Califano Info

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Dr. Andrea Califano

Contact:
1130 St. Nicholas Avenue
New York, NY 10032
mailto:califano@c2b2.columbia.edu
Fax:(212) 851-4630

For a detailed biography click the following link File:Califano Bio Dec 2012.pdf

ARACNEMYC.JPG
  • Clyde and Helen Wu Professor of Chemical Systems Biology
in the Columbia Initiative in Systems Biology (CISB),
Department of Biochemistry and Molecular Biophysics,
Department of Biomedical Informatics,
Institute for Cancer Genetics,
  • Founding Director and Chair,
Columbia Initiative in Systems Biology which includes the Sulzberger Columbia Genome Center (CGC)
and the Center for Computational Biology and Bioinformatics (C2B2), which is currently undergoing formal approval to department status.
  • Director, Judy Sulzberger Columbia Genome Center (CGC)
  • Associate Director, Herbert Irving Comprehensive Cancer Center (HICCC)

Contents

Scientific Interests

Dr. Califano’s interests reside in the assembly and interrogation of gene regulatory models for the elucidation of mechanisms presiding over cell physiology and their dysregulation in disease, with specific applications to cancer, stem cells, and neurodegenerative disease. His lab, which integrates both experimental and computational research, has pioneered the first genome-wide regulatory model of human cells and a variety of methods for the identification of master regulators of aberrant transformation and physiological differentiation/maturation events and their controlling genetic alterations. These approaches have led to the discovery of several new genes in glioma, leukemia, lymphoma, and prostate cancer that can be targeted pharmacologically to abrogate tumorigenesis. He has also pioneered network-based methods for the elucidation of mechanisms of action of drugs, drug synergy, and drug sensitivity.

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.

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.

In 2008, he co-funded Therasis, Inc. a company dedicated to the development of combination therapy approaches

Dr. Califano serves on numerous editorial and scientific advisory boards, including the Board of Scientific Advisors of St. Jude Children’s Hospital, the Sanford-Burnham Institute, MD Anderson Genomic Medicine department, and 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:

  1. The reverse engineering and biochemical validation of gene regulatory and signaling networks in mammalian cellular contexts.
  2. The study of genetic regulatory modules that are disregulated in lymphoid malignancies and other human malignancies, using a systems biology approach.
  3. The dissection of regulatory networks necessary for pluripotency and lineage specific differentiation of human Stem Cells.
  4. The application of systems biology methods to the dissection of normal and pathologic phenotypes.
  5. The identification of cis-regulatory elements and modules in the non-coding genome of higher eukaryotes.

Selected Reviews and Commentaries

  1. Califano A, Butte AJ, Friend S, Ideker T, Schadt E. Leveraging models of cell regulation and GWAS data in integrative network-based association studies. Nat Genet. 2012 Jul 27;44(8):841-7
  2. Lefebvre C, Rieckhof G, Califano A. Reverse-engineering human regulatory networks. Wires Syst Biol Med. 2012;4(4):311-25.
  3. Floratos A, Honig B, Pe'er D, Califano A. Using systems and structure biology tools to dissect cellular phenotypes. J Am Med Inform Assn. 2012;19(2):171-5. PubMed PMID: ISI:000300768100006.
  4. Meyer P, Alexopoulos LG, Bonk T, Califano A, Cho CR, de la Fuente A, et al. Verification of systems biology research in the age of collaborative competition. Nat Biotechnol. 2011;29(9):811-5.
  5. Califano A. Rewiring makes the difference. Mol Syst Biol. 2011;6.
  6. Califano A. Striking a Balance Between Feasible and Realistic Biological Models. Sci Transl Med. 2011;3(103).

Selected Publications (Click here for a more comprehensive list)

  1. Wang ZA, Mitrofanova A, Bergren SK, Abate-Shen C, Cardiff RD, Califano A, Shen MM. Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity., Nat Cell Biol. 2013 PMID: 23434823
  2. Zhang QC, Petrey D, Deng L, Qiang L, Shi Y, Thu CA, Bisikirska B, Lefebvre C, Accili D, Hunter T, Maniatis T, Califano A, Honig B. Structure-based prediction of protein-protein interactions on a genome-wide scale, Nature 2012 Sep 30. PMID: 23023127
  3. Wang J, Kobayashi T, Floc'h N, Kinkade CW, Aytes A, Dankort D, Lefebvre C, Mitrofanova A, Cardiff RD, McMahon M, Califano A, Shen MM, Abate-Shen C. B-Raf Activation Cooperates with PTEN Loss to Drive c-Myc Expression in Advanced Prostate Cancer, Cancer Reserch 2012 Sep 15. PMID: 22836754
  4. Floch N, Kinkade CW, Kobayashi T, Aytes A, Lefebvre C, Mitrofanova A, Cardiff RD, Califano A, Shen MM, Abate-Shen C. Dual targeting of the Akt/mTOR signaling pathway inhibits castration-resistant prostate cancer in a genetically engineered mouse model. Cancer Res. 2012 Jul 19
  5. Martinez MR, Corradin A, Klein U, Alvarez MJ, Toffolo GM, di Camillo B, et al. Quantitative modeling of the terminal differentiation of B cells and mechanisms of lymphomagenesis. P Natl Acad Sci USA. 2012;109(7):2672-7.
  6. Della Gatta G, Palomero T, Perez-Garcia A, Ambesi-Impiombato A, Bansal M, Carpenter ZW, et al. Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL. Nat Med. 2012;18(3):436-U198
  7. Sumazin P, Yang XR, Chiu HS, Chung WJ, Iyer A, Llobet-Navas D, et al. An Extensive MicroRNA-Mediated Network of RNA-RNA Interactions Regulates Established Oncogenic Pathways in Glioblastoma. Cell. 2011;147(2):370-81.
  8. Kruithof-de Julio M, Alvarez MJ, Galli A, Chu JH, Price SM, Califano A, et al. Regulation of extra-embryonic endoderm stem cell differentiation by Nodal and Cripto signaling. Development. 2011;138(18):3885-95.
  9. De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan PD, Kelliher M, Kee BL, Pandolfi PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi S, Meijerink JP, Cordon-Cardo C, Califano A, Ferrando AA. The TLX1 oncogene drives aneuploidy in T cell transformation, Nat Med. 2010 Oct 24. PMID: 20972433
  10. Cancer Target Discovery and Development Network, Schreiber SL, Shamji AF, Clemons PA, Hon C, Koehler AN, Munoz B, Palmer M, Stern AM, Wagner BK, Powers S, Lowe SW, Guo X, Krasnitz A, Sawey ET, Sordella R, Stein L, Trotman LC, Califano A, Dalla-Favera R, Ferrando A, Iavarone A, Pasqualucci L, Silva J, Stockwell BR, Hahn WC, Chin L, DePinho RA, Boehm JS, Gopal S, Huang A, Root DE, Weir BA, Gerhard DS, Zenklusen JC, Roth MG, White MA, Minna JD, MacMillan JB, Posner BA. Towards patient-based cancer therapeutics, Nat Biotechnol. 2010 Sep;28(9):904-6. PMID: 20829823
  11. Lefebvre C, Rajbhandari P, Alvarez MJ, Bandaru P, Lim WK, Sato M, Wang K, Sumazin P, Kustagi M, Bisikirska BC, Basso K, Beltrao P, Krogan N, Gautier J, Dalla-Favera R, Califano A. A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers, Mol Syst Biol. 2010 Jun 8;6:377. PMID: 20531406
  12. Floratos A, Smith K, Ji Z, Watkinson J, Califano A. geWorkbench: an open source platform for integrative genomics, Bioinformatics 2010 Jul 15;26(14):1779-80. Epub 2010 May 28. PMID: 20511363
  13. Klein U, Lia M, Crespo M, Siegel R, Shen Q, Mo T, Ambesi-Impiombato A, Califano A, Migliazza A, Bhagat G, Dalla-Favera R. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia, Cancer Cell. 2010 Jan 19;17(1):28-40. PMID: 20060366
  14. Alvarez MJ, Sumazin P, Rajbhandari P, Califano A. Correlating measurements across samples improves accuracy of large-scale expression profile experiments, Genome Biol. 2009;10(12):R143. PMID: 20042104
  15. Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X, Snyder EY, Sulman EP, Anne SL, Doetsch F, Colman H, Lasorella A, Aldape K, Califano A, Iavarone A. The transcriptional network for mesenchymal transformation of brain tumours, Nature. 2010 Jan 21;463(7279):318-25. PMID: 20032975
  16. Basso K, Saito M, Sumazin P, Margolin AA, Wang K, Lim WK, Kitagawa Y, Schneider C, Alvarez MJ, Califano A, Dalla-Favera R. Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal center B cells. Blood. 2010 Feb 4;115(5):975-84.
  17. 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, Califano A. Genome-wide identification of post-translational modulators of transcription factor activity in human B cells. Nat Biotechnol. 2009 Sep;27(9):829-39.
  18. Zhao X, D' Arca D, Lim WK, Brahmachary M, Carro MS, Ludwig T, Cardo CC, Guillemot F, Aldape K, Califano A, Iavarone A, Lasorella A. The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain. Dev Cell. 2009 Aug;17(2):210-21.
  19. 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
  20. Basso K, Sumazin P, Morozov P, Schneider C, Maute RL, Kitagawa Y, Mandelbaum J, Haddad J Jr, Chen CZ, Califano A, Dalla-Favera R. Identification of the human mature B cell miRNome. Immunity. 2009 May;30(5):744-52.
  21. Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q, Bertoni F, Ponzoni M, Scandurra M, Califano A, Bhagat G, Chadburn A, Dalla-Favera R, Pasqualucci L. [http://www.ncbi.nlm.nih.gov/pubmed/19412164 Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature. 2009 Jun 4;459(7247):717-21.
  22. Lim WK, Lyashenko E, Califano A. Master regulators used as breast cancer metastasis classifier. Pac Symp Biocomput. 2009:504-15.
  23. Wang K, Alvarez MJ, Bisikirska BC, Linding R, Basso K, Dalla Favera R, Califano A. Dissecting the interface between signaling and transcriptional regulation in human B cells. Pac Symp Biocomput. 2009:264-75.
  24. Margolin AA*, Palomero T, Sumazin P, Califano A*, Ferrando A*, Stolovitzky G*, 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.
  25. Mani KM, Lefebvre C, Wang K, Lim WK, Basso K, Dalla-Favera R, Califano A. A systems biology approach to prediction of oncogenes and molecular perturbation targets in B-cell lymphomas. Mol Syst Biol. 2008;4:169
  26. Margolin AA, Wang K, Lim WK, Kustagi M, Nemenman I, Califano A. Reverse engineering cellular networks Nature Protocols. 2006. 1(2):662-671.
  27. Sosinsky A, Honig B, Mann RS, Califano A. 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.
  28. 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 NOTCH1 directly regulates MYC expression and controls oncogenic cell growth Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18261-6. Epub 2006 Nov 17. Erratum in: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4240.
  29. Margolin AA, Nemenman I, Basso K, Wiggins C, Stolovitzky G, Dalla Favera R, Califano A. ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics. 2006 Mar 20;7 Suppl 1:S7.
  30. Basso Katia, Margolin Adam A, Stolovitzky Gustavo, Klein Ulf, Dalla-Favera Riccardo, & Califano Andrea Reverse engineering of regulatory networks in human B cells Nature Genetics 2005 37, 382 - 390
  31. Katia Basso, Ulf Klein, Huifeng Niu, Gustavo A. Stolovitzky, Yuhai Tu, Andrea Califano, Giorgio Cattoretti, and Riccardo Dalla-FaveraTracking CD40 signaling during germinal center development Blood 2004 , 15 December 2004, Vol. 104, No. 13, pp. 4088-4096.
  32. Basso Katia, Liso Arcangelo, Tiacci Enrico, Benedetti Roberta, Pulsoni Alessandro, Foa Robin, Di Raimondo Francesco, Ambrosetti Achille, Califano Andrea, Klein Ulf, Dalla Favera Riccardo, and Falini Brunangelo Gene Expression Profiling of Hairy Cell Leukemia Reveals a Phenotype Related to Memory B Cells with Altered Expression of Chemokine and Adhesion Receptors J. Exp. Med. 2004, Volume 199, Number 1, 59-68
  33. Liu A, Zhang X., Stolovitzky G, Califano A, and Firestein S, Motif-Based Construction of a Functional Map for Mammalian Olfactory Receptors, Genomics. 2003 May;81(5):443-56.
  34. Klein Ulf, Tu Yuhai, Stolovitzky Gustavo A., Keller Jeffrey L., Haddad Jr. Joseph, Miljkovic Vladan, Cattoretti Giorgio, Califano Andrea, and Dalla-Favera Riccardo Transcriptional analysis of the B cell germinal center reaction Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2639-44.
  35. Küppers Ralf, Klein Ulf, Schwering Ines, Distler Verena, Bräuninger Andreas, Cattoretti Giorgio, Tu Yuhai, Stolovitzky Gustavo A., Califano Andrea, Hansmann Martin-Leo, and Dalla-Favera Riccardo Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling J Clin Invest. 2003 February 15; 111(4): 529–537.
  36. Buchanan A, Califano A, Kahn J, McPherson E, Robertson J, Brody B. Pharmacogenetics: ethical issues and policy options. Kennedy Inst Ethics J. 2002 Mar;12(1):1-15.
  37. Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 2002, Jan 24;415(6870):436-42.
  38. 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;19(11):1625-38.
  39. Califano A, Stolovitzky S and Tu Y, Analysis of Gene Expression Microarrays for Phenotype Classification, Proc Int Conf Intell Syst Mol Biol. 2000
  40. Califano A Splash, Structural Pattern Localization Analysis by Sequential Histograms Bioinformatics 2000. Apr;16(4):341-57.
  41. Califano A, Rigoutsos I. [FLASH: a fast look-up algorithm for string homology]. Proc Int Conf Intell Syst Mol Biol. 1993;1:56-64.
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