Fanxin Long, Ph.D.

faculty photo
Professor of Orthopaedic Surgery
Department: Orthopaedic Surgery
Graduate Group Affiliations

Contact information
The Children's Hospital of Philadelphia, Abramson Research Center 902A
3615 Civic Center Blvd
Philadelphia, PA 19104
B.S. (Cell Biology)
Peking University, 1988.
M.A. (Biochemistry and Molecular Biology)
University of California, Santa Barbara, 1992.
Ph.D. (Developmental Biology)
Tufts University School of Medicine, 1997.
Permanent link
> Perelman School of Medicine   > Faculty   > Details

Description of Research Expertise

Research Interests
The Long lab seeks to understand the fundamental mechanisms underlying both normal skeletal development and the pathophysiology of bone disorders.

Key Words
mesenchymal stem/progenitor cells, metabolic and epigenetic regulation, skeletal cell differentiation and function, diabetic osteopenia, skeletal aging, bone development and regeneration

Research Details
Skeletal diseases, ranging from congenital dysplasia to osteosarcoma to osteoarthritis and osteoporosis, take a significant toll on human health. The overarching goal of our research is to discover key steps in the molecular or metabolic regulation of skeletal cell differentiation or function, with the hope of uncovering therapeutic targets for treating the various skeletal diseases. Many of our studies have centered around the role and mechanism of key developmental signals such as Hh, Wnt, Notch and Bmp in regulating skeletal development and homeostasis. Through mouse genetic studies, we have defined specific functions of the developmental signals in bone and cartilage cell differentiation. Our molecular and biochemical studies have led to the discovery that the developmental signals alter cell fate and activity in part through reprograming of the cellular metabolism of major energy substrates. Recently, the lab has identified cell-intrinsic disruption of glucose metabolism as a pathogenic basis for osteoarthritis and diabetic osteopenia. In other projects, we combine single-cell sequencing technology with genetic lineage-tracing or functional studies to identify skeletal stem/progenitor cells in the mouse, and to examine their contribution to bone maintenance or pathology.

Rotation Projects
Metabolic and epigenetic reprogramming during cell differentiation
Functional dissection of metabolic pathways in the skeleton of genetically modified mice
Lineage tracing of skeletal stem/progenitor cells in vivo
Other projects open for discussion

Selected Publications

Ji X, Seeley R, Li K, Song F, Liao X, Song C, Angelozzi M, Valeri A, Marmo T, Lee WC, Shi Y, Long F: Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes. Cell Chem Biol. July 2023.

Song F, Lee WD, Marmo T, Ji X, Song C, Liao X, Seeley R, Yao L, Liu H, Long F: Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic male mice. Elife May 2023.

Li K, Ji X, Seeley R, Lee WC, Shi Y, Song F, Liao X, Song C, Huang X, Rux D, Cao J, Luo X, Anderson SM, Huang W, Long F: Impaired glucose metabolism underlies articular cartilage degeneration in osteoarthritis. FASEB J. June 2022.

Lee WC, Ji X, Nissim I, Long F.: Malic Enzyme Couples Mitochondria with Aerobic Glycolysis in Osteoblasts. Cell Rep 32: 108108, Sep 2020.

Seung-Yon Lee and Fanxin Long: Notch signaling suppresses glucose metabolism in mesenchymal progenitors to restrict osteoblast differentiation. JCI 128(12): 5573, Dec. 2018.

Lee SY, Abel ED, Long F: Glucose metabolism induced by Bmp signaling is essential for murine skeletal development. Nat Commun. 9(1): 4831, Nov. 2018.

Yu Shi, Guangxu He, Wen-Chih Lee, Jenny A. McKenzie, Matthew J. Silva, Fanxin Long: Gli1 identifies osteogenic progenitors for bone formation and fracture repair. Nat Commun. 8(1): 2043, Dec 2017.

Shi Y, Chen J, Karner CM and Long F. : Hedgehog signaling activates a positive feedback mechanism involving insulin-like growth factors to induce osteoblast differentiation. PNAS 112(15): 4678-4683, March 2015.

Chen J. and Long F.: mTORC1 signaling critically controls mammalian skeletal growth through stimulation of protein synthesis. Development 141(14): 2848-2854, July 2014.

Emel Esen, Jianquan Chen, Courtney M. Karner, Adewole L. Okunade, Bruce W. Patterson, Fanxin Long. : WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation. Cell Metab. 17(5): 745-755, May 2013.

back to top
Last updated: 09/01/2023
The Trustees of the University of Pennsylvania