Cancer Structural Biology
The Cancer Structural Biology group (CSB) works with a multidisciplinary approach to cancer biology, combining bioinformatics of -omics data, structural biochemistry, and experimental approaches
Our research
In our research, we start from the analysis of high-throughput cancer data from tumor samples or cellular models to define key targets and markers. We then study the selected biomolecules under the lens of structural biology to understand their mechanisms and how they are affected by cancer alterations. We also apply structural methods to understand drug-target interactions in the context of drug repurposing. We validate our predictions using cellular and in-vitro assays (such as co-immunoprecipitation, peptide arrays, NMR chemical-shift perturbations, etc.).
From the biological point of view, our current research focused on proteins of the core autophagy machinery, lysosomal pathways, and key players in mitochondrial cell-death and their regulators (kinases, transcription factors, ubiquitinating enzymes, etc.).
We have three main ongoing research lines in the group: i) the discovery of new and non-conventional Short Linear Motifs (SLiMs) belonging to the class of BH3 (apoptosis) and LIR (autophagy) motifs and how they are regulated by post-translational modifications or altered by mutations found in cancer samples; ii) how lipid composition of different organelles can modulate the structure and function of proteins of the core autophagy machinery; iii) the application of cationic amphiphilic drugs and disulfiram in the context of drug repurposing.
Furthermore, our group is also developing and maintaining software or pipelines for bioinformatics available at our GitHub repository. In particular, we develop methods to predict allosteric changes upon interactions or mutations using graph theory (e.g., PyInteraph) and pipelines to annotate or classify the functional impact of missense mutations (e.g., MutateX).
Find us at X (Papaleo Labs @ElePapaleo) or Instagram (cbl_dk)
Fas AB, Maiani E, Sora V, Kumar M, Mashkoor M, Lambrughi M, Tiberti M; Papaleo E: The conformational and mutational landscape of the ubiquitin-like marker for the autophagosome formation in cancer, Autophagy 2021; 17(10):2828-2841
Colaprico A, Olsen C, Bailey MH, Odom GJ, Terkelsen T, Silva TC, Olsen AV, Cantini L, Zinovyev A, Barillot E, Noushmehr H, Bertoli G, Castiglioni I, Cava C, Bontempi G, Chen XS, Papaleo E: Interpreting pathways to discover cancer driver genes. Nat Commun 2020;11(1):69
Terkelsen T, Krogh A, Papaleo E: CAncer bioMarker Prediction Pipeline (CAMPP) – A standardized framework for the analysis of quantitative biological data. PLoS Comput Biol 2020;16(3):e1007665
Kønig SM, Rissler V, Terklsen T, Lambrughi M, Papaleo E: Alterations of the interactome of Bcl-2 proteins in breast cancer at the transcriptional, mutational and structural level. PLoS Comput Biol 2019;15(12):e1007485
Lambrughi M, De Gioia L, Gervasio FL, Lindorff-Larsen K, Nussinov R, Urani C, Bruschi M, Papaleo E: DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions. Nucleic Acids Res 2016;44(19):9096-9109
Group leader: Elena Papaleo
Elena Papaleo is the head of CSB. She has a solid background in bioinformatics, structural biology and biochemistry.
She received her PhD in 2006 from the University of Milano-Bicocca and carried out post-doctoral research in different institutes and universities in Italy, Spain and Denmark.
Dr. Papaleo is also active as Academic Editor for main open access journals such as PloS Computational Biology, PloS ONE, PeerJ, Frontiers in Molecular Biosciences. She is ambassador for open-access initiatives in science.
She is currently member of different European Networks and Consortia, such as the PLUMED consortium, and the ELIXIR 3D-BioInfo and IDP communities.
Her research interests are mainly in the field of the molecular mechanisms related to cancer alterations in coding regions of genes, aberrant post-translational modifications and cancer-related intrinsically disordered proteins or networks of protein-protein interactions.
ORCID: 0000-0002-7376-5894
Key funding
The Cancer Structural Biology group is among others funded by:
Novo Nordisk Foundation
Hartmann Foundation
Carlsberg Distinguished Fellowship
The PRACE initiative