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Transcriptional Networks in Lung Cancer - Michela Garofalo

Michela completed her undergraduate degree in Biology at the University Federico II of Naples in Italy. She obtained her PhD in 2008 from the same University, in Professor G. Condorelli’s laboratory, elucidating the molecular mechanisms involved in the resistance to apoptotic cell death induction in different types of tumours. From 2008 to 2011, she trained as a Postdoctoral Fellow in Professor Carlo Croce’s laboratory at the Ohio State University, advancing the understanding of the role of non-coding RNAs in cancer progression and development. She identified several oncogenic pathways, regulated by microRNAs, involved in the cellular response to chemotherapy and metastasis in lung cancer with important consequences for the identification of potential new therapies for cancer treatment and prevention. In 2011, Michela was granted the prestigious Kimmel Award. She joined the CRUK Manchester Institute as a Junior Group Leader in July 2014.

Introduction

Lung cancer causes the most cancer-related deaths in the world and the main obstacle to a cure is chemoresistance. Main interest of our group is to identify the causes behind lung cancer development and resistance to chemotherapy. Over the last decade, a growing number of non-coding transcripts (ncRNAs) have been found to have a pivotal role in gene regulation and cell biology.

The most well- known ncRNAs are microRNAs (miRNAs), single stranded RNAs of 19–25 nucleotides in length, which negatively regulate gene expression by translational inhibition or degradation of the mRNA targets. MiRNAs are differentially expressed in almost all types of human cancers versus the normal tissue counterpart and are key players in cancer onset and progression, functioning as tumour promoters (TP) or tumour suppressors (TS). The application of miRNAs to cancer therapeutics and diagnostics is emerging as an important field of gene therapy. Thus far both miRNA replacement and miRNA inhibition strategies have been successfully used to restore normal gene networks in vitro and in vivo, evidencing the huge potential of microRNAs in the fight against cancer.

Selected Publications

Naidu S, Shi L, Magee P, Middleton JD, Laganá A, Sahoo S, Leong HS, Galvin M, Frese K, Dive C, Guzzardo V, Fassan M, Garofalo M. (2017)
PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways.
Scientific Reports 7(1):15441. PubMed abstract

Taccioli C, Garofalo M, Chen H, Jiang H, Malagoli Tagliazucchi G, Di Leva G, Alder H, Middleton J, Smalley KJ, Selmi T, Farber JL, Croce CM, Fong LYY. (2015)
Repression of esophageal neoplasia and inflammatory signaling by Anti-miR-31 delivery in vivo. Journal of the National Cancer Institute 107(11). PubMed abstract

Naidu S, Magee P, Garofalo M. (2015)
MiRNA-based therapeutic intervention of cancer.
Journal of Hematology & Oncology 8(1):68. PubMed abstract

Jeon YJ, Middleton J, Kim T, Lagana A, Piovan C, Secchiero P, Nuovo GJ, Cui R, Romano G, Di Leva G, Lee BK, Sun HL, Kim H, Alder H, Garofalo M, Croce CM. (2015)
A set of NF-KB-regulated microRNAs induces acquired TRAIL resistance in lung cancer.
Proceedings of the National Academy of Sciences of USA 112(26):E3355-64. PubMed abstract

Joshi P, Jeon YJ, Lagana A, Middleton J, Secchiero P, Garofalo M, Croce CM. (2015)
MicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC. Proceedings of the National Academy of Sciences of USA 112(28):8650-5. PubMed abstract

Garofalo M, Croce CM. (2015)
Role of microRNAs in maintaining cancer stem cells.
Advanced Drug Delivery Reviews 81:53-61. PubMed abstract

Garofalo M, Romano G, Di Leva G, Nuovo G, Jeon Y J, Ngankeu A., Sun J, Lovat F, Alder H, Condorelli G, Engelman J, Ono M, Rho JK, Cascione L, Volinia S, Nephew KP, Croce CM. (2011)
EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers.
Nature Medicine 18(1):74-82. PubMed abstract

Pichiorri F, Suh S.S, Rocci A,  De Luca L,  Taccioli C,  Ramasamy S,  Wenchao Z,  Lin HJ,  Benson D,  Hofmainster C, Garofalo M,  Di Leva G,  Volinia S,  Alder H,  Zanesi N,  Perrotti D, Kuehl M, Aqeilan RI, Palumbo A,  Croce CM. (2010)
Downregulation of p53-inducible microRNAs 192, 194 and 215 impairs p53/HDM2 autoregulatory loop in multiple myeloma development.
Cancer Cell 18(4):367-81. PubMed abstract

Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, Gasparini P, Gonelli A, Costinean S, Acunzo M, Condorelli G, Croce CM. (2009)
miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation.
Cancer Cell 16:498-509. PubMed abstract

Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, Liu CG, Croce CM, Condorelli G. (2008)
MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer.
Oncogene 27:3845-55. PubMed abstract

 

 

Team

Scientific Officer
Peter Magee

Postdoctoral Fellow
Lei Shi
Tiziana Monteverde

Graduate Students
Athanasios Paliouras
Manuela La Montagna

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