 Andrea Califano, Dr. Professor of Biomedical Informatics |
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Director, Columbia Initiative in Systems Biology
Director, Center for the Multiscale Analysis of Genetic Networks (MAGNet)
Associate Director for Bioinformatics, Irving Cancer Research Center (ICRC)
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Scientific Interests
Dr. Califano's interests are broadly defined within the field of Systems Biology, with specific application to human malignancies. In particular his lab has spearheaded early efforts to assemble genome-wide, context-specific maps of molecular interactions in human cells, by integrating several reverse engineering approaches. These maps have shown significant promise in the rational elucidation of both physiological and pathological phenotypes.
Over the last few years, his lab has assembled biochemically validated, genome-wide map of transcriptional and post-transcriptional interaction in several human cell contexts, including B cell, Breast Carcinoma, Glioma, and normal and tumor-related Stem Cells. These maps are being extensively used for the unbiased dissection of dysregulated pathways in related human malignancies. The Califano lab integrates the development of analytical methodologies with high-throughput experimental assays necessary for data generation and biochemical/biological validation.
Background
Dr. Califano's doctoral thesis in physics, at the University of Florence, was
on the behavior of high-dimensional dynamical systems . From 1986 to 1990, as a Research Staff Member in the Exploratory Computer Vision Group at the IBM TJ Watson Research Center he worked on several algorithms for machine learning, more specifically for the interpretation of 2D and 3D visual scenes.
In 1990 Dr. Califano started his activities in Computational Biology and, in 1997, became the program director of the IBM Computational Biology Center, a worldwide organization active in several research areas related to bioinformatics, chemoinformatics, complex biological system modeling/simulation, microarray analysis, protein structure prediction, and molecular-dynamics.
In 2000 he co-founded First Genetic Trust, Inc. to actively pursue translational genomics research and infrastructure related activities in the context of large-scale patient studies with a genetic components.
Finally, in 2003, he joined Columbia University as Professor of Biomedical Informatics, with appointments in the Department of Biomedical Informatics and in the Institute for Cancer Genetics.
Dr. Califano currently serves as a member of the Board of Scientific Advisors of the National Cancer Institute.
Research Topics
The Califano lab is interested in a variety of themes at the interface between the computational and the experimental biological sciences, including:
- The reverse engineering and biochemical validation of gene regulatory and signaling networks in mammalian cellular contexts.
- The study of genetic regulatory modules that are disregulated in lymphoid malignancies and other human malignancies, using a systems biology approach.
- The dissection of regulatory networks necessary for pluripotency and lineage specific differentiation of human Stem Cells.
- The application of systems biology methods to the dissection of normal and pathologic phenotypes.
- The identification of cis-regulatory elements and modules in the non-coding genome of higher eukaryotes.
Selected Publications
- Wang K, Saito M, Bisikirska BC, Alvarez MJ, Lim WK, Rajbhandari P, Shen Q, Nemenman I, Basso K, Margolin AA,Klein U, Dalla-Favera R, and Califano A, Genome-wide Identification of Post-translational Modulators of Transcription Factor Activity in Human B-Cells, Sept. 2009, Nat. Biotech, in press.
- Zhao X, D’ Arca1 D, Lim WK, Brahmachary M, Carro MS, Ludwig T, Guillemot F, Aldape K, Califano A, Iavarone A,and Lasorella A, The ubiquitin ligase Huwe1 regulates proliferation and neurogenesis by suppressing a N-Myc-DLL3 cascade in the developing brain, Developmental Cell, 2009, Aug. 18, 17(2):210-221.
- Saito M, Novak U, Piovan E, Basso K, Sumazin P, Schneider C, Crespo M, Shen Q, Bhagat G, Califano A, Chadburn A, Pasqualucci L, Dalla-Favera R., BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma, Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11294-9.
- Basso K, Sumazin P, Morozov P, Schneider C, Kitagawa Y, Maute RL, Mandelbaum J, Haddad J, Chen CZ, Califano A* and Dalla-Favera R (2009) Identification of the human mature B cells miRNome, Immunity, 2009 May;30(5):744-52.
- Compagno M, Lim WK, Grunn A, Nandula SV, Bertoni F, Ponzoni M, Scandurra M, Califano A, Bhagat G, Chadburn A, Dalla-Favera R, and Pasqualucci L (2009) Mutations at multiple genes cause deregulation of the NF-kB pathway in diffuse large B-cell lymphoma, Nature 2009 Jun 4;459(7247):717-21
- Lim WK, Lyashenko E, and Califano A (2009) Master Regulators Used As Breast Cancer Metastasis Classifier Pac Symp Biocomput. 2009:504-15.
- Wang K, Alvarez M, Bisikirska BC, Linding R, Basso K, Dalla Favera R, and Califano A (2009) Dissecting the Interface Between Signaling and Transcriptional Regulation in Human B Cells, Pac Symp Biocomput. 2009:264-75
- Strasser B, Alvarez MJ, Califano A, Cerdán PD., A complementary role for ELF3 and TFL1 in the regulation of flowering time by ambient temperature, Plant J. 2009 Feb 2
- Margolin AA, Palomero T, Sumazin P, Califano A*, Ferrando A*, Stolovitzky G*, (2008) ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes, Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):244-9.
- Cadeiras M, Bayern M, Burke E, Dedrick R, Gangadin A, Latif F, Shazad K, Sinha A, Tabak EG, Marboe CC, Califano A*, and Deng MC (2008) “Gene expression profiles of patients with antibody-mediated rejection after cardiac transplantation” J Heart Lung Transplant. 2008 Aug;27(8):932-4.
- Dinov, I., …, Califano A, et al. (2008), “ iTools: A Framework for Classification, Categorization and Integration of Computational Biology Resources”. PLoS One, 2008. 3(5): p. e2265
- Piccaluga PP, Califano A, ... et al. (2008) Gene expression analysis provides a potential rationale for revising the histological grading of follicular lymphomas. Haematologica, May 19 2008
- Mani K, Lefebvre C, Wang K, Lim WK, Basso K, Dalla-Favera R, and Califano A, (2008) A Systems Biology Approach to the Prediction of Causal Oncogenic Mechanisms and Drug Mechanism-of-Action Profiles in Cancer Phenotypes, Molecular Systems Biology 4:169
- Stolovitzky GA, Monroe D, Califano A (2007) “ Dialogue on Reverse Engineering Assessment and Methods: the DREAM of high throughput pathway inference." Ann N Y Acad Sci. 2007 Oct 9;
- Margolin AA, Califano A (2007), “ Theory and limitations of genetic network inference from microarray data." Ann N Y Acad Sci. 2007 Oct 9;
- Lefebvre C, Lim WK, Basso K, Dalla Favera R, and Califano A (2006), "A context-specific network of protein-DNA and protein-protein interactions reveals new regulatory motifs in human B cells." Lecture Notes in Computer Science, Vol. 4532 Springer Verlag, ISBN: 978-3-540-73059-0. Also, Proceedings of the 2006 RECOMB Satellite Workshop on Systems Biology, San Diego.
- Lim WK, Wang K, Lefebvre C, Califano A “ Comparative analysis of microarray normalization procedures: effects on reverse engineering gene networks." Bioinformatics. 2007; 23(13): i282-8.
- Li Z, Zheng T, Califano A, and Floratos A (2007), “Pattern-based mining strategy to detect multi-locus association and gene environment interaction.” BMC Proceedings, 2007 1 (Suppl 1):S16.
- Sosinsky A., Honig B*, Mann R.S.* and Califano A (2007), “ Discovering transcriptional regulatory regions in Drosophila by a nonalignment method for phylogenetic footprinting." Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6305-10. Epub 2007 Mar 29
- Piccaluga PP, Agostinelli C, Califano A, Rossi M, Basso K, Zupo S, Went P, Klein U, Zinzani PL, Baccarani M, Dalla Favera R, Pileri SA. (2007), “ Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets." J Clin Invest. 2007 Mar;117(3):823-34
- Banerjee N. and Califano A, (2006) Transcription Factor Centric Discovery of Regulatory Elements in Mammalian Genomes Using Alignment- Independent Conservation Maps, 4th RECOMB Comparative Genomics Satellite Workshop, Montreal (CA).
- Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, O’Neal J, Neuberg D, Margolin AA, Weng A, Aster JC, Sigaux F, Soulier J, Look AT, Young R, Califano A and Ferrando A, (2006) NOTCH1 directly regulates MYC expression and controls oncogenic cell growth, in press, Proc. Natl. Acad. Sci USA.
- Margolin AA, Nemenman I, Basso K, Wiggins C, Stolovitzky G, Dalla Favera R and Califano A, (2006) ARACNE: An Algorithm for the Reconstruction of Gene Regulatory Networks in a Mammalian Cellular Context, BMC Bioinformatics;7(Suppl.1):S7, also arXiv.org/abs/q-bio.MN/0410037.
- Margolin AA, Wang K, Lim WK, Kustagi M, Nemenman I, Califano A (2006). Reverse engineering cellular networks. Nature Protocols; 1(2): 662-671.
- Wang K, Banerjee N, Margolin AA, Nemenman I, Califano A, (2006) Genome-wide discovery of modulators of transcriptional interactions in human B lymphocytes, in Proceedings of the 10th Annual International Conference on Research in Computational Molecular Biology (RECOMB).
- Basso K, Margolin A, Stolovitzky G, Klein U, Dalla-Favera R, and Califano A, (2005) Reverse engineering of regulatory networks in human B cells, Nat Genet.;37(4):382-90.
- Klein U, Tu Y, Stolovitzky GA, Keller JL, Haddad Jr. H, Miljkovic V, Cattoretti G, Califano A, and Dalla-Favera R,"Transcriptional Analysis of the B Cell Germinal Center Reaction," Proceedings of the National Academy of Science, 2003.
- Liu A, Zhang X., Stolovitzky G, Califano A, and Firestein S, “Motif-Based Construction of a Functional Map for Mammalian Olfactory Receptors,” accepted paper, to appear in Genomics, 2003.
- Liu A and Califano A, “CASTOR: Clustering Algorithm for Sequence Taxonomical Organization and Relationship,” accepted paper, to appear in the Feb. 2003 issue of the Journal of Computational Biology.
- Klein U, Tu Y, Stolovitzky GA, Mattioli M, Cattoretti G, Husson H, Freedman A, Inghirami G, Cro L, Baldini L, Neri A, Califano A, Dalla-Favera R. “Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells.” J Exp Med. 2001 Dec 3;194(11):1625-38.. (* Both Dalla-Favera and Califano are senior authors)
- Califano A, Stolovitzky S and Tu Y, “Analysis of Gene Expression Microarrays for Phenotype Classification”, in Proceedings of the 8th Symposium on Intelligent Systems for Molecular Biology, San Diego, 2000.
- Hart R, Royyuru AK, Stolovitzky G, and Califano A, “Systematic and Automated Discovery of Protein Sequence Patterns,” in J Comput Biol. 2000;7(3-4):585-600. also in Proceedings of Fourth Annual International Conference on Computational Molecular Biology, Tokyo, 2000.
- Califano A, “Splash, Structural Pattern Localization Analysis by Sequential Histograms,” Bioinformatics. 2000 Apr;16(4):341-57.
- Califano A, Rigoutsos I: “FLASH: A Fast Look-up Algorithm for String Homology,” In Proc. of the 1st Int'l Conference on Intelligent Systems for Molecular Biology, pages 353--359, Bethesda, MD, July 1993.
- Califano A and Mohan R “Multidimensional indexing for recognizing visual shapes.” in. IEEE Transactions on Pattern Analysis and Machine Intelligence, 16(4):373--392, April 1994. Also in Proc. of 1991 IEEE Conf. on Comp. Vision and Pattern Recognition, Maui, June 1991