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CURRICULUM VITAE Part I General Information DATE PREPARED ...
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<strong>CURRICULUM</strong> <strong>VITAE</strong><br />
<strong>Part</strong> I <strong>General</strong> <strong>Information</strong><br />
<strong>DATE</strong> <strong>PREPARED</strong> 09/09/11<br />
Name: Sabina Signoretti, M.D.<br />
Office Address: Department of Pathology,<br />
Brigham and Women’s Hospital, Thorn 504A<br />
75 Francis Street<br />
Boston MA 02115<br />
Ph : 617-525-7437<br />
e-mail: ssignoretti@partners.org<br />
Home Address: 77 Wenham Street Apt.2, Jamaica Plain, MA 02130<br />
Work E:Mail: ssignoretti@partners.org Work FAX: 617-264-5169<br />
Place of birth:<br />
Education:<br />
Rome, Italy<br />
1982-1988 M.D. University of Rome “La Sapienza”, Rome, Italy<br />
Postdoctoral Training:<br />
Residencies:<br />
1989-1993<br />
Fellowships:<br />
Resident in Pathology, University of Rome “La Sapienza”<br />
1995-1996 Research Fellow in Hematopathology, Beth Israel Hospital, Boston,<br />
MA<br />
1996-1997 Research Fellow in Molecular Pathology, Beth Israel Deaconess<br />
Medical Center, Boston MA.<br />
Licensure and Certification:<br />
1988 State licensure examination, Italy<br />
Academic Appointments:<br />
1996-1997 Research Fellow, Harvard Medical School, Boston, MA<br />
1999-2003 Instructor in Pathology, Harvard Medical School<br />
2003-2008 Assistant Professor of Pathology, Harvard Medical School<br />
2009- Associate Professor of Pathology, Harvard Medical School<br />
Hospital Appointments:<br />
1993-1995; 1998 Attending Pathologist, Istituto Dermopatico dell'Immacolata (IDI),<br />
Rome, Italy<br />
1999-2003 Research Associate, Brigham and Women’s Hospital<br />
1999- Associate Pathologist, Dana-Farber Cancer Institute<br />
2003- Associate Pathologist, Brigham and Women’s Hospital<br />
1
2006- Affiliate Faculty, Harvard Stem Cell Institute<br />
2006- Member, DFCI/BWH Center for Molecular Oncologic Pathology<br />
2011- Visiting Postdoctoral Scholar, Broad Institute of Harvard and MIT<br />
Hospital and Health Care Organization Responsabilities:<br />
1993-1995; 1998 Diagnostic Dermatopathology, Istituto Dermopatico<br />
dell'Immacolata (IDI), Rome, Italy<br />
1996-1997 Supervisor of the Core Molecular Pathology Laboratory at<br />
Beth Israel Deaconess Medical Center<br />
1999-2004 Associate Pathologist, Prostate Cancer Pathology Core Facility and In<br />
situ Hybridization Core Facility, Dana-Farber Harvard Cancer Center<br />
(DF/HCC)<br />
2005- Associate Pathologist, Specialized Histopathology Core Facility,<br />
Dana-Farber Harvard Cancer Center (DF/HCC)<br />
Major Administrative Responsibilities:<br />
Local<br />
2004- Director, Tissue Acquisition Pathology and Clinical Data Core of<br />
DF/HCC Kidney Cancer SPORE and Program<br />
2008- Director, DF/HCC Tissue Microarray and Imaging (TMI) Core<br />
2010- Co-Leader, DF/HCC Kidney Cancer Program<br />
Major Committee Assignments:<br />
Local<br />
2004- Member, DF/HCC Kidney Cancer SPORE Governance Committee<br />
2004- Co-chair, DF/HCC Kidney Cancer SPORE Specimens & Data<br />
Utilization Committee<br />
2005- Member, DF/HCC Specialized Histopathology Core Facility User<br />
Committee<br />
2005- Member, DF/HCC Tissue Microarray Core Facility User Committee<br />
2008- Member, DFCI/BWH Center for Molecular Oncologic Pathology<br />
Advisory Committee<br />
2008- Member, DF/HCC Scientific Council<br />
2009- Member, Urologic Disease Working Group of The Cancer Genome<br />
Atlas (TCGA) Program (NCI/ NHGRI)<br />
2010- Member, NCI Renal Cancer Task Force (RCTF)<br />
2011- Kidney Cancer Analysis Working Group of The Cancer Genome Atlas<br />
(TCGA) Program (NCI/ NHGRI)<br />
Professional Societies (Member):<br />
1999- American association for Cancer Research<br />
New England Society of Pathologists<br />
US and Canadian Academy of Pathology<br />
Grant review activities:<br />
2
2003 Scientific Reviewer, Cell Biology Review Panel #1, Department of<br />
Defense Prostate Cancer Research Program<br />
2004- 2005 Scientific Reviewer, Pathobiology Review Panel #3, Department of<br />
Defense Prostate Cancer Research Program<br />
2006- Scientific Reviewer, Pathobiology Review Panel #2, Department of<br />
Defense Prostate Cancer Research Program<br />
Community Service Related to Professional Work:<br />
2006; 2010 Mentor, DF/HCC Continuing Umbrella of Research Experiences<br />
(CURE) Program<br />
2007- 2009<br />
Editorial activities:<br />
Mentor, <strong>Part</strong>ners Student Success Jobs Program, Brigham and<br />
Women’s Hospital<br />
2004- Ad hoc reviewer:<br />
American Journal of Pathology, American Journal of Physiology,<br />
Breast Cancer Research, British Journal of Cancer, BJU International,<br />
Cancer, Cancer Research, Clinical Cancer Research, Development,<br />
Developmental Biology, Diagnostic Molecular Pathology, Human<br />
Pathology, International Journal of Cancer, Journal of Urology,<br />
Laboratory Investigation, Lancet Oncology, Nature Medicine, PLoS<br />
ONE<br />
2008-<br />
Awards and Honors:<br />
Member, Editorial Board:<br />
Clinical Cancer Research<br />
Diagnostic Molecular Pathology<br />
1988 M.D, summa cum laude, University of Rome<br />
1998 The Daland Award, The New England Cancer Society, Worcester, MA<br />
2001 Hershey Young Investigator Award, Boston MA<br />
2002 CaP CURE Award<br />
2007 <strong>Part</strong>ners in Excellence Award, Student Success Jobs Program Mentor<br />
<strong>Part</strong> II Research, Teaching, and Clinical Contribution<br />
A. Narrative Report:<br />
Research contributions: My research is focused on genitourinary malignancies, including<br />
prostate, bladder and renal cancer.<br />
Defining the cell(s) of origin of tumors is fundamental to elucidate the molecular mechanisms<br />
involved in their pathogenesis. A major limitation for the identification of the cell type(s)<br />
involved in the initiation and propagation of prostate and bladder cancers is that the identity of<br />
stem cells and differentiation programs in these epithelia remains unclear. My research aims to<br />
identify cell lineages in the prostate and bladder urothelium. I have previously demonstrated that<br />
p63 is selectively expressed in basal cells of the prostate and urothelium and that p63-deficient<br />
mice present defects in the development of these tissues. My subsequent studies have shown that<br />
the early developing prostate (prostate buds) consists exclusively of p63-positive basal cells,<br />
3
which then give rise to secretory cells and thus represent progenitor/stem cells. In contrast, my<br />
analysis of the urothelium shows that umbrella (superficial) cells can develop and be maintained<br />
independently from p63-positive cells. I am currently utilizing animal models to further<br />
characterize the role of p63 in the development and renewal of the prostate and bladder<br />
epithelium. This approach is likely to offer new insights in the biology of prostate and bladder<br />
development and open new perspectives in the identification of the cell of origin of prostate and<br />
bladder carcinoma.<br />
An important focus of my research in kidney cancer is the identification of novel oncogenes and<br />
tumor suppressor genes. In collaboration with Drs. Kaelin and Beroukhim at DFCI and the<br />
Broad Institute, we are currently using an integrated analysis of single-nucleotide polymorphism<br />
(SNP) arrays data with matched gene expression data to identify genes targeted by non-random<br />
genetic aberrations in RCC. Results from these studies have the potential to identify new drug<br />
targets and may eventually lead to new therapeutic approaches for patients with kidney cancer.<br />
My laboratory is also very involved in translational research activities. I currently serve as the<br />
Director of the Tissue Acquisition, Pathology, and Clinical Data (TAPCD) Core of the DF/HCC<br />
Kidney Cancer SPORE and Program. I am also the Director of the DF/HCC Tissue Microaaray<br />
and Imaging Core.<br />
Teaching contributions: I have been actively involved in teaching since the beginning of my<br />
career. I daily teach and tutor post-doctoral fellows and research assistant working in my<br />
research laboratory. Moreover, I serve as a Tutor in the Pathology course at Harvard Medical<br />
School.<br />
Clinical contributions: Throughout my career I have been involved in both patient care and in<br />
the development of new tools that could be helpful in the diagnosis and treatment of diseases.<br />
As a Research Fellow, I developed a novel PCR-based T-cell clonality assay, which is currently<br />
being utilized for the diagnosis of T-cell lymphomas (Signoretti et al., Am J Pathol, 1999 and<br />
accompanying editorial). More recently, I demonstrated that p63 is a reliable marker of prostate<br />
basal cells that is not expressed in prostate carcinoma. After extensive validation by other<br />
groups, p63 immunohistochemistry is currently used in routine clinical practice for the<br />
evaluation of challenging prostate biopsies.<br />
B. Funded Research Support:<br />
Past<br />
1996-1997 Oncor, Inc. Evaluation of the Oncor HER-2/neu (ERBB2) gene<br />
amplification detection kit for the interpahse detection of HER-2/neu<br />
(ERBB2) genomic sequences in human breast tissue for node-negative<br />
primary breast cancer. Multi-institutional study for FDA approval of<br />
the HER-2/neu (ERBB2) gene amplification detection kit. (Kit FDA<br />
approved Jan 1998). Co-investigator.<br />
1997-1998 Ministero della Pubblica Istruzione, Rome, Italy. Detection of B-cell<br />
clonality in cutaneous B-cell infiltrates. Co-investigator.<br />
2001 Hershey Foundation Award (Signoretti, DFCI). A mouse model for<br />
prostate stem cells. Principal Investigator.<br />
2001-2004 DOD U.S. Army, CDMRP - New Investigator Award (Signoretti,<br />
DFCI). The basal cell marker p63 and prostate stem cells. Principal<br />
Investigator.<br />
4
2002 CaP CURE Foundation Award (Signoretti, DFCI). An animal model<br />
for the identification of prostate stem cells. Principal Investigator.<br />
2002-2007 NIH/NCI. Prostate Cancer SPORE / Pathology Core (Kantoff, DFCI).<br />
Co-investigator.<br />
2004-2006 NIH/NCI. Kidney Cancer SPORE Developmental Project (Signoretti,<br />
BWH). Molecular analysis of renal cell carcinoma using Single<br />
Nucleotide Polymorphisms (SNP) arrays. Principal Investigator.<br />
2005-2007 NIH/NIDDK-R21. Defining cell lineages in the bladder urothelium<br />
(Signoretti, BWH). Principal Investigator.<br />
2006-2008 NIH/NCI. Kidney Cancer SPORE Developmental Project.<br />
Development of mouse orthotopic xenografts of human renal cell<br />
carcinoma (Signoretti, BWH). Principal Investigator.<br />
02/08/06-02/07/10 DOD. U.S. Army. CDMRP - Idea Development Award. p63 in<br />
development and maintenance of the prostate epithelium (Signoretti,<br />
BWH). Principal Investigator.<br />
2007 NIH/NCI. ICBP Pilot Project supported by 5U54 CA112962-03<br />
(Golub, DFCI). Integrating gene expression with high-resolution<br />
genetic analysis to identify oncogenic kinases in kidney cancer.<br />
Principal Investigator.<br />
01/01/07-12/31/08 Doris Duke Charitable Foundation. Distinguished Clinical Scientist<br />
Award (Kaelin, DFCI). Co-investigator.<br />
06/01/07-06/30/09 Harvard Stem Cell Institute. Seed Grant. Identification of Stem Cells<br />
In Prostate and Bladder Epithelia (Signoretti, BWH). Principal<br />
Investigator.<br />
09/01/09 – 08/31/10 NIH/NCI. of the Kidney Cancer SPORE P50 CA101942 -<br />
Developmental Project. Clinical, histological and molecular<br />
determinants of bilateral renal cell cancer. Principal Investigator.<br />
Current<br />
Active<br />
04/01/01-03/31/11 NIH/NCI. PO1 CA089021. The Role of PTEN and PI3K Pathway in<br />
Prostate Cancer (Cantley, BIDMC). Co-investigator.<br />
2005-2011 NIH/NCI. DF/HCC P30 CA06516. Specialized Histopathology Core<br />
(Aster, BWH). Co-investigator.<br />
2008-2011 NIH/NCI. DF/HCC P30 CA06516. Tissue Microarray and Imaging<br />
(TMI) Core (Signoretti, BWH). Principal Investigator.<br />
06/01/09-05/31/14 NIH/NCI. Kidney Cancer SPORE P50 CA101942. Tissue Acquisition<br />
Pathology and Clinical Data Core (CORE# 3) (Signoretti, BWH).<br />
Principal Investigator.<br />
06/01/09-05/31/14 NIH/NCI. Kidney Cancer SPORE P50 CA101942. Treatment of<br />
VHL-/- clear cell renal carcinoma with HIF2 siRNA (Kaelin DFCI,<br />
Choueiri DFCI, Signoretti BWH). Co-Principal Investigator of<br />
Project 2.<br />
5
09/01/10 – 07/31/15 NIH/NIDDK. 1R01DK089975 (Signoretti, BWH). Mechanisms<br />
Regulating Prostate Epithelium Maintenance and Regeneration.<br />
Principal Investigator.<br />
C. Current Research Activities<br />
#1: Role of p63 in development and renewal of the prostate and bladder epithelium<br />
Unraveling the mechanisms regulating the development and renewal of normal tissues is not<br />
only one of the main goals of developmental biology but also an essential step for the elucidation<br />
of the mechanisms underlying the development of pathological processes, namely cancer.<br />
Although epithelial stem cells have been identified in the skin and intestine, the way the prostate<br />
and bladder epithelium are formed and maintained remains unclear.<br />
The basal cell marker p63 is selectively expressed in the basal cells of several epithelia,<br />
including the prostate and the bladder. My research group has previously demonstrated that p63deficient<br />
(p63-/-) mice present defects in prostate buds and urothelial development (Signoretti et<br />
al., Am J Pathol 2000). We have more recently performed in vivo studies utilizing the p63-/mouse<br />
as a tool to define cell lineages in the prostate epithelium and urothelium. Results from<br />
these studies show that when developmental defects of p63-/- embryos are abolished by injecting<br />
p63+/+ ES cells into 3.5dpc p63-/- blastocysts, only p63+/+ cells compose the normal prostate<br />
epithelium of 7-weeks old chimeric mice. These findings indicate that prostate secretory cells of<br />
young adult mice derive from p63-positive progenitor cells that constitute the prostate buds.<br />
Surprisingly, in contrast with the prostate findings, analysis of the urothelium of the rescued p63-<br />
/- chimeras demonstrates that urothelial umbrella cells can develop independently from p63positive<br />
basal and intermediate cells (Signoretti et al, Proc Natl Acad Sci U S A 2005).<br />
My current research aims at further defining stem cells and differentiation programs in the adult<br />
prostate and bladder epithelia. Specifically, we are performing genetic lineage tracing<br />
experiments to directly follow the fate of p63-positive cells in the prostate and bladder epithelia<br />
in vivo.<br />
The secondary goal of this endeavor is to identify molecular mechanisms mediating p63 function<br />
during both development and tumorogenesis. We have shown that prostate basal cells<br />
predominantly express the Np63 isosform and that Np63 is required for cell survival.<br />
Importantly, we have also demonstrated that Fatty Acid Synthase (FASN) is a functionally<br />
relevant target of p63 and is required for mediating its pro-survival effects (Sabbisetti, PLoS<br />
ONE, 2009). Our results establish a novel functional link between this p53 family member and<br />
lipid metabolism and suggest that maintenance of fatty acid synthesis is a key mechanism<br />
through which p63 acts as a pro-survival molecule in both development and cancer.<br />
Research #2: Molecular Analysis Of Renal Cell Carcinoma Using Single Nucleotide<br />
Polymorphisms (SNP) Arrays<br />
Clear cell renal cell carcinoma (cRCC) represents the most common and fatal form of renal<br />
cancer and accounts for 70-80% of cases. In patients with advanced disease, response rates to<br />
traditional chemotherapy and radiotherapy are, unfortunately, very low. The introduction of<br />
cytokine-based immunotherapy with interferon- or interleukin-2 for patients with metastatic<br />
disease has shown survival improvements, but the treatment is often not well tolerated and only a<br />
limited subset of patients experience clinically meaningful benefit. Recently, tyrosine kinase<br />
inhibitors (TKIs) that target the VHL pathway, including sorafenib and sunitinib, have shown<br />
6
clear activity in metastatic cRCC and have received approval by the FDA. However, not all the<br />
patients treated with these targeted therapies experience a substantial clinical benefit and almost<br />
all of them eventually progress. Therefore, more effective treatments for cRCC are warranted.<br />
Kinases are tractable therapeutic targets with multiple small molecule inhibitors in development.<br />
Identification of new kinases that play an important role in the development and progression of<br />
cRCC would enable rapid development of more effective therapeutic approaches. Highthroughput<br />
genetic studies represent a unique opportunity to identify the tumor suppressor genes<br />
(TSGs) and oncogenes, including kinases, upon which genetic subtypes of cRCC depend. Highresolution<br />
single nucleotide polymorphism (SNP) arrays are able simultaneously to delineate<br />
regions of copy-number gain and loss and loss-of-heterozygosity (LOH) at high resolution<br />
throughout the genome. In collaboration with Drs. Kaelin and Beroukhim at DFCI and the Broad<br />
Institute, we are currently performing integrated analysis of SNP array data describing<br />
chromosomal aberrations with matched gene expression data to identify candidate kinases<br />
targeted by these aberrations in cRCC (Beroukhim et al, Cancer Res, 2009). Results from these<br />
studies will shed light on the molecular mechanisms underlying kidney cancer development and<br />
might eventually lead to more effective targeted therapies for this disease.<br />
D. Report of Teaching:<br />
1. Local contributions<br />
Medical School Teaching<br />
1995; 1998 Resident teaching: daily training of pathology Residents from<br />
University of Rome “la Sapienza”, rotating through the Pathology<br />
Service of Istituto Dermopatico dell’Immacolata. 4 Residents per year.<br />
Preparation and contact time: 1-3 hours/day.<br />
1997 Resident teaching: Clinical Pathology rotation (of one month duration)<br />
in the Molecular Pathology Laboratory at Beth Israel Deaconess<br />
Medical Center. 6 Residents per year. Preparation and contact time: 5-<br />
10 hours/week.<br />
1998 Istituto Dermopatico dell’Immacolata, Rome, Italy. Basic course in<br />
dermatopathology for Pathologists and Dermatologists. Lecturer. 10-<br />
15 Post-doctoral Fellows. Duration of the course: 1 week. Preparation<br />
and contact time: 3 hours/day.<br />
1999-2003 Teaching and supervising of rotating Genetic Pathology Fellows from<br />
the Department of Pathology, Brigham and Women’s Hospital,<br />
Boston. 1 Post-doctoral Fellow per year. Duration of the rotation: 1<br />
month. Preparation and contact time: 6-8 hours/week<br />
2001-2007 Pathology course, Harvard Medical School (course director: Dr.<br />
Andrew Lichtman), Tutor. 8-10 Medical Students. Preparation and<br />
contact time: 8-10 hours for each tutorial.<br />
Local Invited Teaching Presentations<br />
2000 Dana-Farber Cancer Institute. Seminars in Genitourinary Oncology.<br />
Invited speaker: “p63 is a prostate basal cell marker and is required for<br />
prostate development”.<br />
7
2002 Dana-Farber Cancer Institute. Seminars in Genitourinary<br />
Oncology. Invited speaker: “p63 and prostate stem cells”.<br />
2005 Dana-Farber Cancer Institute. Seminars in Cancer Genomics. Invited<br />
Speaker: “Role of the F-box protein Skp2 in human breast cancer”.<br />
2005 DF/HCC Kidney Cancer Program Meeting. Invited Speaker:<br />
“Molecular analysis of renal cell carcinoma using single nucleotide<br />
polymorphisms (SNP) arrays”.<br />
2005 Brigham and Women’s Hospital. Thorn 5/6 Seminar Series. Invited<br />
Speaker: “p63 and Prostate Development”.<br />
2006 DF/HCC Kidney Cancer Program Meeting. Invited Speaker:<br />
“Genome-wide analysis of genetic alterations in clear cell carcinoma<br />
of the kidney”.<br />
2006 Beth Israel Deaconess Medical Center. GU Data Club. Invited<br />
Speaker. “p63 in genitourinary development”.<br />
2007 DF/HCC Kidney Cancer Program Meeting. Invited Speaker:<br />
“Development of Clinically Relevant Mouse Orthotopic Xenografts of<br />
Human Renal Cell Carcinoma”.<br />
2008 DF/HCC Kidney Cancer Program Meeting. Invited Speaker:<br />
“Mouse Orthotopic Xenografts of Human Renal Cell Carcinoma”.<br />
2009 Harvard Urology and Prostate Cancer Research Seminar Series.<br />
Invited Speaker: “p63 and Prostate Cell Lineages”.<br />
2009 Brigham and Women’s Hospital. Thorn 5/6 Seminar Series. Invited<br />
Speaker: “Non-Random Genetic Abnormalities in Kidney Cancer”<br />
2009 Dana-Farber Cancer Institute. Seminars in Genitourinary Oncology.<br />
Invited speaker: “Defining cell lineages in the prostate epithelium”.<br />
2009 Harvard Stem Cell Institute Retreat. Invited speaker:<br />
“Identification of stem cells in prostate and bladder epithelia”.<br />
2010 Brigham and Women’s Hospital. Surgical Pathology Updates Seminar<br />
Series. Invited Speaker: “Molecular Pathology of Kidney Cancer”.<br />
2010 Brigham and Women’s Hospital. Thorn 5/6 Seminar Series. Invited<br />
Speaker: “Molecular Characterization of Kidney Cancer”<br />
2011 2011 DF/HCC Kidney Cancer Program Retreat. Invited Speaker:<br />
“Orthotopic Xenografts of RCC retain histological,<br />
immunophenotypic and genetic features of tumors in patients”.<br />
Continuing Medical Education<br />
2006 Harvard Medical School, Department of Continuing Education.<br />
Regional Renal Cancer Symposium: Recent Advances in the Biology<br />
and Treatment of Renal Cell Carcinoma. Invited Speaker: “Renal<br />
Cancer Pathology and Tissue Banking”.<br />
Advisory And Supervisory Responsibilities In Laboratory Setting<br />
2003- Supervising research activities of Post-doctoral Fellows and College<br />
Graduates. 30 hours/week<br />
2006; 2010 Mentor. The DF/HCC Continuing Umbrella of Research Experiences<br />
8
2007-2009<br />
(CURE) Program. 6 hours/week<br />
Mentor. Brigham and Women’s Hospital Student Success Jobs<br />
Program. 6 hours/week<br />
2. Regional, National and International Contributions<br />
Regional presentations<br />
1997 University of Rome, Rome, Italy. Invited lecture: “Antigen receptor<br />
genes analysis in the diagnosis of cutaneous.lymphomas”.<br />
1998 Istituto Dermopatico dell’Immacolata, Rome, Italy. Continuing<br />
medical education course: “Melanocytic nevi: histological features”.<br />
1998 Istituto Dermopatico dell’Immacolata, Rome, Italy. Invited lecture:<br />
“Detection of clonal T-cell receptor gene rearrangements by PCR-<br />
SSCP analysis”.<br />
2007 University of Massachusetts Medical School, Genitourinary Program<br />
Seminars. Invited lecture: “p63 in genitourinary development”.<br />
National presentations<br />
2002 Prouts Neck Prostate Cancer Meeting. Invited lecture: The basal cell<br />
marker p63 and prostate stem cells.<br />
2006 14 th Annual SPORE Investigators’ Workshop, GU (Renal) Breakout<br />
Session. Invited lecture: “Predictive markers for response to CCI-779,<br />
IL-2, and sorafenib”.<br />
2006 2006 AUA/SBUR Summer Research Conference. Invited lecture: “p63<br />
in bladder development”.<br />
2006 Basic Research in Interstitial Cystitis: Second Investigators’ Meeting<br />
(NIH/NIDDK). Guest Speaker. “p63 in the development of the<br />
urothelium”.<br />
2006 NCI-Sponsored Renal Cancer Biomarkers Workshop. Organizer and<br />
Invited Speaker. “Preparation and use of RCC Tissue Microarrays”.<br />
2007 15 th Annual SPORE Investigators’ Workshop, GU (Renal) Breakout<br />
Session. Invited lecture: “Report on the NCI-Sponsored Renal Cancer<br />
Biomarkers Workshop”.<br />
2008 Cambridge Conference on Innovations and Challenges in Renal<br />
Cancer. Invited lecture: “Tissue Biomarkers in Renal Cell Carcinoma:<br />
Issues and Solutions"<br />
International presentations<br />
2000 International Academy of Pathology, Alghero, Italy. Invited lecture:<br />
“The use of laser capture microdissection (LCM) in molecular<br />
pathology”.<br />
2004 5 th World Congress on Urological Research, London, UK. Invited<br />
lecture: “Defining progenitor cells in the prostate epithelium”.<br />
2006 The Kidney Cancer Association’s Fifth International Kidney Cancer<br />
Symposium. Invited lecture: “Predictive markers of response to<br />
therapy for advanced renal cancer”.<br />
9
2007 CAIX Symposium- Brussels, Belgium. Invited lecture: “CAIX<br />
Expression as a Biomarker in Renal Cancer”.<br />
2008 2008 Prostate Cancer Research Foundation Forum, Toronto, Canada.<br />
Invited lecture: “Lineage commitment in prostate development”.<br />
2009 2009 ASCO Annual Meeting, Orlando, FL. Invited lecture: “Tumor<br />
biology to predict response and resistance in renal carcinoma”.<br />
E. Report of clinical activities:<br />
1. Field: Dermatopathology. Teaching hospital: Staff pathologist, Istituto<br />
Dermopatico dell’Immacolata (1993-1995; 1998).<br />
2. Patient load: 30,000 surgical pathology cases/year (1993-1995; 1998). 500<br />
molecular diagnostic cases/year (1996-1997).<br />
3. Clinical contributions:<br />
1998 Development of a PCR-based methodology for TCR gene<br />
rearrangement analysis in paraffin-embedded tissue, extensively used<br />
in routine clinical practice.<br />
2000 Identification of p63 as a reliable marker of prostate basal cells that is<br />
not expressed in prostate carcinoma. p63 immunohistochemistry is<br />
currently used in routine clinical practice for the diagnosis of<br />
challenging prostate biopsies.<br />
10
<strong>Part</strong> III Bibliography<br />
Original Articles<br />
1. Di Tondo U, Ciardi A, Pecorella I, Signoretti S, Taccogna S, Berloco P, Cinti P, Caricato M,<br />
Iappelli M Alfani D, Cortesini R. Postoperative liver transplant monitoring with fine-needle<br />
aspiration biopsy. Transplant Proc. 1989;21:2311-12.<br />
2. Muhlhauser J, Jones M, Yamada I, Cirielli C, Lemarchand P, Gloe TR, Bewig B, Signoretti<br />
S, Crystal RG, Capogrossi MC: Safety and efficacy of in vivo gene transfer into the porcine<br />
heart with replication-deficient, recombinant adenovirus vectors. Gene Ther. 1996;3:145-53.<br />
3. Benucci R, Annessi G, Signoretti S, Simoni R: Minimally differentiated acute myeloid<br />
leukaemia revealed by specific cutaneous lesions. Brit J Dermatol. 1996;135:119-23.<br />
4. Signoretti S, Annessi G, Occhiuto S, Ruatti P, Faraggiana T: Papular clear cell hyperplasia<br />
of the eccrine duct in a diabetic. Brit J Dermatol. 1996;135:139-43.<br />
5. Annessi G, Signoretti S, Angelo C, Paradisi M, Puddu P: Neutrophilic figurate erythema of<br />
infancy. Am J Dermatopathol. 1997;19:403-06.<br />
6. Cerroni L, Signoretti S, Hofler G, Annessi G, Putz B, Lackinger E, Metze D, Giannetti A,<br />
Kerl H: Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of<br />
low-grade malignant cutaneous B-cell lymphoma. Am J Surg Pathol. 1997;21:1307-15.<br />
7. Singh SP, Lipman J, Goldman H, Ellis FH Jr, Aizenman L, Cangi MG, Signoretti S, Chiaur<br />
DS, Pagano M, Loda M.: Loss or altered subcellular localization of p27 in Barrett's<br />
associated adenocarcinoma. Cancer Res. 1998;58:1730-35.<br />
8. Ascoli V, Nardi F, Carnovale Scalzo C, Signoretti S, Pistilli A, Lo Coco F. Absence of<br />
HHV-8 sequences in malignant mesotelioma. Mol Pathol, 1998;51:113-14.<br />
9. Signoretti S, Annessi G. Are histopathological attributes of nevi and melanomas on volar<br />
skin related to skin markings? Dermatopathology: practical and conceptual. 1998;4:311-313.<br />
10. Signoretti S, Annessi G, Puddu P, Faraggiana T: Melanocytic Nevi of palms and soles: a<br />
histological study according to the plane of section. Am J Surg Pathol. 1999;23:283-7.<br />
11. Signoretti S, Murphy M, Cangi MG, Puddu P, Kadin ME, M. Loda. Detection of clonal Tcell<br />
receptor gene rearrangements by PCR and non-radioactive single strand<br />
conformational polymorphism (SSCP) analysis. Am J Pathol. 1999;154:67-75.<br />
12. Murphy M, Signoretti S, Nasser I, Sherburne B, Loda M. Detection of concurrent/recurrent<br />
non-Hodgkin lymphomas in effusions by PCR. Hum Pathol. 1999;30:1361-6.<br />
13. Signoretti S, Murphy M, Puddu P, DeCoteau JF, Faraggiana T, Kadin ME, Loda M.<br />
Improved detection of B-cell clonality by microdissection and PCR-IgH gene rearrangement<br />
analysis in the diagnosis of cutaneous B-cell infiltrates. Diag Mol Pathol. 1999;4:176-82.<br />
14. Murphy M, Signoretti S, Kadin ME, Loda M. Detection of TCR- gene rearrangements in<br />
early mycosis fungoides by non-radioactive PCR-SSCP. J Cut Pathol. 2000;27:228-34.<br />
11
15. Narducci MG, Pescarmona E, Lazzeri C, Signoretti S, Lavinia AM, Remotti D, Scala E,<br />
Baroni CD, Stoppacciaro A, Croce CM, Russo G. Regulation of TCL1 expression in B- and<br />
T-cell lymphomas and reactive lymphoid tissues. Cancer Res. 2000;60:2095-100.<br />
16. Cangi MG, Cukor B, Soung P, Signoretti S, Moreira G, Ranashinge M, Cady B, Pagano M,<br />
Loda M. Role of the cdc25A phosphatase in human breast cancer. J Clin Invest. 2000;106:<br />
753-61.<br />
17. Gesbert F, Sellers WR, Signoretti S, Loda M, Griffin JD. Bcr/Abl regulates expression of<br />
the cyclin dependent kinase inhibitor p27 kip1 through the PI3K/Akt pathway. J Biol Chem.<br />
2000;275:39223-30.<br />
18. Signoretti S, Montironi R Manola J, Altimari A, Tam C, Bubley G, Balk S, Thomas G,<br />
Kaplan I, Hlatky L, Hahnfeldt P, Kantoff P, Loda M. Her-2-neu expression and androgen<br />
independence in human prostate cancer. J Natl Cancer Inst. 2000;92:1918-25.<br />
19. Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, McKeon F,<br />
Montironi R, Loda M. p63 is a prostate basal cell marker and is required for prostate<br />
development. Am J Pathol. 2000;157:1769-75.<br />
20. Nokamura N, Ramaswamy S, Vazquez, Signoretti S, Loda M, Sellers WR. Forkhead<br />
transcription factors are critical effectors of cell death and cell cycle arrest downstream of<br />
PTEN. Mol Cell Biol. 2000;20:8969-82.<br />
21. Ascoli V, Signoretti S, Onetti Muda A, Della Rocca C, Mastroianni C M, Gastaldi R,<br />
Pescarmona E, Nardi F, Gaidiana G, Carbone A, Lo Coco F. Primary effusion lymphoma in<br />
HIV-infected patients with multicentric Castleman’s disease. J Pathol. 2001;193:200-9.<br />
22. Datta MW, Macri’ E, Signoretti S, Renshaw A A, Loda M. Transition from in situ to<br />
invasive testicular germ cell neoplasia is characterized by the loss of p21 and gain of mdm-2<br />
expression. Mod Pathol. 2001;14:437-42.<br />
23. Waltregny D, Leav I, Signoretti S, Soung P, Lin D, Merk F, Adam YA, Bhattacharya N,<br />
Cirenei N, Loda M. Androgen-driven prostate epithelial cell proliferation and differentiation<br />
in vivo involve the regulation of p27 kip1 through its proteasome-mediated degradation. Mol<br />
Endocrinol. 2001;15:765-82.<br />
24. Di Rienzo J, Signoretti S, Nakamura N, Rivera-Gonzales R, Sellers WR, Loda M, Brown M.<br />
Growth factor requirement and basal phenotype of immortalized mammary epithelial cells.<br />
Cancer Res. 2002 Jan 1;62(1):89-98.<br />
25. Bardeesy N, Morgan J, Sinha M, Signoretti S, Srivastava S, Loda M, Merlino G, DePinho<br />
RA. Obligate role for p16 Ink4a and p19 arf -p53 in murine pancreatic neoplasia. Mol Cell Biol.<br />
2002;22:635-43.<br />
26. Lindeman N, Waltregny D, Signoretti S, Loda M. Gene transcript quantitation by real time<br />
RT-PCR in cells selected by immunohistochemistry-laser capture microdissection. Diag Mol<br />
Pathol. 2002;4:187-92.<br />
27. Gounari F, Signoretti S, Klein L, Bronson R, Sellers WR, Kum J, Siermann A, Taketo MM,<br />
von Boehmer H, Khazaie K. Stabilization of -Catenin induces prostatic intraepithalial<br />
12
neoplasia, but terminal squamous transdifferetiation of other secretory epithelia. Oncogene.<br />
2002;21:4099-107.<br />
28. Signoretti S, di Marcotullio L, Richardson A, Ramaswamy S, Carrano A C, Isaac B, Rue M,<br />
Monti F, Loda M and Pagano M. Oncogenic role of the ubiquitin ligase subunit Skp2 in<br />
human breast cancer. J Clin Invest. 2002;110:633-41.<br />
29. Bardeesy N, Sinha M, Hezel A F, Signoretti S, Hathaway N A, Sharpless N E, Loda M,<br />
Carrasco D R and DePinho RA. Loss of the Lkb1 tumor suppressor provokes intestinal<br />
polyposis but resistance to transformation. Nature. 2002;419:162-7.<br />
30. Weinstein MH, Signoretti S, Loda M. Diagnostic utility of immunohistochemical staining<br />
for p63, a sensitive marker of prostatic basal cells. Mod Pathol. 2002;12:1302-1308.<br />
31. Garraway LA, Lin D, Signoretti S, Waltregny D, Dilks J, Bhattacharya N, Loda M.<br />
Intermediate Basal Cells of the Prostate: In Vitro and In Vivo Characterization. Prostate.<br />
2003;15:206-18.<br />
32. Graner E, Tang D, Rossi S, Baron A, Migita T, Weinstein LJ, Lechpammer M, Huesken D,<br />
Zimmermeann J, Signoretti S, Loda M. The isopeptidase USP2a regulates the stability of<br />
Fatty Acid Synthase in prostate cancer. Cancer Cell. 2004; 5:253-61.<br />
33. Murphy M, Carlson JA, Keough MP, Claffey KP, Signoretti S, Loda M. Hypoxia regulation<br />
of the cell cycle in malignant melanoma: putative role for the cyclin dependent kinase<br />
inhibitor p27. J Cutan Pathol. 2004;31:477-82.<br />
34. Berger R, Febbo PG, Majumder PK , Zhao J, Mukherjee S, Signoretti S, Campbell KT,<br />
Sellers WR, Roberts TM, Loda M, Golub TR, Hahn WC. Androgen-induced differentiation<br />
and tumorigenicity of human prostate epithelial cells. Cancer Res. 2004; 64:8867-75.<br />
35. Horkan C, Dalal K, Coderre JA, Kiger JL, Dupuy DE, Signoretti S, Goldberg SN. Tumor<br />
ablation: reduced tumor growth with combined radiofrequency ablation and radiation therapy<br />
in a rat breast tumor model. Radiology. 2005;235(1):81-8.<br />
36. Atkins MB, Regan M, McDermott D, Mier J, Stanbridge E, Youmans A, Febbo P, Upton M,<br />
Lechpammer M, Signoretti S. Carbonic Anhydrase IX Expression Predicts Outcome of IL-2<br />
Therapy. Clin Cancer Res. 2005; 11:3714-21.<br />
37. Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Zabaleta J, Quiceno D, Signoretti S,<br />
McDermott D, Youmans A, O’Neill A, Regan M, Mier J, Ochoa AC. Suppressor Myeloid<br />
Cells in Renal Cell Carcinoma Block T Cell Function and z Chain Expression. Cancer Res.<br />
2005; 65:3044-8.<br />
38. Ahmed M, Liu Z, Lukyanov AN, Signoretti S, Horkan C, Monsky WL, Torchilin VP,<br />
Goldberg SN. Combination radiofrequency ablation with intratumoral liposomal<br />
doxorubicin: effect on drug accumulation and coagulation in multiple tissues and tumor types<br />
in animals. Radiology. 2005; 235:469-77.<br />
39. Luo J, Sobkiw CL, Logsdon NM, Watt JM, Signoretti S, O'connell F, Shin E, Shim Y, Pao<br />
L, Neel BG, Depinho RA, Loda M, Cantley LC. Modulation of epithelial neoplasia and<br />
lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide<br />
3-kinase. Proc Natl Acad Sci (U S A). 2005; 102:10238-43.<br />
13
40. Signoretti S*, Pires MM, Lindauer M, Horner JW, Grisanzio C, Dhar S, Majumder P,<br />
McKeon F, Kantoff PW, Sellers WR, Loda M*. p63 regulates commitment to the epithelial<br />
cell lineage. Proc Natl Acad Sci (U S A). 2005; 102:11355-60.<br />
41. De Marzo AM, Platz EA, Epstein JI, Ali T, Billis A, Chan TY, Cheng L, Datta M, Egevad L,<br />
Ertoy-Baydar D, Farre X, Fine SW, Iczkowski K A, Ittmann M, Knudsen S, Loda M, Lopez-<br />
Beltran A, Magi-Galluzzi C, Mikuz G, Montironi R, Pikarsky E, Pizov G, Rubin M A,<br />
Samaratunga H, Sebo T, Sesterhenn IA, Shah RB, Signoretti S, Simko J, Thomas G,<br />
Troncoso P, Tsuzuki TT, van Leenders GJ, Yang XJ, Zhou M, Figg WD, Hoque A and Lucia<br />
MS. A working group classification of focal prostate atrophy lesions. Am J Surg Pathol.<br />
2006; 30(10):1281-91.<br />
42. Berger R, Lin DI, Nieto, Sicinska Ewa, L. Garraway LA, Heiner A, Signoretti S, Hahn WC<br />
and Loda M. Androgen-dependent regulation of Her-2/neu In Prostate Cancer Cells. Cancer<br />
Res. 2006; 66:5723-8.<br />
43. Hines-Peralta A, Sukhatme V, Regan M, Signoretti S, Liu ZJ, Goldberg SN. Improved<br />
Tumor Destruction with Arsenic Trioxide and Radiofrequency Ablation in Three Animal<br />
Models. Radiology. 2006; 240(1):82-9.<br />
44. Hakime A, Hines-Peralta A, Peddi H,. Atkins MB, Sukhatme VP, Signoretti S, Regan M,<br />
and Goldberg SN. Combination of radiofrequency with antiagiogenic therapy increases<br />
tumor ablation efficacy. Radiology. 2007; 244(2):464-70.<br />
45. Zhan Q, Signoretti S, Whitaker-Menezes D, Friedman TM, Korngold R and Murphy GF.<br />
Cytokeratin15-Positive Basal Epithelial Cells Targeted in Graft-Versus-Host Disease<br />
Express a Constitutive Antiapoptotic Phenotype. J Invest Dermatol. 2006; 27(1):106-15.<br />
46. Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng<br />
W, Zander T, Macconnaill LE, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L,<br />
Majmudar K, Ziaugra L, Wong KK, Gabriel S, Beroukhim R, Peyton M, Barretina J, Dutt A,<br />
Emery C, Greulich H, Shah K, Sasaki H, Gazdar A, Minna J, Armstrong SA, Mellinghoff IK,<br />
Hodi FS, Dranoff G, Mischel PS, Cloughesy TF, Nelson SF, Liau LM, Mertz K, Rubin MA,<br />
Moch H, Loda M, Catalona W, Fletcher J, Signoretti S, Kaye F, Anderson KC, Demetri GD,<br />
Dummer R,Wagner S, Herlyn M, Sellers WR, Meyerson M, Garraway LA. High-throughput<br />
oncogene mutation profiling in human cancer. Nat Genet. 2007; 39(3):347-51.<br />
47. Cho D, Signoretti S, Dabora S, Regan M, Seeley A, Mariotti M, Youmans A,<br />
Polivy A, Mandato L, McDermott D, Stanbridge E, Atkins M. Potential<br />
histologic and molecular predictors of response to temsirolimus in<br />
patients with advanced renal cell carcinoma. Clin Genitourin Cancer.<br />
2007;5(6):379-85.<br />
48. Sabir A, Schor-Bardach R, Wilcox CJ, Rahmanuddin S, Atkins MB, Kruskal JB, Signoretti<br />
S, Raptopoulos VD, Goldberg SN. Perfusion MDCT enables early detection of therapeutic<br />
response to antiangiogenic therapy. AJR Am J Roentgenol. 2008 Jul;191(1):133-9.<br />
49. Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, Signoretti S, Kaelin<br />
WG Jr. Acute Loss of pVHL Actuates a HIF-independent Senescence Program Mediated by<br />
pRb and p400. Nat Cell Biol. 2008; 10(3):361-9.<br />
14
50. Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, Zhang J, Signoretti S, Loda M, Roberts TM,<br />
and Zhao JJ. Kinase-dependent and -independent roles of PI3K-p110β in cell growth,<br />
metabolism and tumorigenesis. Nature. 2008;454(7205):776-9.<br />
51. Majumder P, Grisanzio C, O’Connell F, Xu Q, Berger R, Herman P, Bikoff R, Baek WK,<br />
Wang S, Ellwood-Yen K, Hahn WC, Wu H, Sawyers CL, Signoretti S, Loda M, Sellers WR.<br />
A prostatic intraepithelial neoplasia-dependent p27kip1 checkpoint induces senescence,<br />
inhibits cell proliferation and cancer progression. Cancer Cell. 2008;14(2):146-55.<br />
52. Hulick P, Zimmer M, Margulis V, Skates S, Hamel M, Dahl M. D, Michaelson D,<br />
Liebermann T, Signoretti S, Carney W, Wood C, Iliopoulos O. Blood Levels of Carbonic<br />
Anhydrase 9 Correlate with Clear Cell Renal Cell Carcinoma Activity. Clin Proteom. 2009;<br />
5:37-45.<br />
53. Xie H, Valera VA, Merino MJ, Amato AM, Signoretti S, Linehan WM, Sukhatme VP, Seth<br />
P. LDH-A Inhibition, a therapeutic strategy for treatment of Hereditary Leiomyomatosis and<br />
Renal Cell Cancer (HLRCC). Mol Cancer Ther. 2009;8(3):626-35.<br />
54. Migita T, Ruiz S, Fornari A, Inazuka F, Fiorentino M, Zadra G, Grisanzio C, Palescandolo E,<br />
Priolo C, Shin E, Fiore C, Xie W, Kung A, Febbo P, Subramanian A, Mucci L, Ma J,<br />
Signoretti S, Stampfer M, Hahn W, Finn S, Loda M. Fatty Acid Synthase: A Metabolic<br />
Enzyme and Candidate Oncogene in Prostate Cancer. J Natl Cancer Inst. 2009;101(7):519-<br />
32.<br />
55. Walker SR, Nelson EA, Zou L, Chaudhury M, Signoretti S, Richardson A, Frank DA.<br />
Reciprocal effects of STAT5 and STAT3 in breast cancer. Mol Cancer Res. 2009 Jun 2.<br />
[Epub ahead of print].<br />
56. Wiklund F, Tretli S, Choueiri TK, Signoretti S, Fall K, Adami HO. The risk of bilateral<br />
renal cell cancer. J Clin Oncol. 2009;27:3737-41.<br />
57. Schor-Bardach R, Alsop DC, Pedrosa I, Solazzo SA, Wang X, Marquis RP, Atkins MB,<br />
Regan M, Signoretti S, Lenkinski RE, Goldberg SN. Does Arterial Spin-labeling MR<br />
Imaging–Measured Tumor Perfusion Correlate with Renal Cell Cancer Response to<br />
Antiangiogenic Therapy in a Mouse Model? Radiology. 2009;251(3):731-42.<br />
58. Beroukhim R, Brunet JP, Di Napoli A, Mertz KD, Seeley A, Pires MM, Linhart D, Worrell<br />
RA, Moch H, Rubin, RA, Sellers WR, Meyerson M, W Linehan M, Rubin M, Kaelin WG,<br />
Signoretti S. Patterns of gene expression and copy-number alterations in VHL diseaseassociated<br />
and sporadic clear cell carcinoma of the kidney. Cancer Res. 2009;69(11):4674-<br />
81.<br />
59. Sabbisetti S, Di Napoli A, Seeley A, Amato AM, O’Regan E, Ghebremichael M, Loda M,<br />
Signoretti S. p63 Promotes Cell Survival Through Fatty Acid Synthase. PLoS ONE.<br />
2009;4(6):e5877.<br />
60. Solazzo SA, Ahmed M, Schor-Bardach R, Yang W, Girnun GD, Rahmanuddin S, Levchenko<br />
T, Signoretti S, Spitz DR, Torchilin V, Goldberg SN. Liposomal Doxorubicin Increases<br />
Radiofrequency Ablation-induced Tumor Destruction by Increasing Cellular Oxidative and<br />
Nitrative Stress and Accelerating Apoptotic Pathways. Radiology. 2010 255(1):62-74.<br />
15
61. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J,<br />
Boehm JS, Dobson J, Urashima M, McHenry K, Pinchback R, Ligon AH, Cho J, Haery L,<br />
Greulich H, Reich M, Winckler W, Weir BA, Tanaka K, Chiang DY, Bass AJ, Loo A,<br />
Hoffman C, Prensner J, Liefeld T, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H,<br />
Tepper JE, Fletcher JA, Baselga J, Tsao M, Rubin MA, Janne PA, Daly MJ, Nucera C,<br />
Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway<br />
LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Lander ES, Getz G,<br />
Golub TR, Sellers WR, Meyerson M. The landscape of copy number alterations across<br />
multiple human cancers. Nature. 2010;463:899-905.<br />
62. Choueiri TK, Regan MM, Rosenberg JE, Oh WK, Clement J, Amato AM, McDermott D,<br />
Cho DC, Atkins MB, Signoretti S. Carbonic anhydrase IX (CAIX) and pathologic features<br />
as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving<br />
VEGF-targeted therapy. BJU Int. 2010;106(6):772-8.<br />
63. Lee SH, Poulogiannis G, Pyne S, Jia S, Zou L, Signoretti S, Loda M, Cantley LC, and<br />
Roberts TM. A constitutively activated form of the p110β isoform of PI3-kinase induces<br />
prostatic intraepithelial neoplasia in mice. Proc Natl Acad Sci (U S A). 2010;107(24):11002-<br />
7.<br />
64. Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, Signoretti S,<br />
Mier JW. The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235<br />
Compared to Rapamycin in Renal Cell Carcinoma. Clin Cancer Res. 2010;16(14):3628-38.<br />
65. Yang W, Ahmed M, Elian M, Hady ES, Levchenko TS, Sawant RR, Signoretti S, Collins M,<br />
Torchilin VP, Goldberg SN. Do Liposomal Apoptotic Enhancers IncreaseTumor Coagulation<br />
and End-Point Survival in Percutaneous Radiofrequency Ablation of Tumors in a Rat Tumor<br />
Model? Radiology 2010 Sep 21. [Epub ahead of print].<br />
66. Genega, EM, Ghebremichael, M, Najarian R, Fu Y, Wang, Y, Argani, P, Grisanzio, C,<br />
Signoretti S. CAIX Expression in Renal Neoplasms: Correlation with Tumor Type and<br />
Grade. Am J Clin Pathol. 2010;134(6):873-9.<br />
67. Bhatt R, Wang X, Zhang L, Collins M, Signoretti S, Alsop D, Goldberg SN, Atkins MB,<br />
Mier JW. Renal cancer resistance to antiangiogenic therapy is delayed by restoration of<br />
angiostatic signaling. Mol Cancer Ther. 2010:9(10):2793-802.<br />
68. Moslehi J, Minamishima YA, Padera RF, Signoretti S, Liao R, and Kaelin WG. Loss of<br />
PHD Prolyl Hydroxylase Activity in Cardiomyocytes Phenocopies Ischemic<br />
Cardiomyopathy. Circulation. 2010;122(10):1004-16.<br />
69. Gan B, Lim C, Chu G, Hua S, Ding Z,Collins M, Hu J, Jiang S, Fletcher-Sananikone E,<br />
Zhuang L, Chang M, Zheng H, Wang YA, Kwiatkowski DJ, Kaelin WG, Signoretti S and<br />
DePinho RA. FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal<br />
tumorigenesis. Cancer Cell. 2010;18(5):472-84.<br />
70. Ding Z, Wu C, Chu GC, Xiao Y, Ho D, Zhang J, Perry SR, Labrot ES, Wu X, Lis R, Hoshida<br />
Y, Hiller D, Hu B, Jiang S, Zheng H, Stegh AH, Scott AL, Signoretti S, El-Bardeesy NM,<br />
Wang YA, Hill D, Golub TR, Stampfer MJ, Wong WH, Loda M, Mucci L, Chin L &<br />
DePinho RA. SMAD4-dependent barrier constrains prostate cancer growth and metastatic<br />
progression. Nature. 2011;470(7333):269-73.<br />
16
71. Bernardi R, Papa A, Egia A, Coltella N, Teruya-Feldstein J, Signoretti S and Pandolfi PP.<br />
Pml represses tumor progression through inhibition of mTOR. EMBO Mol Med.<br />
2011;3(5):249-57.<br />
72. Flavin R, Finn SP, Choueiri TK, Ingoldsby H, Ring M, Barrett C, Rogers M, Smyth P,<br />
O'Regan E, Gaffney E, O'Leary JJ, Loda M, Signoretti S, Sheils O. RET protein expression<br />
in papillary renal cell carcinoma. Urol Oncol. 2011 Mar 9. [Epub ahead of print].<br />
73. Lee SH, Jia S, Zhu Y, Utermark T, Signoretti S, Loda M, Schaffhausen B, Roberts TM.<br />
Transgenic expression of polyoma virus middle T antigen in the mouse prostate gives rise to<br />
carcinoma. J Virol. 2011;85(11):5581-92.<br />
74. Zhang L, Bhasin M, Schor-Bardach; R, Wang X, Collins MP, Panka D, Putheti P, Signoretti<br />
S, Alsop DC, Libermann T, Atkins MB, Mier JW, Goldberg NS, Bhatt RS. Resistance of<br />
renal cell carcinoma to sorafenib is mediated by potentially reversible gene expression. PLoS<br />
ONE. 2011;6(4):e19144.<br />
75. Grisanzio C, Seeley A, Chang M, Collins M, Di Napoli A, Cheng SC, Percy A, Beroukhim<br />
R, Signoretti S. Orthotopic xenografts of RCC retain histological, immunophenotypic and<br />
genetic features of tumors in patients. J Pathol. 2011 May 2. [Epub ahead of print].<br />
76. Shen C, Beroukhim R, Schumacher S, Zhou J, Chang M, Signoretti S, and Kaelin WG.<br />
Genetic and Functional Studies Implicate HIF1alpha as a 14q Kidney Cancer Suppressor<br />
Gene. Cancer Discovery. 2011;1:222-235<br />
77. Lin W, Cao J, Liu J, Beshiri ML, Fujiwara Y, Francis J, Cherniack AD, Geisen C, Blair LP,<br />
Zou MR, Shen X, Kawamori D, Liu Z, Grisanzio C, Watanabe H, Minamishima YA, Zhang<br />
Q, Kulkarni RN, Signoretti S, Rodig SJ, Bronson RT, Orkin SH, Tuck DP, Benevolenskaya<br />
EV, Meyerson M, Kaelin WG, and Yan Q. Loss of the RBP2 histone demethylase suppresses<br />
tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci (U S A). 2011;108:13379-<br />
86.<br />
78. Yang W, Ahmed M, Tasawwar B, Levchenko T, Sawant RR, Collins M, Signoretti S,<br />
Torchilin V, Goldberg SN. Radiofrequency ablation combined with liposomal quercetin to<br />
increase tumour destruction by modulation of heat shock protein production in a small<br />
animal model. Int J Hyperthermia. 2011;27(6):527-38.<br />
79. Bass AJ, Lawrence MS, Brace LE, Ramos AH, Drier Y, Cibulskis K, Sougnez C, Voet D,<br />
Saksena G, Sivachenko A, Jing R, Parkin M, Pugh T, Verhaak RG, Stransky N, Boutin AT,<br />
Barretina J, Solit DB, Vakiani E, Shao W, Mishina Y, Warmuth M, Jimenez J, Chiang DY,<br />
Signoretti S, Kaelin WG, Spardy N, Hahn WC, Hoshida Y, Ogino S, Depinho RA, Chin L,<br />
Garraway LA, Fuchs CS, Baselga J, Tabernero J, Gabriel S, Lander ES, Getz G, Meyerson<br />
M. Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-<br />
TCF7L2 fusion. Nat Genet. 2011 Sep 4 [Epub ahead of print].<br />
* Co-corresponding authors.<br />
Review Articles and Editorials<br />
1. Signoretti S, Loda M. Estrogen receptor beta in prostate cancer: brake pedal or accelerator?<br />
Am J Pathol 2001;159:13-6.<br />
17
2. Signoretti S and Loda M. Defining stem cells in the prostate epithelium. Cell Cycle. 2006;<br />
5:138-41.<br />
3. Cho D, Signoretti S, Regan M, Mier JW, Atkins MB. The role of mammalian target of<br />
rapamycin inhibitors in the treatment of advanced renal cancer. Clin Cancer Res. 2007;13(2<br />
Pt 2):758s-763s.<br />
4. Signoretti S and Loda M. Prostate stem cells: from development to cancer. Semin Cancer<br />
Biol. 2007; 17(3):219-24.<br />
5. Grisanzio C and Signoretti S. p63 in prostate biology and pathology. J Cell Biochem. 2008;<br />
103(5):1354-68.<br />
6. Signoretti S, Regan M, Atkins MB. Carbonic Anhydrase IX (CAIX) as a predictive<br />
biomarker of response to kidney cancer therapy. BJU Int. 2008; 101 Suppl 4:31-5.<br />
7. Signoretti S, Bratslavsky G, Waldman FM, Reuter VE, Haaga J, Merino M, Thomas GV,<br />
Pins MR, Libermann T, Gillespie J, Tomaszewski JE, Compton CC, Hruszkewycz A,<br />
Linehan WM, Atkins MB. Tissue-Based Research In Kidney Cancer: Current Challenges<br />
And Future Directions. Clin Cancer Res. 2008;14(12):3699-705.<br />
8. Signoretti S. Tissue-Based Research in the Era of ‘Personalized Medicine’: Biomarkers,<br />
Microarrays, and Beyond. Kidney Cancer Journal. 2008;235-9.<br />
9. Di Napoli A and Signoretti S. Tissue Biomarkers in Renal Cell Carcinoma: Issues and<br />
Solutions. Cancer. 2009;115(10 Suppl):2290-7.<br />
10. Atkins MB, Choueiri TK, Cho D, Regan M, Signoretti S. Treatment Selection for Patients<br />
With Metastatic Renal Cell Carcinoma. Cancer. 2009;115(10 Suppl):2327-33.<br />
11. Atkins MB, Bukowski RM, Escudier BJ, Figlin RA, Hudes GH, Kaelin WG Jr, Linehan<br />
WM, McDermott DF, Mier JW, Pedrosa I, Rini BI, Signoretti S, Sosman JA, The BT, Wood<br />
CG, Zurita, AJ and King L. Innovations and Challenges in Renal Cancer: Summary<br />
Statement From the Third Cambridge Conference. Cancer. 2009;115(10 Suppl):2247-51.<br />
Chapters in Books<br />
1. Kamino H, Signoretti S, Weedon D. Site specific nevi. In “WHO classification of tumors:<br />
Pathology and Genetics of Skin Tumors”. Edited by LeBoit PE, Burg G, Weedon D, Sarasin<br />
A.<br />
2. Grisanzio C and Signoretti S. Adult Prostate Epithelium Renewal, Stem Cells and Cancer. In<br />
“Stem Cells and Cancer”. Edited by Rebecca G. Bagley and Beverly A. Teicher. 2009.<br />
3. Bahamon B and Signoretti S. Tissue Biomarkers in Renal Cell Carcinoma: Intermediate<br />
Endpoints in the Selection of Targeted Agents for RCC. In “ Renal Cell Carcinoma:<br />
Biology, Prognostic Factors and Therapeutic Targets” . Edited by Kimryn Rathmell, Brian<br />
Rini and Robert A. Figlin. In Press.<br />
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Thesis<br />
1. M.D. Thesis: Signoretti S. Cyclosporin nephrotoxicity in kidney transplantation. University<br />
of Rome, 1988.<br />
2. Pathology Residency Thesis: Signoretti S. Congenital cystic adenomatoid, malformation of<br />
the lung. University of Rome, 1993.<br />
Patents<br />
1. 1999. Loda M, Macri’ E, Signoretti S. “Cdx-2 as a unique marker of colon carcinoma”<br />
2. 1999. Harvard Medical School, Harvard Case #1674. McKeon F, Yang A, Loda M,<br />
Signoretti S, Crum C. “p63 expression pattern in the classification of malignancies of the<br />
prostate, cervix and breast”<br />
Abstracts (Unpublished work)<br />
1. Grisanzio C, Sabbisetti V, Browne D, Signoretti S. p63 in Development and Maintenance of<br />
the Prostate Epithelium. Department of Defense Prostate Cancer Research Program Meeting.<br />
Innovative minds in Prostate Cancer Today (IMPaCT). Atlanta, Georgia 2007.<br />
2. Han WK, Hsiao L, Signoretti S, Bonventre JV, Steele G. Kidney Injury Molecule- (KIM-1)<br />
and carbonic Anhydrase IX (CAIX) as Urinary Biomarkers for Renal Cell Carcinoma. J Am<br />
Soc Nephrol. 2007; 18:222A.<br />
3. Di Napoli A, Grisanzio C, Ghebremichael M, Seeley A, Amato AM, Atkins MB, Signoretti S.<br />
CAIX Expression Correlates with VHL Mutational Status in Sporadic Clear Cell Carcinoma<br />
of the Kidney. Annual Meeting United States and Canadian Division of the International<br />
Academy of Pathology, Denver, Colorado, 2008.<br />
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