photo of Baohong Zhao, PhD

Baohong Zhao, PhD

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About Dr. Zhao

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

Research Institute
Arthritis and Tissue Degeneration Program

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

Credentials

Appointments

Professor, Biochemistry in Medicine, Department of Medicine, Weill Medical College of Cornell University
Professor, Biochemistry in Medicine, Department of Medicine, Graduate Program in Cell & Developmental Biology, Weill Medical College of Cornell University
​​​​​​​Associate Scientist, Arthritis and Tissue Degeneration Program, Hospital for Special Surgery

 

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

Publications by Dr. Zhao

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

Industry Relationships

Industry Relationships

One of the goals of HSS is to advance the science of orthopedic surgery, rheumatology, and related disciplines for the benefit of patients. Research staff at HSS may collaborate with outside companies for education, research and medical advances. HSS supports this collaboration in order to foster medical breakthroughs; however, HSS also believes that these collaborations must be disclosed.

As part of the disclosure process, this website lists Research staff collaborations with outside companies if the Research staff member received any payment during the prior year or expects to receive any payment in the next year. The disclosures are based on information provided by the Research staff and other sources and are updated regularly. Current ownership interests and leadership positions are also listed. Further information may be available on individual company websites.

Below are the healthcare industry relationships reported by Dr. Zhao as of March 28, 2023.

  • American College of Rheumatology (ACR) - Honoraria
  • Texas A&M University College of Dentistry - Honoraria
  • ​​​​​​​University of Pennsylvania - Honoraria

By disclosing the collaborations of HSS Research staff with industry on this website, HSS and its Research staff make this information available to patients and the public, thus creating a transparent environment for those who are interested in this information. Further, the HSS Conflicts of Interest Policy does not permit payment of royalties on products developed by him/her that are used on patients at HSS.

Feel free to ask the Research staff member about their relationship(s).

Dr. Zhao in the News

    • New research from Hospital for Special Surgery Research Institute recently published on July 7th in Nature Communications identifies a new target pathway of inflammatory osteolysis (bone destruction) present in and unique to patients with rheumatoid arthritis.

      Dr. Zhao’s study identified a new pathway in patients with RA that can be stimulated for bone resorption. This pathway provides a new biologic marker that opens avenues for selective treatment of inflammatory osteolysis (bone destruction). This may present an alternative to existing drug treatments that reduce symptoms in rheumatoid arthritis patients, but simultaneously compromise their immune system.

      Inflammatory bone loss is a signature symptom for many RA patients, causing significant pain and leading to loss of function if not properly treated. Until now, the pathways causing these bone damage issues have been poorly understood. Dr. Zhao’s study is the first to identify a molecular program that specifically leads to inflammatory bone degeneration. As inflammatory conditions may trigger as of yet unknown pathways for osteoclast generation, Dr. Zhao and her team from the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery sought to and were successful in identifying a key driver of osteoclastogenic pathways; her team found that transforming growth factor β (TGFβ) priming enables inflammatory cytokine tumor necrosis factor (TNF) to effectively induce osteoclastogenesis and bone erosion.

      “There is an important yet unmet need to discover new therapies for RA patients. With the identification of this mechanism, we can provide novel therapeutic strategies to suppress inflammatory bone loss, while minimizing or mitigating the undesirable effects on bone remodeling or immune response in disease settings,” Dr. Zhao shared. “This opens new avenues for selective treatment of inflammatory osteolysis that may not require the suppression of a patient’s immune system in the process.”

      By identifying the molecular pathway that leads to bone destruction in rheumatoid arthritis, Dr. Zhao’s findings may lead to new treatments that don’t compromise the immune system function of the estimated 1.36 million adults in the U.S. with RA. 

      Part of these findings were retroactive study using datasets from patients with Lupus and Rheumatoid Arthritis. This work was supported by NIH/NIAMS and Rosensweig Genomics Center at the Hospital for Special Surgery from The Tow Foundation.

      Additionally, in a new study published in The Journal of Immunology on November 1, 2023, Dr. Zhao, led the identification of another previously unknown target that can be used as a new pathway in the treatment of RA. This finding is significant as it allows clinicians a new target treatment pathway with the potential to help suppress inflammatory bone erosion that can cause pain, discomfort and disability in patients.

      About HSS Research Institute
      HSS Research Institute is the largest musculoskeletal research facility in the world, comprising 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration.

    • microRNA-based therapeutics may one day help treat bone loss seen in diseases such as osteoporosis and rheumatoid arthritis, according to new research published this week in Nature Communications. The study is the first to identify microRNA-182 as a key regulator of bone health, to provide proof of concept that microRNA-182 inhibitors may be useful to treat certain diseases of the bone, and to show that microRNA-182 may be useful as a biomarker to monitor inflammatory bone diseases.

      "Our study is the first exploration of key RNAs that would be used to develop a microRNA-based therapeutic strategy to treat bone diseases," said principal study investigator Baohong Zhao, PhD, assistant scientist in the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery (HSS), and assistant professor at Weill Cornell Medical College, both in New York City. "Inhibition of microRNA-182 could have very promising therapeutic implications in the future disease treatment of inflammatory bone diseases, such as rheumatoid arthritis."

      Bone destruction is a major characteristic and severe consequence of multiple skeletal diseases, including osteoporosis and inflammatory arthritis. These diseases have a significant impact on patient quality of life and increase the risk of disability.

      MicroRNAs play key roles in a variety of biological and pathological processes and have recently gained increasing clinical attention as promising therapeutic targets or biomarkers. Recent studies support the use of microRNAs for the treatment of cancer, metabolic disorders, and infectious diseases such as hepatitis C virus, but little is known about microRNA’s therapeutic role in bone health.

      "Skeletal diseases, such as postmenopausal osteoporosis and inflammatory arthritis, such as rheumatoid arthritis, are very common," said Dr. Zhao. "We set out to identify novel therapeutic targets to treat these refractory diseases. microRNA-182 came out as the top candidate for playing a role in inflammatory bone diseases, in a genome-wide screening of microRNAs."

      A genome-wide screening of microRNAs identified microRNA-182 as a regulator of inflammatory osteoclast differentiation. The health of the human skeleton depends on a delicate equilibrium between bone resorption by osteoclasts and bone formation by osteoblasts. Bone destruction in rheumatoid arthritis and postmenopausal osteoporosis is mainly attributable to the abnormal activation of osteoclasts.

      In basic science experiments, the researchers demonstrated that deletion of microRNA-182 protects against excessive osteoclastogenesis and bone resorption in models of ovariectomy-induced osteoporosis and inflammatory arthritis. Pharmacological treatment of these diseases with microRNA-182 inhibitors completely suppressed pathologic bone erosion.

      In other experiments, the researchers discovered that the level of microRNA-182 expression in humans is strongly correlated with rheumatoid arthritis. "The data reveal a strongly positive correlation of microRNA-182 expression with rheumatoid arthritis pathogenesis and bone resorption," said Dr. Zhao. "In patients with rheumatoid arthritis, we can see much higher levels of this microRNA-182 than in healthy donors."

      The researchers also evaluated microRNA-182 levels in 10 patients with rheumatoid arthritis and found anti-inflammation treatment controlled the disease and significantly decreased microRNA-182 levels, returning them to healthy donor levels. "Our promising data indicate that inhibition of microRNA-182 could not only have therapeutic implications," said Dr. Zhao. "microRNA-182 could be also used as a biomarker to track disease progress and potentially the benefits of treatments."

      This research was supported by the National Institutes of Health.

  • Researchers Identify New Signaling Pathway Thought To Play Role In Rheumatoid Arthritis
  • HSS: New Cell Signaling Pathway Important In RA
  • Researchers Identify Protein Involved in Causing Gum Disease, Osteoporosis, Arthritis
  • HSS Scientists Identify New Cell Signaling Pathway Thought to Play Key Role in Rheumatoid Arthritis