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Gerard Karsenty, M.D., Ph.D., the new chairman of genetics and development, is a trained endocrinologist who became a research scientist after obtaining two NIH research fellowships in the 1980s. His plans to return to his native Paris were put on hold because he became so enamored with research, “practiced at the highest levels,” that he stayed on in the United States from 1987 to 1997 at the University of Texas, M.D. Anderson Cancer Center in Houston,
Gerard Karsenty
Gerard Karsenty
working, as a postdoctoral fellow, on the molecular biology of collagen and as an independent investigator on the molecular biology of bone. In 1998, Dr. Karsenty moved to Baylor College of Medicine in Houston and the next year became a professor in its department of molecular and human genetics. Dr. Karsenty has made many fundamental contributions to understanding skeletal development and skeletal physiology. He is an editor of the Journal of Cell Biology, Developmental Cell, and Cell Metabolism. His two graduate students, 12 postdoctoral fellows and a technician from Baylor will comprise his new lab in the Hammer Health Sciences Center. Dr. Karsenty has moved to New York with his wife, Patricia Ducy, Ph.D., a long-time collaborator who has a faculty appointment in pathology. He has two teenage children, Antoine and Cecile.
    The Department of Genetics & Development was previously headed by Frank Costantini, Ph.D., professor of genetics and development, who was acting chairman from January 2001 to 2005.
    Dr. Karsenty, who joined P&S in February, recently spoke with InVivo.

Please describe your research.
I developed an interest in skeletal biology because as a physician I saw many patients with debilitating skeletal diseases. I soon realized that bone degenerative diseases are the most common illnesses of people in developed countries. Likewise, congenital abnormalities of the skeleton are the most common inherited conditions. I am interested in all aspects of skeletal biology: How does cell differentiation occur in the skeleton during development? What are the genetic and molecular bases of the known functions of the skeleton? What other, as yet undiscovered, functions may skeletons have? My lab attempts to answer these questions using clinical information to formulate hypotheses and mouse genetics to test them. We study transcription factors regulating differentiation of mesenchymal cells into osteoblasts [bone-forming cells] and we search for hormones or signaling molecules that mediate known osteoblast functions, such as bone mineralization or bone formation. This led us to show that bone formation is under the control of the hypothalamus. In addition, we are now developing a large research program with the goal of uncovering how the skeleton may regulate functions of other organs in the body.

What have been some of your most significant findings?
As far as skeletal development, my lab has identified two of the three known transcription factors regulating osteoblast differentiation – RUNX-2, and ATF-4. As for skeletal physiology, my lab has elucidated the genetic bases of bone mineralization and shown that bone physiology is regulated by the hypothalamus. Indeed, we showed that leptin, a hormone made in adipocytes, regulates bone mass via the hypothalamus using the sympathetic nervous system as a mediator. We believed that an endocrine connection between appetite and bone mass existed because osteoporosis, a bone loss disease, develops after menopause and obesity protects against osteoporosis. Our findings have implications for the treatment of osteoporosis because certain drugs that inhibit the sympathetic nervous system can increase bone mass. I am a consultant on a small pilot project in California testing these drugs, which have been available generically for 20 years.

What are your plans for the department?
I came to Columbia because I’d like to influence my academic environment beyond my own lab and research. During my several visits to Columbia I realized this was possible here. The department is very strong in developmental biology, DNA dynamics and recombination, and I believe those areas must continue to be strong for the department to flourish. I’m proposing adding to this spectrum of genetic research a genetic study of physiological functions in vertebrates, and as a result, of the pathophysiology of degenerative diseases. The existence of a strong department of physiology should facilitate this enterprise. Another major attraction of the medical center is its particular strength in energy metabolism and neuroscience, areas where my lab is taking skeletal biology.

What is your message to graduate students and postdoctoral fellows?
The current department is very strong and my goals of bringing new research areas to it should be very appealing to M.D./Ph.D. students and postdoctoral fellows more acquainted with vertebrate physiology. As a department of basic science, my first goal is to foster relationships with other basic science departments to strengthen graduate and postdoctoral education. A longer term goal is to establish bridges with the medical departments in those areas we have in common and to show that clinicians and basic scientists can collaborate. Although the trend by the government to support translational science is valuable, most important for young scientists is to do the best possible research.

What’s most exciting about genetics today?
Molecular genetics has become so sophisticated that it can now address questions that will have an immediate impact on understanding and treating diseases on a molecular level. Through their basic research, geneticists can influence medicine very rapidly and in ways they don’t even suspect. The Columbia Genome Center, for example, is actively involved in identifying drugs to treat diseases such as diabetes, hypertension and obesity, the most severe degenerative diseases people face today.

—Robin Eisner