Baohong Zhao, PhD

We study osteoimmunology, an interdisciplinary field linking bone biology and immune system, with a focus on the inflammatory regulation of gene expression and signaling in osteoclastogenesis, adipogenesis, skeletal damage and repair involved in diseases, such as osteoporosis and inflammatory arthritis. We utilize genetic approaches (knockout and transgenic mice), a combination of molecular and cellular methods, various next-generation sequencing techniques, multi-omics approaches, and disease models, such as osteoporosis, inflammatory arthritis and high fat diet-induced obesity/type 2 diabetes mouse models. We have worked extensively on signal transduction and crosstalk, genetic and epigenetic regulation of gene expression, cell differentiation and in vivo bone remodeling and metabolism. We have published work at Nature Medicine, Journal of Experimental Medicine, Journal of Clinical Investigation, Journal of Immunology, eLife, and Nature Communications.

Bone destruction is a severe consequence of many skeletal diseases, including the common but refractory diseases, inflammatory arthritis and osteoporosis, and is a major cause of morbidity and disability in rheumatoid arthritis (RA) patients. Our long term goals are to identify and understand the mechanisms that regulate bone remodeling in inflammatory settings, and to develop new therapeutic approaches to suppress pathological bone resorption, recover bone formation and repair skeletal damage based on our discoveries of pathogenic mechanisms and drug targets.

Research

Identification of distinct molecular mechanisms between inflammatory and physiological osteoclastogenesis

1. Intrinsic inhibitory mechanisms of osteoclast differentiation by TNF
2. Reprogramming of macrophage response to TNF by TGFβ signaling

Regulation of inflammatory bone remodeling by:

1. signaling pathways (TNF, IFN, Notch/RBP-J, Def6)
2. genome-wide epigenetic and transcriptional regulation of gene expression and function
3. noncoding RNAs (miRNAs and long non-coding RNAs)

Cross talk between bone and bone marrow adipose, and differential regulation of peripheral and bone marrow adiposity

Discovery of new bone marrow hematopoietic and non-hematopoietic progenitor populations in regulation of skeleton

Extramural Grant Funding

NIH/NIAMS
The Tow Foundation

Departments

Special Expertise

Osteoclast biology
Inflammatory regulation of bone metabolism
Transcriptomics analysis
Genetic and epigenetic regulation of gene expression and function
Signal transduction and crosstalk between TNF, TGFbeta, Notch/RBP-J, IFN, ITAM and RANKL signaling pathways
Discovery of previously unrecognized bone marrow progenitors

Appointments

Affiliations

Department of Medicine, Weill Medical College of Cornell University
Graduate Program in Cell & Developmental Biology, Weill Medical College of Cornell University

Education

PhD, Showa University, Japan
DMD, Peking University, China
BM, Peking University, China

Awards

NIH/NIAMS Pathway to Independence Award (2012)
Osteoimmunology Young Investigator Award (Greece 2012)
Harold M. Frost Young Investigator Award (2011)
John Haddad Young Investigator Award (AIMM 2010)
ASBMR Young Investigator Award (2007)

Languages

English, Chinese, Japanese

Selected Journal Articles

Xia Y, Inoue K, Du Y, Baker S, E. Reddy EP, Greenblatt M, Zhao B. TGFβ reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis, Nature Communications 13, 3920 (2022). https://doi.org/10.1038/s41467-022-31475-1 *Highlighted by 2021 ASBMR annual meeting; *ASBMR Webster Jee Award.

Deng Z, Ng C, Inoue K, Chen Z, Xia Y, Hu X, Greenblatt M, Pernis A and Zhao B. Def6 regulates endogenous type I interferon responses in osteoblasts and suppresses osteogenesis. eLife, 2020; 9: e59659. PMID: 33373293 PMC7771961

Inoue K, Hu X, Zhao B. Regulatory network mediated by RBP-J/NFATc1-miR182 controls inflammatory bone resorption. FASEB J. 2020;34(2):2392-2407. doi: 10.1096/fj.201902227R.

Xu C, Vitone G, Inoue K, Ng C, Zhao B. Identification of a novel role for Foxo3 isoform2 in osteoclastic inhibition. Journal of Immunology, 2019 Oct 15;203(8):2141-2149. *Featured cover article in the Journal of Immunology 2019

Nakano S, Inoue K, Xu C, Deng Z, Syrovatkina V, Vitone G, Zhao L, Huang XY, Zhao B. G-protein Gα13 functions as a cytoskeletal and mitochondrial regulator to restrain osteoclast function. Scientific Report, 2019 Mar 12;9(1):4236.

Inoue K, Deng Z, Chen Y, Giannopoulou E, Xu R, Gong S, Greenblatt MB, Mangala LS, Lopez-Berestein G, Kirsch DG, Sood AK, Zhao L, Zhao B. Bone protection by inhibition of microRNA-182. Nature Communications, 2018 Oct 5;9(1):4108.
*Featured in Nature Communications Editors' Highlights 2018
*Highlighted by Editorial Commentary: Fassan M, Vicentini C. Role of microRNA-182 in skeletal diseases: new therapeutic approaches to prevent bone loss. Non-coding RNA Investig 2019;3:9.

Binder N, Miller C, Yoshida M, Inoue K, Nakano S, Hu X, Ivashkiv L, Schett G, Pernis A, Goldring SR, Ross FP, Zhao B. Def6 restrains osteoclastogenesis and inflammatory bone resorption, Journal of Immunology 2017 ;198(9):3436-3447.

Miller C, Smith S, Elguindy M, Zhang T, Xiang J, Hu X, Ivashkiv LB, Zhao B. RBP-J-regulated miR-182 promotes TNF-a-induced osteoclastogenesis. Journal of Immunology 2016, 196(12):4977-86. *Featured in the Journal of Immunology 2016

Li S, Miller C, Giannopoulou E, Hu X, Ivashkiv L , Zhao B. RBP-J imposes a requirement for ITAM-mediated costimulation of osteoclastogenesis. Journal Clinical Investigation. 2014 Nov 3;124(11):5057-73.
*Featured on the NIAMS home page as the June 2015 Spotlight on Research:
http://www.niams.nih.gov/News_and_Events/Spotlight_on_Research/2015/ra_bone_loss.asp

Zhao B, Takami M, Yamada A, Wang X, Koga T, Hu X, Tamura T, Ozato K, Choi Y, Ivashkiv LB, Takayanagi H, Kamijo R. Interferon regulatory factor 8 regulates bone metabolism by suppressing osteoclastogenesis. Nature Medicine 2009; 15: 1066-1071.
*Highlighted in the article "Bone diseases: Interferon regulatory factor-8 suppresses
osteoclastogenesis" in Nature Reviews Rheumatology 6, 73-74 (February 2010)
*Recommended by Faculty of 1000 Medicine on Oct 9, 2009.
*Highlighted in the Bulletin Board of Int. J. Clin. Rheumatol. 2009, 4, 5.

For more publications, please see the PubMed listing

Selected Presentations

Invited Speaker, "A non-canonical, RANKL-independent pathway drives inflammatory osteoclastogenesis", Advances in Mineral Metabolisms (AIMM), Snowmass, Colorado, April 2022

Invited Seminar, "When the Bone Meets Inflammation", Icahn School of Medicine at Mount Sinai, New York, June 2022

Invited Seminar, "Non-canonical Mechanisms Drive Inflammatory Osteoclastogenesis", University of Pennsylvania School of Medicine, April 2022

Invited Speaker, "Molecular Regulation of Type-1-Interferon to Regulate Osteoblasts and Osteoclasts", American College of Rheumatology (ACR) Convergence, San Francisco, CA, Nov 2021

Invited Seminar, "Endogenous type-I IFN signaling in osteoblasts and osteogenesis", University of Missouri-Kansas City, June 2021

Spotlight Speaker, "Type-1-Interferon in osteoblasts and osteogenesis", American Society for Bone and Mineral Research Member Spotlight Series, May 2021

Invited featured Seminar, "FoxO3 is a novel type-I IFN activator", Immunity and Immunochemistry conference, Oct 2020

Invited Seminar, "FoxO3 Isoform2: A Novel Player in IFN-I Activation and Osteoclastic Inhibition", North Carolina University, November 2019

Invited Seminar, "Mechanisms of inflammatory osteoclastogenesis and bone resorption", Northwestern University, June 2018

Invited speaker, "MicroRNAs control osteoclastogenesis and bone remodeling", Seventh International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems, Greece, June 2018