Angela M. Christiano, Ph.D.

Columbia is deeply committed to establishing the kind of institutional framework that will allow genetic discovery, analysis and manipulation, and clinical genetics to thrive in every department and every program. That goal requires a far-reaching vision and tools to make the vision reality.
     Helping to provide that vision is a new Center for Human Genetics, led by Angela M. Christiano, Ph.D. The center will unite more than 40 clinicians and researchers in the hunt to identify genes involved in complex inherited diseases such as asthma, Parkinson’s, and heart failure. It will integrate the work of excellent centers and programs like the Columbia Genome Center, the Institute for Cancer Genetics, the Center for Computational Biology and Bioinformatics, and the Gertrude H. Sergievsky Center. The new center will provide coordination and focus for six key areas of genetics: basic research, clinical research, genetic epidemiology and statistical and population genetics, genomics and proteomics, clinical genetics, and genetic education.
     Another important step toward a more integrated, 21st century genetics program was taken this year with the appointment of Gerard Karsenty, M.D., Ph.D., as chairman of the Department of Genetics and Development.
     An endocrinologist and a geneticist who combines mouse and human genetics in his work, Dr. Karsenty is particularly interested in how the skeleton develops and how its functions are orchestrated at the genetic level. His seminal research has shown that the same hormones regulate bone metabolism and energy metabolism, proving that bone mass is regulated in part by the brain. In his current research, he is working to show that the skeleton is an endocrine organ that regulates the function of various other organs and can play a key role in the onset of degenerative diseases, such as the metabolic syndrome.

Gerard Karsenty, M.D., Ph.D.

     As chairman of the department, Dr. Karsenty will foster relationships with other basic science departments to strengthen graduate and postdoctoral education and forge bridges with clinical departments to foster collaborations among clinicians and basic scientists.
     The NIH has placed genomics and proteomics at the forefront of its research priorities. The first of three major themes in the NIH’s “New Pathways to Discovery” explains the situation this way: “Future progress in medicine will require a quantitative understanding of the many interconnected networks of molecules that comprise our cells and tissues, their interactions, and their regulation. We need to more precisely know the combination of molecular events that lead to disease if we hope to truly revolutionize medicine.”
     With its world-class faculty and expertise in a wide range of scientific disciplines, Columbia has become a leader in this scientific revolution, receiving nearly $50 million of the $235 million in grants awarded by the NIH for its priority Roadmap projects in 2005. These grants have established three major research centers and collaborations: the Molecular Libraries Screening Center, the National Center for Multi-Scale Analysis of Genetic and Cellular Networks (MAGNet), and the New York Consortium on Membrane Protein Structure, part of the NIH Protein Structure Initiative.

James Rothman, Ph.D.

Molecular Libraries Screening Center: Most of the organic chemical compounds, known as small molecules, that are now used in biomedical research and as targets for treatment were initially discovered serendipitously rather than by design. Columbia is one of nine institutions selected by the NIH to establish a collaborative research network to screen for promising small molecules in an efficient, high-throughput approach that will speed scientific progress. Headed by James Rothman, Ph.D., director of the Judith P. Sulzberger, M.D., Columbia Genome Center and the Clyde and Helen Wu Professor of Chemical Biology in the Department of Physiology and Cellular Biophysics, the center uses large-scale methods to identify these small molecules, which will improve our study of genes, cells, and biochemical pathways in health and disease, with the ultimate goal of discovering new drug targets and treatments. The MLSC has already established a collection of 100,000 chemically diverse small molecules, some of which have known biological activities and others that have the potential to modulate novel biological functions. The collection will grow over time, and all of its data will be made available to both public and private-sector researchers.

Andrea Califano, Ph.D.

National Center for Multi-Scale Analysis of Genetic and Cellular Networks (MAGNet): The vast array of data generated by genomic and proteomic research demands innovative methods of organizing, sorting, and studying this information. “With approximately 20,000 genes in the human genome, there are trillions of possible interactions among genes and proteins within a cell. Exploring each one in the laboratory would take a very long time, even with current high-throughput methods,” says Andrea Califano, Ph.D., professor of biomedical informatics. That’s where computational biology and biomedical informatics come in. Columbia’s new MAGNet Center, one of a network of seven centers established by the NIH, will create computational methods and tools to help solve one of the biggest challenges in biology: understanding how all the genes and proteins inside cells work together to implement specific biological processes. “We plan to use computers and new methods of systems biology to predict which proteins are interacting with each other and with DNA, and how these interactions change in disease,” says Dr. Califano, who directs the new center. MAGNet is housed in Columbia’s Center for Computational Biology and Bioinformatics – C2B2 – to take advantage of the resources of this interdepartmental consortium.

Wayne Hendrickson, Ph.D.

New York Consortium on Membrane Protein Structure: The NIH’s Protein Structure Initiative, a national effort aimed at determining the three-dimensional shapes of many proteins and their role in health and disease, starts where the Human Genome Project left off. “Genes are important only in that they produce proteins, which are the tiny three-dimensional machines of life,” says Lawrence Shapiro, Ph.D., associate professor of ophthalmology and biochemistry and molecular biophysics and a principal investigator in the New York Consortium on Membrane Protein Structure, one of several newly named centers in the Protein Structure Initiative. Led by Columbia’s Wayne Hendrickson, Ph.D., University Professor, this specialized center will focus on developing novel methods for quickly determining the structures of proteins that attach to a cell’s outer envelope, or membrane – proteins that have traditionally been difficult to study. “Drug discovery has been lagging in recent years, and many of us believe that the development of drugs based on a protein’s structure is a much more efficient way to find the drugs we’d like to have,” says Dr. Hendrickson. Columbia researchers will also play major roles in two other centers: the New York Structural Genomics Research Consortium, led by Barry Honig, Ph.D., professor of biochemistry and molecular biophysics, which will focus on the structures of phosphatases (a type of protein particularly important in disease), and the Rutgers-led Northeast Structural Genomics Consortium.

Barry Honig, Ph.D.

     An important resource in Columbia’s genomic and proteomics research is the Center for Computational Biology and Bioinformatics – C2B2. The goal of the interdepartmental center is to catalyze research at the interface between biology and the computational and physical sciences. C2B2, co-directed by Drs. Barry Honig and Andrea Califano, supports active research programs in computational biophysics and structural biology, the modeling of regulatory, signaling, and metabolic networks, pattern recognition, machine learning, and functional genomics. Faculty from the Morningside and medical center campuses represent biochemistry and molecular biophysics, biomedical informatics, biological sciences, chemistry, computer science, applied physics and applied mathematics, electrical engineering, and computational learning systems.

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