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Department of Pathology

 
cell division
cytokinesis
cytoskeleton
kinases
phosphatases
chromosomal instability

Biography

I obtained my PhD in Molecular and Cellular Genetics at the University of Naples, Italy, working on hormonal regulation of gene expression in Drosophila. I continued my career as an HHMI Postdoctoral Research Associate at the Department of Human Genetics of the University of Utah, Salt Lake City, USA, from 1995 to 1998 to study hormonal-induced tissue remodelling during Drosophila metamorphosis. In 1999, after being awarded an EMBO fellowship, I moved to Cambridge, UK, to join the Department of Genetics where he continued to study cytoskeleton dynamics during cell division in both Drosophila and human cells. In 2004, I became Senior Research Associate and in 2007 established my own research group always at the Department of Genetics. I was appointed Lecturer at the Department of Pathology of the University of Cambridge in 2009 and promoted to Senior Lecturer in 2020.

Research

My research interests focus on the study of the mechanisms and signalling pathways that control the mechanics and regulation of cell division in normal and cancer cells. The major focus of the lab over the past 15 years has been to understand how kinases and counteracting phosphatases control cytoskeletal dynamics, protein function and interactions during cell division, with particular emphasis on cytokinesis. In recent years I have been interested in characterising mitotic protein-protein interaction networks using affinity purification coupled with mass spectrometry (AP-MS) and in understanding how the mitotic kinases Aurora B, Plk1 and CIT-K and their counteracting PP1 and PP2A phosphatases regulate the activity and interactions of cytokinesis proteins in human cells. Our studies have led to the identification of several novel interaction networks and to the characterisation of molecular mechanisms by which kinases and phosphatases regulate key processes during cytokinesis. 

Some of our major research achievements during the past 15 years are: 

  • Comprehensive proteomic survey of the Drosophila cell division interactome;
  • The identification of the role of the centralspindlin complex in promoting cleavage furrow ingression;
  • The finding that the cytoskeletal binding protein Anillin plays a key role in scaffolding and connecting the contractile ring with central spindle microtubules; 
  • The characterisation of a novel mechanism controlling the final separation of the two daughter cells at the end of cell division involving the regulation of ESCRT-III by the chromosomal passenger complex;
  • The discovery that Citron kinase is the key regulator of the assembly and organisation of an organelle, the midbody, which controls the separation of the two daughter cells and has also been implicated in determining cell fate, apical-basal polarity, and cilium and lumen formation;
  • The identification of a cross-regulatory mechanism between Aurora B and CIT-K that controls the localization and function of these two kinases during cytokinesis and the proper organisation of the midbody;
  • The characterisation of the human midbody proteome and interactome;
  • The discovery that the PP1-MYPT1 phosphatase regulates microtubule dynamics in late cytokinesis by antagonising Aurora B kinase.

 

  • Research Associates:
    Luisa Capalbo
  • Graduate Students:
    Ella Halcrow, Kethan Suvarna

Publications

Key publications: 

1) Bassi I.Z., Audusseau, M., Riparbelli, M.G., Callaini, G. and D’Avino P.P. (2013) Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proceedings of the National Academy of Sciences USA, 110(24):9782-9787.

2) D’Avino,P.P., Giansanti, M. and Petronczki, M. (2015) Cytokinesis in animal cells. Cold Spring Harbor Perspective in Biology, 13;7(4):a015834..

3) McKenzie C., Bassi I.Z., DebskiJ., Gottardo M., Callaini, G., DadlezM. and D’Avino P.P. (2016) Cross-regulation between Aurora B and Citron kinase controls midbody architecture in cytokinesis. Open Biology, 6: 160019 (doi: 10.1098/rsob.160019).

4) Capalbo, L., Mela, I., Abad, M.A., Jeyaprakash A.A., Edwardson, J.M.and D’Avino P.P. (2016) Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis.Open Biology, 6: 160248(doi: 10.1098/rsob.160248)

5) McKenzie, C. and D’Avino P.P. (2016)Investigating cytokinesis failure as a strategy in cancer therapy. Oncotarget, 7(52):87323-87341 (doi: 10.18632/oncotarget.13556)

6) D’Avino P.P. (2017). Citron kinase - renaissance of a neglected mitotic kinase. Journal of Cell Science130(10): 1701-1708; doi: 10.1242/jcs.200253.

7) Capalbo, L., Bassi, Z.,  Geymonat, M., Todesco, S., Copoiu, Enright, A.,  L., Callaini, G., Riparbelli, M.G.,Yu, L., Choudhary, J., Ferrero, E, Wheatley, S., Douglas, M.E.,  Mishima, M. and D’Avino P.P. (2019). The midbody interactome reveals new unexpected roles role for PP1 phosphatases in cytokinesis. Nature Communications, 10(1):4513.

8) Scott, S.J., K. Suvarna, and D’Avino P.P (2020). Synchronization of human retinal pigment ephitilial-1 (RPE-1) cells in mitosis. Journal of Cell Science, 133(18):jcs247940; doi: 10.1242/jcs.247940. 

9) Lim, Y., D. De Bellis, J.J. Sandow, L. Capalbo, D’Avino P.P., J.M. Murphy, A.I. Webb, L. Dorstyn, and S. Kumar (2021). Phosphorylation by Aurora B kinase regulates caspase-2 activity and function. Cell Death & Differentiation, 28(1):349-366. doi: 10.1038/s41418-020-00604-y.

10) Scott, S.J., X. Li, S. Jammula, G. Devonshire, C. Lindon, R.C. Fitzgerald, and D’Avino P.P (2021). Evidence that polyploidy in esophageal adenocarcinoma originates from mitotic slippage caused by defective chromosome attachments. Cell Death & Differentiation, doi: 10.1038/s41418-021-00745-8.

Associate Professor
Division of Cellular and Molecular Pathology
Dr Paolo  D'Avino

Contact Details

Department of Pathology
University of Cambridge
Tennis Court Road
Cambridge
CB2 1QP
+44 (0)1223 333712
Takes PhD students
Not available for consultancy

Affiliations

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