Roberto Giambruno

Post Doc
Postdoctoral Researcher

Research Lines

Genomic Science

Center

CGS@SEMM Milano

About

I started my scientific career at the University of Palermo where I obtained in 2005 the Bachelor degree in Biological Sciences. Afterwards, I moved to the University “La Sapienza” of Rome where I completed my Master degree in Genetic and Molecular Biology. Then, I decided to continue my education by becoming a PhD student in the laboratory of Giulio Superti-Furga at the Center of Molecular Medicine (CeMM) of the Austrian Academy of Science in Vienna where I was enrolled in the Molecular Signal Transduction programme of the Medical University of Vienna. I completed my studies in 2014 by obtaining the PhD title and subsequently moved back to Italy to start my first postdoctoral research period in the laboratory of Davide Gabellini at the San Raffaele Scientific Institute. In particular, I was enrolled in the San Raffaele International Postdoctoral Programme – Marie Curie Actions. Lately, I won a postdoctoral position offered by the European Insititute of Oncology - IEO within the PhDiTalents programme. Starting from April 2020, I joined the lab of F. Nicassio at the Center for Genomic Science of IIT@SEMM. My main reaserch interests are protein-RNA and protein-protein interactions and interaction proteomics. Currently, I am focusing on the role of protein-RNA interactions in the targeted-dependent mediated degradation (TDMD) of microRNAs. 

 

Projects

ROBERTO GIAMBRUNO - Biochemical characterization of Target-directed miRNA degradation complex in Cancer cells

 

LAY SUMMARY

MicroRNAs (miRNAs) are small RNA molecules (18-25 nucleotides) that post-transcriptionally regulate gene expression. The levels of miRNAs are directly linked to the expression of their target genes and cells tightly regulate miRNA levels at several levels to fine-tune gene expression. Recently, our laboratory contributed to unveil a molecular mechanism named Target-Directed miRNA degradation (TDMD), which controls cellular miRNA levels by promoting miRNA degradation.

IMPACT

The expression of miRNAs has been found de-regulated in cancer cells and altered miRNA levels contribute to cancer progression as well as tumor cell resistance to chemotherapy. The identification and characterization of the molecular machineries that regulate miRNA levels can shed light on key biological molecules that can be pharmacologically targeted for cancer therapy.

PROJECT DESCRIPTION

Cellular RNAs have been found to degrade miRNAs through TDMD, as also reported by our group that showed that endogenous Serpine1 3’ UTR regulates the levels of miR-30c and miR-30b through TDMD (Ghini et al, 2018). TDMD requires the activity of different enzymes, most likely acting as a whole protein complex. In order to characterize all the proteins composing the putative TDMD complex, we will conduct an RNA affinity purification approach, named RNA-protein interaction detection (RaPID) (Ramanathan, 2018). This system allows the purification of the proteins associated with an RNA sequence of interest and their subsequent identification trough MS-based proteomics. RaPID will be conducted in our well-established model for studying the TDMD process. In particular, we will identify the proteins associated to Serpine1 3’ UTR during TDMD and select only those that are specifically enriched compared to a Serpine1 3’ UTR mutated form, which cannot trigger TDMD. These proteins will then be functionally validated to assess their contribution to TDMD in cancer cells, which have been found to manipulate the TDMD process to gain proliferative advantages.

Overall, our results will allow the biochemical characterization of the TDMD complex and assess the functional role of its subunits.

This project is supported by the AIRC Investigator Grant to Dr. Nicassio

 

Image RaPID

Selected Publications

 My most relevant publications are:

1) PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis.

Spadotto V.*, Giambruno R.*, Massignani E., Mihailovich M., Maniaci M., Patuzzo F., Ghini F., Nicassio F. and Bonaldi T.  (*equal contribution)

Nucleic Acids Res. 2020 Jan 10;48(1):96-115. doi: 10.1093/nar/gkz1051

 2) PRMT1 is recruited via DNA-PK to chromatin where it sustains the Senescence-Associated Secretory Phenotype in response to cisplatin.

Musiani D.*, Giambruno R.*, Massignani E., Ippolito M.R., Maniaci M., Jammula S., Manganaro D., Nicosia L., Pasini D. and Bonaldi T. (*equal contribution)                                            

Cell Reports 2020 Jan 28;30 (4):1208-1222.e9. doi: 10.1016/j.celrep.2019.12.061

3) Mass Spectrometry-Based Proteomics to Unveil the Non-coding RNA World.

Giambruno R.*, Mihailovich M.*, Bonaldi T. (*equal contribution)

Front Mol Biosci. 2018 Nov 8;5:90. doi: 10.3389/fmolb.2018.00090. eCollection 2018.

4) Identifying Kinase Substrates via a Heavy ATP Kinase Assay and Quantitative Mass Spectrometry

Müller A.*, Giambruno R*., Májek P., Hofer A., Bigenzahn J. W., Superti-Furga G., Jessen H. J., Bennett K. L. (*equal contribution)

Sci Rep. 2016 Jun 27;6:28107. doi: 10.1038/srep28107.

5) Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia.

Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D, Barsyte-Lovejoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senisterra G, Stukalov A, Huber KV, Schönegger A, Marcellus R, Bilban M, Bock C, Brown PJ, Zuber J, Bennett KL, Al-Awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G..

Nat Chem Biol. 2015 Aug;11(8):571-8. doi: 10.1038/nchembio.1859.

6) JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.

Boztug K, Järvinen PM, Salzer E, Racek T, Mönch S, Garncarz W, Gertz EM, Schäffer AA, Antonopoulos A, Haslam SM, Schieck L, Puchałka J, Diestelhorst J, Appaswamy G, Lescoeur B, Giambruno R, Bigenzahn JW, Elling U, Pfeifer D, Conde CD, Albert MH, Welte K, Brandes G, Sherkat R, van der Werff Ten Bosch J, Rezaei N, Etzioni A, Bellanné-Chantelot C, Superti-Furga G, Penninger JM, Bennett KL, von Blume J, Dell A, Donadieu J, Klein C.

Nat Genet. 2014 Sep;46 doi: 10.1038/ng.3069.

7) Affinity Purification Strategies for Proteomic Analysis of Transcription Factor Complexes.

Giambruno R*, Grebien F*, Stukalov A, Knoll C, Planyavsky M, Rudashevskaya EL, Colinge J, Superti-Furga G, Bennett KL. (*equal contribution)

J. Proteome Res. 2013 Aug 22. doi: 10.1021/pr4003323