Patricia F. Ducy, PhD

Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Pathology & Cell Biology at CUMC

Credentials & Experience

Education & Training

  • PhD, Molecular BIology & Genetics, Claude Bernard University (Lyon)

Research

Our research aims at defining the signaling network existing between the skeleton and other organs in the body using a combination of molecular and cell biology, mouse genetics, and physiological assays. Our main areas of interest include the crosstalk between pancreatic beta-cell biology and bone homeostasis, and the regulation of bone homeostasis by centrally controlled signals.

Bone is an expensive organ in terms of energy. A massive amount of proteins needs to be synthesized daily during bone growth, and during adulthood bones are constantly remodeled through a succession of destruction and formation that requires a remarkable supply of energy to bone cells. This demand is only magnified by the fact that the skeleton is one of the largest organs in the body. While a bony skeleton confers to vertebrate several survival advantages that justify this metabolic expense it also suggests that energy and bone metabolisms may regulate each other. Following this hypothesis we have identified osteocalcin as a bone-derived hormone regulating glucose metabolism and beta cell endowment. We have also have identified Gprc6a as the osteocalcin receptor in beta-cells and showed that osteocalcin/Gprc6a signaling regulates perinatal beta-cell proliferation. We are now testing whether a feed-forward loop between insulin production and osteocalcin secretion coordinates skeletogenesis and pancreas morphogenesis during development. We are also evaluating the role of osteocalcin during the beta-cells adaptation to pregnancy and are testing whether these cells declined proliferation and function during aging could be caused by decreased osteocalcin/Gprc6a signaling.

A second line of research in the lab is to evaluate the influence of brain-controlled signals on bone development, remodeling and osteocalcin secretion. Earlier studies have shown that brain serotonin negatively regulates the sympathetic tone, whose action on bone-forming osteoblasts via b2 adrenergic receptor signaling is deleterious for bone mass accrual. We used this observation to demonstrate that the deleterious effect of serotonin reuptake inhibitors (SSRIs) on bone health is caused by their stimulation of sympathetic output and could therefore by prevented by a co-treatment with a beta-blocker. We are now evaluating whether another brain-controlled molecule, melatonin, acts as a positive regulator of bone mass accrual by counteracting the negative effect of the sympathetic tone.

Research Interests

  • Endocrine crosstalks between the skeleton, the brain and the pancreas

Grants

THE DIALOGUE BETWEEN BONE AND THE BRAIN: ENDOCRINE AND MOLECULAR BASES (Federal Gov)

Jun 1 2015 - Apr 30 2021

CROSS-TALK BETWEEN SKELETON AND PANCREAS MORPHOGENESES DURING DEVELOPMENT (Federal Gov)

Apr 1 2015 - Mar 31 2018

OSTEOCALCIN: THE HORMONAL LINK BETWEEN BONE AND REPRODUCTION (Federal Gov)

Jul 1 2010 - Jun 30 2015

LRP5-DEPENDENT REGULATION OF BONE MASS ACCRUAL BY GUT-DERIVED SEROTONIN (Federal Gov)

Jul 1 2009 - May 31 2014

OSTEOCALCIN AS A REGULATOR OF ENERGY METABOLISM (Federal Gov)

Apr 1 1998 - Apr 30 2013

REGULATION OF BETA CELL PROLIFERATION BY OSTEOCALCIN (Private)

Sep 1 2008 - Aug 31 2011

Selected Publications

  • Ortuno MJ, Robinson ST, Subramanyam P, Paone R, Huang YY, Guo XE, Colecraft HM, Mann JJ, Ducy P. Serotonin-reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect. Nat Med. 22:1170-79 (2016).
  • Wei J, Hanna T, Suda N, Karsenty G, .
  • Inose H, Zhou B, Yadav VK, Guo XE, Karsenty G, Ducy P. Efficacy of serotonin inhibition in mouse models of bone loss. J Bone Miner. Res. 26:2002-11 (2011).
  • Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat. Med. 16:308-312 (2010).
  • Yadav VK, Arantes HP, Barros ER, Lazaretti M, Ducy P. Genetic Analysis of Lrp5 Function in Osteoblast Progenitors. Calcif. Tissue Int. 86: 382-388 (2010).
  • Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates -cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc. Natl. Acad. Sci. USA. 105:5266-70 (2008).
  • Yadav VK, Ryu J-H, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum: an entero-bone endocrine axis. Cell 135:825-37 (2008).