching: daily training of pathology Residents from University of Rome “la Sapienza”, rotating through the Pathology Service of Istituto Dermopatico dell’Immacolata. 4 Residents per year. Preparation and contact time: 1-3 hours/day. Resident teaching: Clinical Pathology rotation (of one month duration) in the Molecular Pathology Laboratory at Beth Israel Deaconess Medical Center. 6 Residents per year. Preparation and contact time: 510 hours/week. Istituto Dermopatico dell’Immacolata, Rome, Italy. Basic course in dermatopathology for Pathologists and Dermatologists. Lecturer. 10- 7 1999-2003 2001-2007 15 Post-doctoral Fellows. Duration of the course: 1 week. Preparation and contact time: 3 hours/day. Teaching and supervising of rotating Genetic Pathology Fellows from the Department of Pathology, Brigham and Women’s Hospital, Boston. 1 Post-doctoral Fellow per year. Duration of the rotation: 1 month. Preparation and contact time: 6-8 hours/week Pathology course, Harvard Medical School (course director: Dr. Andrew Lichtman), Tutor. 8-10 Medical Students. Preparation and contact time: 8-10 hours for each tutorial. Local Invited Teaching Presentations 2000 2002 2005 2005 2005 2006 2006 2007 2008 2009 2009 2009 2009 2010 2010 Dana-Farber Cancer Institute. Seminars in Genitourinary Oncology. Invited speaker: “p63 is a prostate basal cell marker and is required for prostate development”. Dana-Farber Cancer Institute. Seminars in Genitourinary Oncology. Invited speaker: “p63 and prostate stem cells”. Dana-Farber Cancer Institute. Seminars in Cancer Genomics. Invited Speaker: “Role of the F-box protein Skp2 in human breast cancer”. DF/HCC Kidney Cancer Program Meeting. Invited Speaker: “Molecular analysis of renal cell carcinoma using single nucleotide polymorphisms (SNP) arrays”. Brigham and Women’s Hospital. Thorn 5/6 Seminar Series. Invited Speaker: “p63 and Prostate Development”. DF/HCC Kidney Cancer Program Meeting. Invited Speaker: “Genome-wide analysis of genetic alterations in clear cell carcinoma of the kidney”. Beth Israel Deaconess Medical Center. GU Data Club. Invited Speaker. “p63 in genitourinary development”. DF/HCC Kidney Cancer Program Meeting. Invited Speaker: “Development of Clinically Relevant Mouse Orthotopic Xenografts of Human Renal Cell Carcinoma”. DF/HCC Kidney Cancer Program Meeting. Invited Speaker: “Mouse Orthotopic Xenografts of Human Renal Cell Carcinoma”. Harvard Urology and Prostate Cancer Research Seminar Series. Invited Speaker: “p63 and Prostate Cell Lineages”. Brigham and Women’s Hospital. Thorn 5/6 Seminar Series. Invited Speaker: “Non-Random Genetic Abnormalities in Kidney Cancer” Dana-Farber Cancer Institute. Seminars in Genitourinary Oncology. Invited speaker: “Defining cell lineages in the prostate epithelium”. Harvard Stem Cell Institute Retreat. Invited speaker: “Identification of stem cells in prostate and bladder epithelia”. Brigham and Women’s Hospital. Surgical Pathology Updates Seminar Series. Invited Speaker: “Molecular Pathology of Kidney Cancer”. Brigham and Women’s Hospital. Thorn 5/6 Seminar Series. Invited Speaker: “Molecular Characterization of Kidney Cancer” 8 2011 2011 DF/HCC Kidney Cancer Program Retreat. Invited Speaker: “Orthotopic Xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients”. Continuing Medical Education 2006 Harvard Medical School, Department of Continuing Education. Regional Renal Cancer Symposium: Recent Advances in the Biology and Treatment of Renal Cell Carcinoma. Invited Speaker: “Renal Cancer Pathology and Tissue Banking”. Advisory And Supervisory Responsibilities In Laboratory Setting 20032006; 2010 2007-2009 Supervising research activities of Post-doctoral Fellows and College Graduates. 30 hours/week Mentor. The DF/HCC Continuing Umbrella of Research Experiences (CURE) Program. 6 hours/week Mentor. Brigham and Women’s Hospital Student Success Jobs Program. 6 hours/week 2. Regional, National and International Contributions Regional presentations 1997 1998 1998 2007 University of Rome, Rome, Italy. Invited lecture: “Antigen receptor genes analysis in the diagnosis of cutaneous.lymphomas”. Istituto Dermopatico dell’Immacolata, Rome, Italy. Continuing medical education course: “Melanocytic nevi: histological features”. Istituto Dermopatico dell’Immacolata, Rome, Italy. Invited lecture: “Detection of clonal T-cell receptor gene rearrangements by PCRSSCP analysis”. University of Massachusetts Medical School, Genitourinary Program Seminars. Invited lecture: “p63 in genitourinary development”. National presentations 2002 2006 2006 2006 2006 Prouts Neck Prostate Cancer Meeting. Invited lecture: The basal cell marker p63 and prostate stem cells. 14th Annual SPORE Investigators’ Workshop, GU (Renal) Breakout Session. Invited lecture: “Predictive markers for response to CCI-779, IL-2, and sorafenib”. 2006 AUA/SBUR Summer Research Conference. Invited lecture: “p63 in bladder development”. Basic Research in Interstitial Cystitis: Second Investigators’ Meeting (NIH/NIDDK). Guest Speaker. “p63 in the development of the urothelium”. NCI-Sponsored Renal Cancer Biomarkers Workshop. Organizer and Invited Speaker. “Preparation and use of RCC Tissue Microarrays”. 9 2007 2008 15th Annual SPORE Investigators’ Workshop, GU (Renal) Breakout Session. Invited lecture: “Report on the NCI-Sponsored Renal Cancer Biomarkers Workshop”. Cambridge Conference on Innovations and Challenges in Renal Cancer. Invited lecture: “Tissue Biomarkers in Renal Cell Carcinoma: Issues and Solutions" International presentations 2000 2004 2006 2007 2008 2009 International Academy of Pathology, Alghero, Italy. Invited lecture: “The use of laser capture microdissection (LCM) in molecular pathology”. 5th World Congress on Urological Research, London, UK. Invited lecture: “Defining progenitor cells in the prostate epithelium”. The Kidney Cancer Association’s Fifth International Kidney Cancer Symposium. Invited lecture: “Predictive markers of response to therapy for advanced renal cancer”. CAIX Symposium- Brussels, Belgium. Invited lecture: “CAIX Expression as a Biomarker in Renal Cancer”. 2008 Prostate Cancer Research Foundation Forum, Toronto, Canada. Invited lecture: “Lineage commitment in prostate development”. 2009 ASCO Annual Meeting, Orlando, FL. Invited lecture: “Tumor biology to predict response and resistance in renal carcinoma”. E. Report of clinical activities: 1. Field: Dermatopathology. Teaching hospital: Staff pathologist, Istituto Dermopatico dell’Immacolata (1993-1995; 1998). 2. Patient load: 30,000 surgical pathology cases/year (1993-1995; 1998). 500 molecular diagnostic cases/year (1996-1997). 3. Clinical contributions: 1998 2000 Development of a PCR-based methodology for TCR gene rearrangement analysis in paraffin-embedded tissue, extensively used in routine clinical practice. Identification of p63 as a reliable marker of prostate basal cells that is not expressed in prostate carcinoma. p63 immunohistochemistry is currently used in routine clinical practice for the diagnosis of challenging prostate biopsies. 10 Part III Bibliography Original Articles 1. Di Tondo U, Ciardi A, Pecorella I, Signoretti S, Taccogna S, Berloco P, Cinti P, Caricato M, Iappelli M Alfani D, Cortesini R. Postoperative liver transplant monitoring with fine-needle aspiration biopsy. Transplant Proc. 1989;21:2311-12. 2. Muhlhauser J, Jones M, Yamada I, Cirielli C, Lemarchand P, Gloe TR, Bewig B, Signoretti S, Crystal RG, Capogrossi MC: Safety and efficacy of in vivo gene transfer into the porcine heart with replication-deficient, recombinant adenovirus vectors. Gene Ther. 1996;3:145-53. 3. Benucci R, Annessi G, Signoretti S, Simoni R: Minimally differentiated acute myeloid leukaemia revealed by specific cutaneous lesions. Brit J Dermatol. 1996;135:119-23. 4. Signoretti S, Annessi G, Occhiuto S, Ruatti P, Faraggiana T: Papular clear cell hyperplasia of the eccrine duct in a diabetic. Brit J Dermatol. 1996;135:139-43. 5. Annessi G, Signoretti S, Angelo C, Paradisi M, Puddu P: Neutrophilic figurate erythema of infancy. Am J Dermatopathol. 1997;19:403-06. 6. Cerroni L, Signoretti S, Hofler G, Annessi G, Putz B, Lackinger E, Metze D, Giannetti A, Kerl H: Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma. Am J Surg Pathol. 1997;21:1307-15. 7. Singh SP, Lipman J, Goldman H, Ellis FH Jr, Aizenman L, Cangi MG, Signoretti S, Chiaur DS, Pagano M, Loda M.: Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma. Cancer Res. 1998;58:1730-35. 8. Ascoli V, Nardi F, Carnovale Scalzo C, Signoretti S, Pistilli A, Lo Coco F. Absence of HHV-8 sequences in malignant mesotelioma. Mol Pathol, 1998;51:113-14. 9. Signoretti S, Annessi G. Are histopathological attributes of nevi and melanomas on volar skin related to skin markings? Dermatopathology: practical and conceptual. 1998;4:311-313. 10. Signoretti S, Annessi G, Puddu P, Faraggiana T: Melanocytic Nevi of palms and soles: a histological study according to the plane of section. Am J Surg Pathol. 1999;23:283-7. 11. Signoretti S, Murphy M, Cangi MG, Puddu P, Kadin ME, M. Loda. Detection of clonal Tcell receptor gene rearrangements by PCR and non-radioactive single strand conformational polymorphism (SSCP) analysis. Am J Pathol. 1999;154:67-75. 12. Murphy M, Signoretti S, Nasser I, Sherburne B, Loda M. Detection of concurrent/recurrent non-Hodgkin lymphomas in effusions by PCR. Hum Pathol. 1999;30:1361-6. 13. Signoretti S, Murphy M, Puddu P, DeCoteau JF, Faraggiana T, Kadin ME, Loda M. Improved detection of B-cell clonality by microdissection and PCR-IgH gene rearrangement analysis in the diagnosis of cutaneous B-cell infiltrates. Diag Mol Pathol. 1999;4:176-82. 14. Murphy M, Signoretti S, Kadin ME, Loda M. Detection of TCR- gene rearrangements in early mycosis fungoides by non-radioactive PCR-SSCP. J Cut Pathol. 2000;27:228-34. 11 15. Narducci MG, Pescarmona E, Lazzeri C, Signoretti S, Lavinia AM, Remotti D, Scala E, Baroni CD, Stoppacciaro A, Croce CM, Russo G. Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues. Cancer Res. 2000;60:2095-100. 16. Cangi MG, Cukor B, Soung P, Signoretti S, Moreira G, Ranashinge M, Cady B, Pagano M, Loda M. Role of the cdc25A phosphatase in human breast cancer. J Clin Invest. 2000;106: 753-61. 17. Gesbert F, Sellers WR, Signoretti S, Loda M, Griffin JD. Bcr/Abl regulates expression of the cyclin dependent kinase inhibitor p27 kip1through the PI3K/Akt pathway. J Biol Chem. 2000;275:39223-30. 18. Signoretti S, Montironi R Manola J, Altimari A, Tam C, Bubley G, Balk S, Thomas G, Kaplan I, Hlatky L, Hahnfeldt P, Kantoff P, Loda M. Her-2-neu expression and androgen independence in human prostate cancer. J Natl Cancer Inst. 2000;92:1918-25. 19. Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, McKeon F, Montironi R, Loda M. p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol. 2000;157:1769-75. 20. Nokamura N, Ramaswamy S, Vazquez, Signoretti S, Loda M, Sellers WR. Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN. Mol Cell Biol. 2000;20:8969-82. 21. Ascoli V, Signoretti S, Onetti Muda A, Della Rocca C, Mastroianni C M, Gastaldi R, Pescarmona E, Nardi F, Gaidiana G, Carbone A, Lo Coco F. Primary effusion lymphoma in HIV-infected patients with multicentric Castleman’s disease. J Pathol. 2001;193:200-9. 22. Datta MW, Macri’ E, Signoretti S, Renshaw A A, Loda M. Transition from in situ to invasive testicular germ cell neoplasia is characterized by the loss of p21 and gain of mdm-2 expression. Mod Pathol. 2001;14:437-42. 23. Waltregny D, Leav I, Signoretti S, Soung P, Lin D, Merk F, Adam YA, Bhattacharya N, Cirenei N, Loda M. Androgen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27 kip1 through its proteasome-mediated degradation. Mol Endocrinol. 2001;15:765-82. 24. Di Rienzo J, Signoretti S, Nakamura N, Rivera-Gonzales R, Sellers WR, Loda M, Brown M. Growth factor requirement and basal phenotype of immortalized mammary epithelial cells. Cancer Res. 2002 Jan 1;62(1):89-98. 25. Bardeesy N, Morgan J, Sinha M, Signoretti S, Srivastava S, Loda M, Merlino G, DePinho RA. Obligate role for p16Ink4a and p19arf-p53 in murine pancreatic neoplasia. Mol Cell Biol. 2002;22:635-43. 26. Lindeman N, Waltregny D, Signoretti S, Loda M. Gene transcript quantitation by real time RT-PCR in cells selected by immunohistochemistry-laser capture microdissection. Diag Mol Pathol. 2002;4:187-92. 27. Gounari F, Signoretti S, Klein L, Bronson R, Sellers WR, Kum J, Siermann A, Taketo MM, von Boehmer H, Khazaie K. Stabilization of -Catenin induces prostatic intraepithalial 12 neoplasia, but terminal squamous transdifferetiation of other secretory epithelia. Oncogene. 2002;21:4099-107. 28. Signoretti S, di Marcotullio L, Richardson A, Ramaswamy S, Carrano A C, Isaac B, Rue M, Monti F, Loda M and Pagano M. Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. J Clin Invest. 2002;110:633-41. 29. Bardeesy N, Sinha M, Hezel A F, Signoretti S, Hathaway N A, Sharpless N E, Loda M, Carrasco D R and DePinho RA. Loss of the Lkb1 tumor suppressor provokes intestinal polyposis but resistance to transformation. Nature. 2002;419:162-7. 30. Weinstein MH, Signoretti S, Loda M. Diagnostic utility of immunohistochemical staining for p63, a sensitive marker of prostatic basal cells. Mod Pathol. 2002;12:1302-1308. 31. Garraway LA, Lin D, Signoretti S, Waltregny D, Dilks J, Bhattacharya N, Loda M. Intermediate Basal Cells of the Prostate: In Vitro and In Vivo Characterization. Prostate. 2003;15:206-18. 32. Graner E, Tang D, Rossi S, Baron A, Migita T, Weinstein LJ, Lechpammer M, Huesken D, Zimmermeann J, Signoretti S, Loda M. The isopeptidase USP2a regulates the stability of Fatty Acid Synthase in prostate cancer. Cancer Cell. 2004; 5:253-61. 33. Murphy M, Carlson JA, Keough MP, Claffey KP, Signoretti S, Loda M. Hypoxia regulation of the cell cycle in malignant melanoma: putative role for the cyclin dependent kinase inhibitor p27. J Cutan Pathol. 2004;31:477-82. 34. Berger R, Febbo PG, Majumder PK , Zhao J, Mukherjee S, Signoretti S, Campbell KT, Sellers WR, Roberts TM, Loda M, Golub TR, Hahn WC. Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells. Cancer Res. 2004; 64:8867-75. 35. Horkan C, Dalal K, Coderre JA, Kiger JL, Dupuy DE, Signoretti S, Goldberg SN. Tumor ablation: reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model. Radiology. 2005;235(1):81-8. 36. Atkins MB, Regan M, McDermott D, Mier J, Stanbridge E, Youmans A, Febbo P, Upton M, Lechpammer M, Signoretti S. Carbonic Anhydrase IX Expression Predicts Outcome of IL-2 Therapy. Clin Cancer Res. 2005; 11:3714-21. 37. Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Zabaleta J, Quiceno D, Signoretti S, McDermott D, Youmans A, O’Neill A, Regan M, Mier J, Ochoa AC. Suppressor Myeloid Cells in Renal Cell Carcinoma Block T Cell Function and z Chain Expression. Cancer Res. 2005; 65:3044-8. 38. Ahmed M, Liu Z, Lukyanov AN, Signoretti S, Horkan C, Monsky WL, Torchilin VP, Goldberg SN. Combination radiofrequency ablation with intratumoral liposomal doxorubicin: effect on drug accumulation and coagulation in multiple tissues and tumor types in animals. Radiology. 2005; 235:469-77. 39. Luo J, Sobkiw CL, Logsdon NM, Watt JM, Signoretti S, O'connell F, Shin E, Shim Y, Pao L, Neel BG, Depinho RA, Loda M, Cantley LC. Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3kinase. Proc Natl Acad Sci (U S A). 2005; 102:10238-43. 13 40. Signoretti S*, Pires MM, Lindauer M, Horner JW, Grisanzio C, Dhar S, Majumder P, McKeon F, Kantoff PW, Sellers WR, Loda M*. p63 regulates commitment to the epithelial cell lineage. Proc Natl Acad Sci (U S A). 2005; 102:11355-60. 41. De Marzo AM, Platz EA, Epstein JI, Ali T, Billis A, Chan TY, Cheng L, Datta M, Egevad L, Ertoy-Baydar D, Farre X, Fine SW, Iczkowski K A, Ittmann M, Knudsen S, Loda M, LopezBeltran A, Magi-Galluzzi C, Mikuz G, Montironi R, Pikarsky E, Pizov G, Rubin M A, Samaratunga H, Sebo T, Sesterhenn IA, Shah RB, Signoretti S, Simko J, Thomas G, Troncoso P, Tsuzuki TT, van Leenders GJ, Yang XJ, Zhou M, Figg WD, Hoque A and Lucia MS. A working group classification of focal prostate atrophy lesions. Am J Surg Pathol. 2006; 30(10):1281-91. 42. Berger R, Lin DI, Nieto, Sicinska Ewa, L. Garraway LA, Heiner A, Signoretti S, Hahn WC and Loda M. Androgen-dependent regulation of Her-2/neu In Prostate Cancer Cells. Cancer Res. 2006; 66:5723-8. 43. Hines-Peralta A, Sukhatme V, Regan M, Signoretti S, Liu ZJ, Goldberg SN. Improved Tumor Destruction with Arsenic Trioxide and Radiofrequency Ablation in Three Animal Models. Radiology. 2006; 240(1):82-9. 44. Hakime A, Hines-Peralta A, Peddi H,. Atkins MB, Sukhatme VP, Signoretti S, Regan M, and Goldberg SN. Combination of radiofrequency with antiagiogenic therapy increases tumor ablation efficacy. Radiology. 2007; 244(2):464-70. 45. Zhan Q, Signoretti S, Whitaker-Menezes D, Friedman TM, Korngold R and Murphy GF. Cytokeratin15-Positive Basal Epithelial Cells Targeted in Graft-Versus-Host Disease Express a Constitutive Antiapoptotic Phenotype. J Invest Dermatol. 2006; 27(1):106-15. 46. Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, Macconnaill LE, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L, Majmudar K, Ziaugra L, Wong KK, Gabriel S, Beroukhim R, Peyton M, Barretina J, Dutt A, Emery C, Greulich H, Shah K, Sasaki H, Gazdar A, Minna J, Armstrong SA, Mellinghoff IK, Hodi FS, Dranoff G, Mischel PS, Cloughesy TF, Nelson SF, Liau LM, Mertz K, Rubin MA, Moch H, Loda M, Catalona W, Fletcher J, Signoretti S, Kaye F, Anderson KC, Demetri GD, Dummer R,Wagner S, Herlyn M, Sellers WR, Meyerson M, Garraway LA. High-throughput oncogene mutation profiling in human cancer. Nat Genet. 2007; 39(3):347-51. 47. Cho D, Signoretti S, Dabora S, Regan M, Seeley A, Mariotti M, Youmans A, Polivy A, Mandato L, McDermott D, Stanbridge E, Atkins M. Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma. Clin Genitourin Cancer. 2007;5(6):379-85. 48. Sabir A, Schor-Bardach R, Wilcox CJ, Rahmanuddin S, Atkins MB, Kruskal JB, Signoretti S, Raptopoulos VD, Goldberg SN. Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy. AJR Am J Roentgenol. 2008 Jul;191(1):133-9. 49. Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, Signoretti S, Kaelin WG Jr. Acute Loss of pVHL Actuates a HIF-independent Senescence Program Mediated by pRb and p400. Nat Cell Biol. 2008; 10(3):361-9. 14 50. Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, Zhang J, Signoretti S, Loda M, Roberts TM, and Zhao JJ. Kinase-dependent and -independent roles of PI3K-p110β in cell growth, metabolism and tumorigenesis. Nature. 2008;454(7205):776-9. 51. Majumder P, Grisanzio C, O’Connell F, Xu Q, Berger R, Herman P, Bikoff R, Baek WK, Wang S, Ellwood-Yen K, Hahn WC, Wu H, Sawyers CL, Signoretti S, Loda M, Sellers WR. A prostatic intraepithelial neoplasia-dependent p27kip1 checkpoint induces senescence, inhibits cell proliferation and cancer progression. Cancer Cell. 2008;14(2):146-55. 52. Hulick P, Zimmer M, Margulis V, Skates S, Hamel M, Dahl M. D, Michaelson D, Liebermann T, Signoretti S, Carney W, Wood C, Iliopoulos O. Blood Levels of Carbonic Anhydrase 9 Correlate with Clear Cell Renal Cell Carcinoma Activity. Clin Proteom. 2009; 5:37-45. 53. Xie H, Valera VA, Merino MJ, Amato AM, Signoretti S, Linehan WM, Sukhatme VP, Seth P. LDH-A Inhibition, a therapeutic strategy for treatment of Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). Mol Cancer Ther. 2009;8(3):626-35. 54. Migita T, Ruiz S, Fornari A, Inazuka F, Fiorentino M, Zadra G, Grisanzio C, Palescandolo E, Priolo C, Shin E, Fiore C, Xie W, Kung A, Febbo P, Subramanian A, Mucci L, Ma J, Signoretti S, Stampfer M, Hahn W, Finn S, Loda M. Fatty Acid Synthase: A Metabolic Enzyme and Candidate Oncogene in Prostate Cancer. J Natl Cancer Inst. 2009;101(7):51932. 55. Walker SR, Nelson EA, Zou L, Chaudhury M, Signoretti S, Richardson A, Frank DA. Reciprocal effects of STAT5 and STAT3 in breast cancer. Mol Cancer Res. 2009 Jun 2. [Epub ahead of print]. 56. Wiklund F, Tretli S, Choueiri TK, Signoretti S, Fall K, Adami HO. The risk of bilateral renal cell cancer. J Clin Oncol. 2009;27:3737-41. 57. Schor-Bardach R, Alsop DC, Pedrosa I, Solazzo SA, Wang X, Marquis RP, Atkins MB, Regan M, Signoretti S, Lenkinski RE, Goldberg SN. Does Arterial Spin-labeling MR Imaging–Measured Tumor Perfusion Correlate with Renal Cell Cancer Response to Antiangiogenic Therapy in a Mouse Model? Radiology. 2009;251(3):731-42. 58. Beroukhim R, Brunet JP, Di Napoli A, Mertz KD, Seeley A, Pires MM, Linhart D, Worrell RA, Moch H, Rubin, RA, Sellers WR, Meyerson M, W Linehan M, Rubin M, Kaelin WG, Signoretti S. Patterns of gene expression and copy-number alterations in VHL diseaseassociated and sporadic clear cell carcinoma of the kidney. Cancer Res. 2009;69(11):467481. 59. Sabbisetti S, Di Napoli A, Seeley A, Amato AM, O’Regan E, Ghebremichael M, Loda M, Signoretti S. p63 Promotes Cell Survival Through Fatty Acid Synthase. PLoS ONE. 2009;4(6):e5877. 60. Solazzo SA, Ahmed M, Schor-Bardach R, Yang W, Girnun GD, Rahmanuddin S, Levchenko T, Signoretti S, Spitz DR, Torchilin V, Goldberg SN. Liposomal Doxorubicin Increases Radiofrequency Ablation-induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways. Radiology. 2010 255(1):62-74. 15 61. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, McHenry K, Pinchback R, Ligon AH, Cho J, Haery L, Greulich H, Reich M, Winckler W, Weir BA, Tanaka K, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Baselga J, Tsao M, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Lander ES, Getz G, Golub TR, Sellers WR, Meyerson M. The landscape of copy number alterations across multiple human cancers. Nature. 2010;463:899-905. 62. Choueiri TK, Regan MM, Rosenberg JE, Oh WK, Clement J, Amato AM, McDermott D, Cho DC, Atkins MB, Signoretti S. Carbonic anhydrase IX (CAIX) and pathologic features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving VEGF-targeted therapy. BJU Int. 2010;106(6):772-8. 63. Lee SH, Poulogiannis G, Pyne S, Jia S, Zou L, Signoretti S, Loda M, Cantley LC, and Roberts TM. A constitutively activated form of the p110β isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice. Proc Natl Acad Sci (U S A). 2010;107(24):110027. 64. Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, Signoretti S, Mier JW. The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 Compared to Rapamycin in Renal Cell Carcinoma. Clin Cancer Res. 2010;16(14):3628-38. 65. Yang W, Ahmed M, Elian M, Hady ES, Levchenko TS, Sawant RR, Signoretti S, Collins M, Torchilin VP, Goldberg SN. Do Liposomal Apoptotic Enhancers IncreaseTumor Coagulation and End-Point Survival in Percutaneous Radiofrequency Ablation of Tumors in a Rat Tumor Model? Radiology 2010 Sep 21. [Epub ahead of print]. 66. Genega, EM, Ghebremichael, M, Najarian R, Fu Y, Wang, Y, Argani, P, Grisanzio, C, Signoretti S. CAIX Expression in Renal Neoplasms: Correlation with Tumor Type and Grade. Am J Clin Pathol. 2010;134(6):873-9. 67. Bhatt R, Wang X, Zhang L, Collins M, Signoretti S, Alsop D, Goldberg SN, Atkins MB, Mier JW. Renal cancer resistance to antiangiogenic therapy is delayed by restoration of angiostatic signaling. Mol Cancer Ther. 2010:9(10):2793-802. 68. Moslehi J, Minamishima YA, Padera RF, Signoretti S, Liao R, and Kaelin WG. Loss of PHD Prolyl Hydroxylase Activity in Cardiomyocytes Phenocopies Ischemic Cardiomyopathy. Circulation. 2010;122(10):1004-16. 69. Gan B, Lim C, Chu G, Hua S, Ding Z,Collins M, Hu J, Jiang S, Fletcher-Sananikone E, Zhuang L, Chang M, Zheng H, Wang YA, Kwiatkowski DJ, Kaelin WG, Signoretti S and DePinho RA. FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. Cancer Cell. 2010;18(5):472-84. 70. Ding Z, Wu C, Chu GC, Xiao Y, Ho D, Zhang J, Perry SR, Labrot ES, Wu X, Lis R, Hoshida Y, Hiller D, Hu B, Jiang S, Zheng H, Stegh AH, Scott AL, Signoretti S, El-Bardeesy NM, Wang YA, Hill D, Golub TR, Stampfer MJ, Wong WH, Loda M, Mucci L, Chin L & 16 DePinho RA. SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Nature. 2011;470(7333):269-73. 71. Bernardi R, Papa A, Egia A, Coltella N, Teruya-Feldstein J, Signoretti S and Pandolfi PP. Pml represses tumor progression through inhibition of mTOR. EMBO Mol Med. 2011;3(5):249-57. 72. Flavin R, Finn SP, Choueiri TK, Ingoldsby H, Ring M, Barrett C, Rogers M, Smyth P, O'Regan E, Gaffney E, O'Leary JJ, Loda M, Signoretti S, Sheils O. RET protein expression in papillary renal cell carcinoma. Urol Oncol. 2011 Mar 9. [Epub ahead of print]. 73. Lee SH, Jia S, Zhu Y, Utermark T, Signoretti S, Loda M, Schaffhausen B, Roberts TM. Transgenic expression of polyoma virus middle T antigen in the mouse prostate gives rise to carcinoma. J Virol. 2011;85(11):5581-92. 74. Zhang L, Bhasin M, Schor-Bardach; R, Wang X, Collins MP, Panka D, Putheti P, Signoretti S, Alsop DC, Libermann T, Atkins MB, Mier JW, Goldberg NS, Bhatt RS. Resistance of renal cell carcinoma to sorafenib is mediated by potentially reversible gene expression. PLoS ONE. 2011;6(4):e19144. 75. Grisanzio C, Seeley A, Chang M, Collins M, Di Napoli A, Cheng SC, Percy A, Beroukhim R, Signoretti S. Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients. J Pathol. 2011 May 2. [Epub ahead of print]. 76. Shen C, Beroukhim R, Schumacher S, Zhou J, Chang M, Signoretti S, and Kaelin WG. Genetic and Functional Studies Implicate HIF1alpha as a 14q Kidney Cancer Suppressor Gene. Cancer Discovery. 2011;1:222-235 77. Lin W, Cao J, Liu J, Beshiri ML, Fujiwara Y, Francis J, Cherniack AD, Geisen C, Blair LP, Zou MR, Shen X, Kawamori D, Liu Z, Grisanzio C, Watanabe H, Minamishima YA, Zhang Q, Kulkarni RN, Signoretti S, Rodig SJ, Bronson RT, Orkin SH, Tuck DP, Benevolenskaya EV, Meyerson M, Kaelin WG, and Yan Q. Loss of the RBP2 histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci (U S A). 2011;108:1337986. 78. Yang W, Ahmed M, Tasawwar B, Levchenko T, Sawant RR, Collins M, Signoretti S, Torchilin V, Goldberg SN. Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model. Int J Hyperthermia. 2011;27(6):527-38. 79. Bass AJ, Lawrence MS, Brace LE, Ramos AH, Drier Y, Cibulskis K, Sougnez C, Voet D, Saksena G, Sivachenko A, Jing R, Parkin M, Pugh T, Verhaak RG, Stransky N, Boutin AT, Barretina J, Solit DB, Vakiani E, Shao W, Mishina Y, Warmuth M, Jimenez J, Chiang DY, Signoretti S, Kaelin WG, Spardy N, Hahn WC, Hoshida Y, Ogino S, Depinho RA, Chin L, Garraway LA, Fuchs CS, Baselga J, Tabernero J, Gabriel S, Lander ES, Getz G, Meyerson M. Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1ATCF7L2 fusion. Nat Genet. 2011 Sep 4 [Epub ahead of print]. * Co-corresponding authors. 17 Review Articles and Editorials 1. Signoretti S, Loda M. Estrogen receptor beta in prostate cancer: brake pedal or accelerator? Am J Pathol 2001;159:13-6. 2. Signoretti S and Loda M. Defining stem cells in the prostate epithelium. Cell Cycle. 2006; 5:138-41. 3. Cho D, Signoretti S, Regan M, Mier JW, Atkins MB. The role of mammalian target of rapamycin inhibitors in the treatment of advanced renal cancer. Clin Cancer Res. 2007;13(2 Pt 2):758s-763s. 4. Signoretti S and Loda M. Prostate stem cells: from development to cancer. Semin Cancer Biol. 2007; 17(3):219-24. 5. Grisanzio C and Signoretti S. p63 in prostate biology and pathology. J Cell Biochem. 2008; 103(5):1354-68. 6. Signoretti S, Regan M, Atkins MB. Carbonic Anhydrase IX (CAIX) as a predictive biomarker of response to kidney cancer therapy. BJU Int. 2008; 101 Suppl 4:31-5. 7. Signoretti S, Bratslavsky G, Waldman FM, Reuter VE, Haaga J, Merino M, Thomas GV, Pins MR, Libermann T, Gillespie J, Tomaszewski JE, Compton CC, Hruszkewycz A, Linehan WM, Atkins MB. Tissue-Based Research In Kidney Cancer: Current Challenges And Future Directions. Clin Cancer Res. 2008;14(12):3699-705. 8. Signoretti S. Tissue-Based Research in the Era of ‘Personalized Medicine’: Biomarkers, Microarrays, and Beyond. Kidney Cancer Journal. 2008;235-9. 9. Di Napoli A and Signoretti S. Tissue Biomarkers in Renal Cell Carcinoma: Issues and Solutions. Cancer. 2009;115(10 Suppl):2290-7. 10. Atkins MB, Choueiri TK, Cho D, Regan M, Signoretti S. Treatment Selection for Patients With Metastatic Renal Cell Carcinoma. Cancer. 2009;115(10 Suppl):2327-33. 11. Atkins MB, Bukowski RM, Escudier BJ, Figlin RA, Hudes GH, Kaelin WG Jr, Linehan WM, McDermott DF, Mier JW, Pedrosa I, Rini BI, Signoretti S, Sosman JA, The BT, Wood CG, Zurita, AJ and King L. Innovations and Challenges in Renal Cancer: Summary Statement From the Third Cambridge Conference. Cancer. 2009;115(10 Suppl):2247-51. Chapters in Books 1. Kamino H, Signoretti S, Weedon D. Site specific nevi. In “WHO classification of tumors: Pathology and Genetics of Skin Tumors”. Edited by LeBoit PE, Burg G, Weedon D, Sarasin A. 2. Grisanzio C and Signoretti S. Adult Prostate Epithelium Renewal, Stem Cells and Cancer. In “Stem Cells and Cancer”. Edited by Rebecca G. Bagley and Beverly A. Teicher. 2009. 3. Bahamon B and Signoretti S. Tissue Biomarkers in Renal Cell Carcinoma: Intermediate Endpoints in the Selection of Targeted Agents for RCC. In “Renal Cell Carcinoma: 18 Biology, Prognostic Factors and Therapeutic Targets”. Edited by Kimryn Rathmell, Brian Rini and Robert A. Figlin. In Press. Thesis 1. M.D. Thesis: Signoretti S. Cyclosporin nephrotoxicity in kidney transplantation. University of Rome, 1988. 2. Pathology Residency Thesis: Signoretti S. Congenital cystic adenomatoid, malformation of the lung. University of Rome, 1993. Patents 1. 1999. Loda M, Macri’ E, Signoretti S. “Cdx-2 as a unique marker of colon carcinoma” 2. 1999. Harvard Medical School, Harvard Case #1674. McKeon F, Yang A, Loda M, Signoretti S, Crum C. “p63 expression pattern in the classification of malignancies of the prostate, cervix and breast” Abstracts (Unpublished work) 1. Grisanzio C, Sabbisetti V, Browne D, Signoretti S. p63 in Development and Maintenance of the Prostate Epithelium. Department of Defense Prostate Cancer Research Program Meeting. Innovative minds in Prostate Cancer Today (IMPaCT). Atlanta, Georgia 2007. 2. Han WK, Hsiao L, Signoretti S, Bonventre JV, Steele G. Kidney Injury Molecule- (KIM-1) and carbonic Anhydrase IX (CAIX) as Urinary Biomarkers for Renal Cell Carcinoma. J Am Soc Nephrol. 2007; 18:222A. 3. Di Napoli A, Grisanzio C, Ghebremichael M, Seeley A, Amato AM, Atkins MB, Signoretti S. CAIX Expression Correlates with VHL Mutational Status in Sporadic Clear Cell Carcinoma of the Kidney. Annual Meeting United States and Canadian Division of the International Academy of Pathology, Denver, Colorado, 2008. 19