Laboratory of Stem Cells and Cancer Genomics

Overview

Adult tissue homeostasis is maintained by the accurate integration of the different signaling pathways required to preserve cell identity. Stem cell maintenance and cell lineage determination are regulated by the coordinated activity of specific signaling pathways that converge on chromatin to activate and repress well-defined transcriptional programs. By shaping the epigenomic landscape of cells, transcription factors and chromatin modifying complexes orchestrate these processes. During tumor formation driver oncogenic mutations lead to the emergence of a progenitor-like state characterized by a change in cell identity and an extensive transcriptional reprograming. This reprograming is the result of widespread rearrangement in the repertoire of active functional elements, due to alterations at different levels in their regulation: mutation in their sequence, in the expression of different transcription factors, or aberrant activity of chromatin modifying enzymes, often mutated in cancer.

In our laboratory we investigate how external and internal stimuli are integrated at the chromatin level. In particular, by using a comprehensive approach, we aim to describe the role of chromatin modifying enzymes and transcription factors in the maintenance of adult stem cells and in doing so characterize the transcriptional mechanisms and the chromatin associated events involved in tumor formation and metastatic progression. Through the extensive characterization of these mechanisms our ultimate goal is the identification of putative targets for novel pharmacological approaches.

Research Projects

Understand the transcriptional and epigenetic events driving non-alcoholic fatty liver disease (NAFLD) and liver cancer formation and progression.
Characterize the transcriptional mechanisms and chromatin modifying enzymes required to maintain intestinal stem cell identity.
Characterize the transcriptional and epigenetic mechanisms required for the growth of hepatic metastasis from colorectal cancer.
Exploit patients-derived tumor organoids as models for pre-clinical studies.

Group members

Fulvio Chiacchiera, PI
Alessandro D'Ambrosio, PhD student
Davide Bressan, PhD student
Elisa Ferracci, PhD student
Elisa Sorrenti, pre-doctoral fellow

PhD student and undergraduate student positions are available. Please contact Fulvio Chiacchiera directly

Collaborations

Prof. Guido Torzilli, Humanitas Cancer Center, Italy
Prof. Wen Xie, University of Pittsburgh, USA
Dr. Mattia Pelizzola, Italian Institute of Technology (IIT), Italy
Prof. Diego Pasini, European Institute of Oncology (IEO), Italy
Dr. Matteo Donadon, Humanitas Cancer Center, Italy
Prof. Cristiano Simone, University of Bari, Italy
Dr. Meritxell Huch, Gurdon institute, UK
Prof. Hiroshi Seno, Kyoto University, Japan

Grants

2018, MFAG, Italian Association for Cancer Research (AIRC)

Awards

2016, Begnudelli Award, Pezcoller-AACR Foundation, Trento, Italy

Selected publications

Pivetti S., Fernandez-Perez D., D’Ambrosio A., Barbieri C.M., Manganaro D., Rossi A., Barnabei L., Zanotti M., Scelfo A., Chiacchiera F.* and Pasini D.* (2019). Loss of PRC1 activity in different stem cell compartments activates a common transcriptional program with cell-type dependent outcomes. Science Advances (In press).

Chiacchiera F., Pasini D., (2017) Control of Adult Intestinal Identity by the Polycomb Repressive Machinery. Cell Cycle 16(3):243-244

Chiacchiera F.*, Rossi A., ShriGanesh J., Zanotti M., Pasini D.* (2016) PRC2 preserves intestinal progenitors and restricts secretory lineage commitment. Embo j. 35(21):2301-2314

Rossi A., Ferrari K.J., Piunti A., ShriGanesh J., Chiacchiera F., Mazzarella L., Scelfo A., Pelicci P.G., Pasini D. (2016) Maintenance of leukemic cell identity by the activity of the polycomb complex PRC1 in mice. Science Advances 2(10): e1600972

Chiacchiera F., Rossi A., ShriGanesh J., Piunti A., Scelfo A., Ordonez- Morànx P., Huelsken J., Koseki H., Pasini D. (2016) Polycomb Complex PRC1 preserves intestinal stem cell identity by sustaining Wnt/β-Catenin transcriptional activity. Cell Stem Cell, 18(1):91-103

Orfanelli U, Jachetti E, Chiacchiera F, Grioni M, Brambilla P, Briganti A, Freschi M, Martinelli-Boneschi F, Doglioni C, Montorsi F, Bellone M, Casari G, Pasini D, Lavorgna G. (2015) Antisense transcription at the TRPM2 locus as a novel prognostic marker and therapeutic target in prostate cancer. Oncogene 34(16):2094-102

Chiacchiera F., Piunti A, Pasini D. (2013) Epigenetic methylations and their connections with metabolism. Cell Mol Life Sci. 70(9):1495-508

Vella P, Scelfo A, Jammula S, Chiacchiera F, Williams K, Cuomo A, Roberto A, Christensen J, Bonaldi T, Helin K, Pasini D. (2013) Tet proteins connect the O-Linked N-acetylglucosamine Transferase Ogt to chromatin in embryonic stem cells. Mol Cell. 49(4):645-56

Chiacchiera F.*, Grossi V, Cappellari M, Peserico A, Simonatto M, Germani A, Russo S, Moyer MP, Resta N, Murzilli S, Simone C.* (2012) Blocking p38/ERK crosstalk affects colorectal cancer growth by inducing apoptosis in vitro and in preclinical mouse models. Cancer Lett. 324(1):98-108.

Chiacchiera F, Simone C., (2010) The AMPK-FoxO3A axis as a target for cancer treatment. Cell Cycle 9(6):1091-1096

Chiacchiera F, Matrone A, Ferrari E, Ingravallo G, Lo Sasso G, Murzilli S, Petruzzelli M, Salvatore L, Moschetta A, Simone C. (2009) p38alpha blockade inhibits colorectal cancer growth in vivo by inducing a switch from HIF1alpha- to FoxO-dependent transcription. Cell Death Differ. 16:1203-14.