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Overview | Research directions | Group members | Awards | Grants | Ongoing Collaborations | Selected Publications

Overview

The epidemic nature of cancer renders it a highly active area of research. Given the variability of genetic patterns, it is fundamental to understand how the genetic forces responsible for the neoplastic transformation may differentially affect the aggressiveness of the disease as well as the response to treatments. My major research interest lies in the generation and study of in vitro and in vivo models carefully mirroring human tumorigenesis. Reliable models, indeed, are of paramount importance to properly investigate and correctly understand the oncogenic mechanisms associated with specific genetic alterations in human cancer, becoming an inestimable tool for the identification of effective therapeutic targets and, in turn, for the pre-clinical and co-clinical assessment of new treatment modalities.

Research directions

  • Prostate Cancer
    Few secreted factors, mainly proteins, have been characterized in human prostate cancer, but their relevance to tumor progression and response to specific treatments is not yet well understood. Our major interest lies in taking advantage of different in vitro and in vivo genetically engineered models of human prostate cancer to explore the roles of secreted molecules in prostate cancer pathogenesis, metastatic progression, and response to current standard-of-care therapies.
  • Biomarkers identification

    Prostate cancer is one of the most commonly diagnosed malignancies in men. Accurate and sufficient screening for this disease is of particular importance because prostate cancer typically does not present with any symptoms until it has become locally advanced or metastatic. Currently, there exists only one widely accepted biomarker, known as prostate-specific antigen (PSA), for use as a clinically non-invasive screen, but the efficacy of PSA as an ideal biomarker for prostate cancer has been highly debated: 1. PSA lacks specificity, elevated serum concentrations of PSA may reflect common pathological conditions such as benign prostatic hyperplasia and prostatitis; 2. PSA fails to differentiate between indolent and aggressive forms of disease likely to cause mortality.
    The identification of novel and more reliable biomarkers specifically associated with prostate cancer and able to discriminate indolent versus aggressive forms of tumour is one of the goal of our study.

  • Mechanisms of tumor progression and resistance to therapy
    We and other groups have previously demonstrated that different relevant genetically engineered mouse models of human prostate cancer achieve various stages of disease during their lifetime and show differential response to androgen depletion therapy (ADT). In this respect, a broad analysis of the tumor secretome in a panel of stage specific and androgen deprivation sensitive or resistant genetically stratified mouse models mirroring different types of human prostate cancer might represent a crucial starting point to unveil new tumorigenic pathways involved in human prostate cancer progression and ADT resistance.

  • From Bench to Bedside
    Data obtained from the secretome analysis in mouse models will be validated and integrated in human prostate cancer tissue-micro-arrays. in vitro studies on human prostate cancer cell lines will test the functional correlations between the identified secreted factors and the proliferative, migratory, and invasive ability of tumor cells, as well as the possible role of these factors in cell sensitivity/resistance to specific standard-of-care and experimental therapeutics for prostate cancer treatment. Finally, genetically engineered mouse models recapitulating some of the most common genetics of human CaP will be enrolled in pre-clinical studies testing the efficacy of targeting specific secreted factors as single therapy or in combination with standard of care treatments.

Group members

  • Andrea Lunardi, PI
  • Sacha Genovesi, Lab Manager
  • Francesco Cambuli, postdoctoral fellow
  • Marco Lorenzoni, PhD student

Post doctoral and PhD positions are currently available. Please contact andrea.lunardi [at] unitn.it

Awards

2008, Begnudelli Award, Pezcoller-AACR Foundation, Trento, Italy.

Grants

2014, Armenise/Harvard Career Development Award.

Ongoing Collaborations

Pier Paolo Pandolfi, Cancer Genetics, Harvard Medical School, USA.
Massimo Loda, Cancer Pathology, Dana Farber Cancer Institute, Harvard Medical School, USA.
Sabina Signoretti, Cancer Pathology, Brigham and Women Hospital, Harvard Medical School, USA.
Roderick Bronson, Rodent Pathology Core Facility Director, Harvard Medical School, USA.
Rodolfo Montironi, Cancer Pathology, Ospedali Riuniti, Ancona, Italy.
Wenyi Wei, Molecular and Cellular Oncology, Harvard Medical School, USA.
Enzo Galligioni, Medical Oncology, Santa Chiara Hospital, Trento, Italy.
Mattia Barbareschi, Cancer Pathology, Santa Chiara Hospital, Trento, Italy.
Orazio Caffo, Medical Oncology, Santa Chiara Hospital, Trento, Italy.
Paolo Pinton, Signal Transduction, University of Ferrara, Ferrara, Italy.
Mike Talkowski, Human Genetic, Massachusetts General Hospital, and Broad Institute, USA.

Selected publications

Articles

Lunardi A, Varmeh S, Chen M, Taulli R, Guarnerio J, Ala U, Seitzer N, Ishikawa T, Carver BS, Hobbs RM, Quarantotti V, Ng C, Berger AH, Nardella C, Poliseno L, Montironi R, Castillo-Martin M, Cordon-Cardo C, Signoretti S, Pandolfi PP. 2015. Suppression of CHK1 by ETS family members promotes DNA damage response by-pass and tumorigenesis. Cancer Discov. 2015 Feb 4. pii: CD-13-1050. PMID:25653093

Guarnerio J, Riccardi L, Taulli R, Maeda T, Wang W, Hobbs RM, Song MS, Sportoletti P, Bernardi R, Bronson RT, Castillo-Martin M, Cordon-Cardo C, Lunardi A*, Pandolfi PP*. A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells. Cancer Discov. 2015 Jan 22. pii: CD-14-1022. PMID: 25614485

Epping MT, Lunardi A, Nachmani D, Castillo-Martin M, Thin TH, Cordon-Cardo C, Pandolfi PP. Cell Death and Differentiation TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFβ signaling activation. Cell Death Differ. 2015 Jan 23. PMID:25613376

González-Billalabeitia E, Seitzer N, Song SJ, Song MS, Patnaik A, Liu XS, Epping MT, Papa A, Hobbs RM, Chen M, Lunardi A, Ng C, Webster KA, Signoretti S, Loda M, Asara JM, Nardella C, Clohessy JG, Cantley LC, Pandolfi PP. 2014. Vulnerabilities of PTEN-TP53-deficient prostate cancers to compound PARP-PI3K inhibition. Cancer Discov, 4(8): 896-904. PMID:24866151

Papa A, Wan L, Bonora M, Salmena L, Song MS, Hobbs RM, Lunardi A, Webster K, Ng C, Newton RH, Knoblauch N, Guarnerio J, Ito K, Turka LA, Beck AH, Pinton P, Bronson RT, Wei W, Pandolfi PP. 2014. Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. Cell, 157(3):595-610. PMID:24766807

Lunardi A, Webster KA, Papa A, Padmani B, Clohessy JG, Bronson RT, Pandolfi PP. 2014. Role of aberrant PI3K pathway activation in gallbladder tumorigenesis. Oncotarget, 5(4):894-900. PMID:24658595

Wang G, Lunardi A, Zhang J, Chen Z, Ala U, Webster KA, Tay Y, Gonzalez-Billalabeitia E, Egia A, Shaffer DR, Carver B, Liu XS, Taulli R, Kuo WP, Nardella C, Signoretti S, Cordon-Cardo C, Gerald WL, Pandolfi PP. 2013. Zbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion. Nat Genet, 45(7):739-46. PMID:23727861

Lunardi A, Ala U, Epping MT, Salmena L, Clohessy JG, Webster KA, Wang G, Mazzucchelli R, Bianconi M, Stack EC, Lis R, Patnaik A, Cantley LC, Bubley G, Cordon-Cardo C, Gerald WL, Montironi R, Signoretti S, Loda M, Nardella C, Pandolfi PP. 2013. A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet, 45(7):747-55. PMID:23727860

Lunardi A, Di Minin G, Provero P, Dal Ferro M, Carotti M, Del Sal G, Collavin L. 2010. A genome-scale protein interaction profile of Drosophila p53 uncovers additional nodes of the human p53 network. Proc Natl Acad Sci USA, 6;107(14):6322-7. PMID:20308539

Mauri F, McNamee LM, Lunardi A, Chiacchiera F, Del Sal G, Brodsky MH, Collavin L. 2008. Modification of Drosophila p53 by SUMO modulates its transactivation and pro-apoptotic functions. J Biol Chem, 25;283(30):20848-56. PMID:18492669

Reviews

Lunardi A, Pandolfi PP. 2014. A co-clinical platform to accelerate cancer treatment optimization. Trends Mol Med. 21(1):1-5. PMID:25466492

Lunardi A, Guarnerio J, Wang G, Maeda T, Pandolfi PP. 2013. Role of LRF/Pokemon in lineage fate decisions. Blood. 121(15):2845-53. PMID:23396304

Nardella C, Lunardi A, Patnaik A, Cantley LC, Pandolfi PP. 2011. The APL paradigm and the "co-clinical trial" project. Cancer Discov. 1(2):108-16. PMID:22116793

Collavin L, Lunardi A, Del Sal G. 2010. p53-family proteins and their regulators: hubs and spokes in tumor suppression. Cell Death Differ. Jun;17(6):901-11. PMID:20379196

Book chapters

Lunardi A, Nardella C, Clohessy JG, Pandolfi PP. 2014. Of model pets and cancer models: an introduction to mouse models of cancer. Cold Spring Harb Protoc. 1; (1):17-31. PMID:24371312