January 2014 - December 2017: PhD in Computational Biology at European School of Molecular Medicine (SEMM), Milan, Italy.
Project title: “Genomic landscape and transcriptional regulation by Yap and Myc in the liver”
October 2010 - March 2013: Master's Degree in Medical, Molecular and Cellular Biotechnology, S. Raffaele University in Milan, Italy. Final mark: 110/110 cum laude.
Thesis title: “Functional and structural studies on the murine Sphingosine Kinase 2”
October 2007 - November 2010: Bachelor's Degree in Medical and Pharmaceutical Biotechnology, S. Raffaele University in Milan, Italy. Final mark: 110/110 cum laude.
Thesis title: “Computational analysis and structural interpretation of a missense mutation of the serum Transferrin associated with Human Congenital Hypotransferrinemia”
September 2002 - July 2007: High school leaving qualification in Chemistry, Cannizzaro Institute, Rho, Milan. Final mark: 100/100.
April 2018 - Present: Postdoctoral researcher at Italian Institute of technology (IIT), Milan, Italy.
January 2018 - March 2018: Fellowship at Italian Institute of technology (IIT), Milan, Italy.
ChroKit: a web-based framework to interactively analyze and visualize genomic data
The advent of Next-generation sequencing (NGS) technologies strongly increased our capacity to investigate the mechanisms of gene regulation at genome-wide level. However, the biological interpretation of the high amount of data produced by NGS experiments requires deep knowledge of biological systems and computational skills. Therefore, there is a growing need within the scientific community for the development of computational tools which will enable biologists to directly analyse this kind of data in a fast and intuitive way. To this end, I developed ChroKit (The Chromatin ToolKit), a web-based framework that performs comprehensive genomic analyses with an interactive and user-friendly GUI.
The program accepts, as input, a list of genomic regions of interest or a list of genes and the aligned reads from the NGS experiments (bam/wig files). These data are then elaborated to help the biologists to understand the biological system under investigation. It allows the user to perform logical operations (i.e. union, intersection and others) on genomic regions defined by selected signals (i.e. TF binding, chromatin modifications, chromatin accessible regions, nucleosome positions and others), to resize genomic regions to a user-defined width, randomly subsample regions or center them at the point of maximum enrichment (summit detection) and to perform quantitative determination of signals within the defined regions (for example, calculate the intensity of selected chromatin marks in a subset of promoters). The results of these analyses can be displayed within ChroKit using a set of visualization tools commonly used in Genomics, such as boxplots and heatmaps. Some of these plots can be easily manipulated by point and click operations, thus allowing “on the fly” re-analysis and subsetting of the regions of interests.
This application is multiplatform and can be deployed on a server to take advantage of computational resources and share data and working sessions.
ChroKit source code can be found on GitHub at https://github.com/ocroci/ChroKit
Genome-wide transcriptional regulation by YAP in the liver
YAP, a transcriptional co-factor, is the downstream regulator of the Hippo pathway. When this pathway is switched off, YAP translocates into the nucleus and promotes the expression of genes involved in cell cycle, cell growth and de-differentiation together with its transcription factor binding partner, TEAD. Aberrant activity of YAP leads to hepatomegaly and oncogenic growth of hepatocytes. Our research activity is focused on the dissection of the mechanisms of the transcriptional regulation mediated by YAP in the liver.
As a model, we used transgenic mice in which an activated form of YAP is conditionally expressed in the liver. ChIP-Seq analyses reveals that YAP chromatin binding is dependent on TEAD and its activation leads to further chromatin binding, especially in distal regulatory elements. YAP induction is associated with the expression of genes involved in inflammation, cell cycle and liver cancer by promoting RNAPol2 pause release from their promoters. YAP also represses HNF4a target genes by reducing RNAPol2 elongation and chromatin accessibility on the promoters of these genes.
Bianchi, V., Ceol, A., Ogier, A., de Pretis, S., Galeota, E., Kishore, K., Bora, P., Croci, O., Campaner, S., Amati, B., Morelli, M.J., Pelizzola, M. Integrated Systems for NGS Data Management and Analysis: Open Issues and Available Solutions. Front. Genet. 2016 May 6.
Donato, E., Croci, O., Sabò, A., Muller, H., Morelli, M.J., Pelizzola, M., Campaner, S. Compensatory RNA Polymerase 2 loading determines the efficacy and transcriptional selectivity of JQ1 in Myc driven tumors. Leukemia. 2016 June 24.
Croci, O., De Fazio, S., Biagioni, F., Donato, E., Caganova, M., Curti, L., Doni, M., Sberna, S., Aldeghi, D., Biancotto, C., Verrecchia, A., Olivero, D., Amati, B., Campaner, S. Transcriptional integration of mitogenic and mechanical signals by Myc and YAP. Genes Dev. 2017 November 15.
Donato, E., Croci, O., Campaner, S. Elongation vs stalling: place your BET. Oncotarget. 2017 December 6.
Blaževitš, O., Bolshette, N., Vecchio, D., Guijarro, A., Croci, O., Campaner, S., Grimaldi, B. MYC-Associated Factor MAX is a Regulator of the Circadian Clock. Int J Mol Sci. 2020 March 26.
Wei, Q., Holle, A., Li, J., Posa, F., Biagioni, F., Croci, O., Benk, AS., Young, J., Noureddine, F., Deng, J., Zhang, M., Inman, GJ., Spatz, JP., Campaner, S., Cavalcanti-Adam, EA. BMP-2 Signaling and Mechanotransduction Synergize to Drive Osteogenic Differentiation via YAP/TAZ. Adv Sci (Weinh). 2020 June 16.