[K08] Determining the Role of Brain-Derived CCN3 in Bone and Marrow Fat Metabolism
Ente: National Institute of Diabetes and Digestive and Kidney Diseases
Scadenza: 2029-03-31
Importo max: 169.992 EUR
Paese: US
Descrizione
ABSTRACT/PROJECT SUMMARY
This application presents a five-year mentored research and training plan that will prepare Dr. Muriel Babey to
be a leader in the field of the skeletal, aging, and metabolic physiology. Dr. Babey completed her MD at the
University of Berne, Switzerland and her clinical fellowship of Endocrinology, Metabolism and Diabetes at the
University of California, San Francisco (UCSF). She is an Assistant Adjunct Professor in Endocrinology and
Diabetes at UCSF and supported by an NIDDK supplement for emerging physician-scientist under the
mentorship of Dr. Holly Ingraham. Dr. Babey’s long-term career goal is to unravel the fundamental mechanisms
governing the intricate interplay between skeletal, aging, and metabolic physiology. This project will facilitate
foundational discoveries for her independent research program, as she seeks to delineate the role of brain-
derived cellular communication network factor 3 (CCN3) in bone and marrow fat metabolism.
Based on multiple assays, CCN3 emerged as the most promising pro-osteogenic factor from KISS1 neurons of
the arcuate nucleus (ARCKISS1). The proposal builds on this recent discovery (11) and will further test the
hypothesis that CCN3 drives bone formation and reduces bone marrow fat. Using in vitro and in vivo models,
she proposes to 1) determine how the dose and levels of circulating brain-derived CCN3 affect bone formation
in vitro and in vivo assays and 2) determine the role of circulating CCN3 on bone and marrow fat metabolism
during aging, menopause and after a HFD dietary challenge. This work will provide strong evidence for further
development and future clinical trials of CCN3, ultimately providing a novel therapeutic approach for mitigating
osteoporosis and fracture risk.
The proposed career development plan includes training in brain stereotaxic surgery, skeletal stem cell biology
and osteocyte mediated perilacunar remodeling. Dr. Babey will learn all the skills needed for an independent
research career, including supervising trainees and staff, grant writing and scientific communication. She has
assembled a world-class mentorship team with complementary expertise in brain-body communication in female
physiology (Primary mentor, Dr. Holly Ingraham), skeletal stem cell biology (Co-Mentor, Dr. Thomas Ambrosi),
osteocyte mediated perilacunar remodeling and mechanobiology (Co-Mentor, Dr. Tamara Alliston), novel
therapeutic approach for human skeletal disorders and bone injuries (Advisor, Dr. Edward Hsiao), link basic
mechanism of metabolic regulation to causality in clinical patients (Advisor, Dr. Suneil Koliwad) and bone marrow
adipose tissue and bone crosstalk with nerves (Advisor, Dr. Erica Scheller). Dr. Babey, her mentors, and the
Department of Medicine at UCSF are fully committed to this proposal and to her goal of becoming an independent
physician-scientist by the completion of this training period.
Istituzione: STANFORD UNIVERSITY
PI: Muriel Babey
Progetto: 7K08DK133674-04
Settori: National Institute of Diabetes and Digestive and Kidney Diseases
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