Special Seminar - Assembling and Interrogating the Regulatory Logic of Cancer Cells to Elucidate Mechanisms of Non-oncogene Addictions
Date: April 26, 2012
Time: 2:00 PM
Location: Bossone Research Enterprise Center, Room: 709
Andrea Califano, PhD
Department of Biomedical Informatics
The recent onslaught of molecular data, across multiple human malignancies, is producing an unprecedented repertoire of genetic and epigenetic alterations contributing to tumorigenesis and progression. Yet, the direct impact of this knowledge on tumor treatment and prevention is still largely unproven. Loss of tumor suppressor function is difficult to target pharmacologically and, with a handful of exceptions, alterations providing potential drug targets are relatively infrequent in cancer patients and are thus unlikely to support clinical development.
By using these data to reconstruct and interrogate the regulatory logic of thecancer cell, which is responsible for integrating multiple aberrant signals in vivo, systems biology is starting to elucidate broad addiction mechanisms, both oncogene and non-oncogene based that are exquisitely specific to the cancer subtype. In this presentation, we will discuss recent result in the discovery of synergistic, non-oncogene addiction mechanisms in high-grade glioma, of the upstream genetic alterations causally related to their functional activation, and of candidate targets for combination therapy. This approach has been generalized to a number of additional tumor subtypes and provides a novel framework for cancer target discovery and development in patient centric fashion.
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.
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.
The Bossone Research Enterprise Center is located at the corner of 32nd and Market Streets.