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Gerard Karsenty, M.D., Ph.D. - " The contribution of bone to whole organism physiology"

Department of Genetics and Development, Columbia University Medical Center, New York, USA
When May 14, 2018
from 12:00 PM to 01:30 PM
Where tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
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Abstract
I have devoted my entire scientific career to the biology of the skeleton. In the study of skeletal development, I along with others have identified Runx2 as the earliest and most specific determinant of osteoblast differentiation. I showed that it is mutated in a frequent human skeletal dysplasia called cleidocranial dysplasia. I identified functions of Runx2 during chondrogenesis, transcription factors interacting with Runx2 and ATF4 as another transcription factor enriched in osteoblasts and acting downstream of Runx2. I also identified Gcm2 as the earliest determinant of parathyroid gland development. In the study of skeletal physiology which is the main focus currently of the lab, I identified a gene inhibiting extracellular matrix mineralization and provided a genetic framework for why extracellular matrix mineralization occurs only in bone and teeth. Most of the current activity in the lab is focused on exploring the hypotheses I proposed 18 years ago that there is a coordinated regulation, endocrine in nature, of bone growth, energy metabolism and reproduction. Testing all aspects of this hypothesis has allowed the lab to reveal the existence of a central control of bone mass and to identify on molecular and genetic grounds how this regulation is achieved. More recently, we have identified the bone-derived hormone osteocalcin has a biologically important regulator of insulin secretion and glucose homeostasis, energy expenditure, testosterone secretion and male fertility. Osteocalcin regulatory functions go beyond the contours define by our original hypothesis and for instance osteocalcin crosses the blood brain barrier and its signaling in the brain is needed for brain development and cognitive functions in adult animals. Osteocalcin signaling in myoblasts is also needed for adaptation to exercise in part because it favors the production of interleukin 6 by muscle. We have identified two receptors for osteocalcin, one mediating its peripheral function and another one mediating its central functions. Currently we are defining a single con conceptual framework that will encompass all the known functions of osteocalcin and are using this framework to identify novel functions of this hormone and altogether to redefine what has been skeletal biology throughout evolution. 

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