Assistant Professor, Department of Medicine, Weill Medical College of Cornell University
Assistant Scientist, Arthritis and Tissue Degeneration Program, Hospital for Special Surgery
Park-Min KH, Antoniv TT, and Ivashkiv LB. Regulation of macrophage phenotype by long-term exposure to IL-10. Immunobiology 2005; 210(2-4):77-86. PMID:16164014
Park-Min KH, Serbina NV, Yang W, Ma X, Krystal G , Neel BG, Nutt SL, Hu X, and Ivashkiv LB. FcγRIII-dependent Inhibition of Interferon-γ Responses Mediates Suppressive Effects of Intravenous Immune Globulin. Immunity 2007; 26(1):67. PMID: 17239631
Yarilina A, Park-Min KH, Antoniv T, Hu X and Ivashkiv LB. Tumor necrosis factor activates an IRF1- dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon response genes. Nature Immunology 2008. 9(4):378 PMID: 18345002
Hu Y*, Park-Min KH *, Yarilina A and Ivashkiv LB. Regulation of STAT Pathways and IRF1 During Human Dendritic Cell Maturation by TNFα and PGE2. Journal of Leukocyte Biology 2008. 845(5) 1453. PMCID: PMC2567899 * co-first author
Ji J.-D. Park-Min KH, and Ivashkiv LB. Expression and Function of Semaphorin 3A and Its Receptors in Human Monocyte-derived Macrophages. Human Immunology 2009. 70(4):211-7. PMID:19480842
Park-Min KH, Ji JD, Antoniv T, Reid AC, Silver RB, Humphrey MB, Nakamura M, Ivashkiv LB. IL- 10 suppresses calcium-mediated costimulation of receptor activator NF-kappa B signaling during human osteoclast differentiation by inhibiting TREM-2 expression. J Immunol. 2009. 183(4):2444-55. PMCID:PMC2742169
Ji JD, Park-Min KH, Shen Z, Fajardo RJ, Goldring SR, McHugh KP, Ivashkiv LB. Inhibition of RANK expression and osteoclastogenesis by TLRs and IFN-gamma in human osteoclast precursors. J .Immunol. 2009. 183(11):7223-33. PMCID:PMC2783334
Lee BNR, Kim TW, Hun JB, Yoo DH, Woo JH, Choi SJ, Lee YH, Song GG, Sohn JW, Park-Min KH, Ivashkiv LB, Ji JD. Direct inhibition of human RANK+ osteoclast precursors identifies a homeostatic function of IL-1β. J Immunol. 2010. 185(10): 5926. PMCID: PMC3016227
Kalliolias GD, Zhao B, Triantafyllopoulou A, Park-Min KH, Ivashkiv LB. Interleukin-27 inhibits humanosteoclastogenesis by abrogating RANKL-mediated induction of nuclear factor of activated T cells c1 and suppressing proximal RANK signaling. Arthritis Rheum. 2010. 62(2):402-13. PMCID:PMC2822027
Wang L, Gordon RA, Huynh L, Su X, Park-Min KH, Han J, Arthur JS, Kallioias GD, and Ivashkiv LB. Indirect inhibition of Toll-like receptor and type I interferon responses by ITAM-coupled receptors and integrins. Immunity 2010. 32(4); 518-530. PMCID:PMC2862476
Ivashkiv LB, Zhao B, Park-Min KH, Takami M. Feedback inhibition of osteoclastogenesis during inflammation by IL-10, M-CSF receptor shedding, and induction. Ann NY Acad Sci. 2011. 1237:88-94. PMCID:PMC3262822
Park SH, Park-Min KH, Chen J, Hu X and Ivashkiv LB. Tumor necrosis factor induces GSK3 kinase-mediated cross tolerance to endotoxin in macrophages. Nature Immunology 2011. 12(7):607. PMCID:PMC3258532
Huynh L, Wang L, Shi C, Park-Min KH, and Ivashkiv LB. ITAM-coupled receptor inhibit IFNR signaling and alter macrophage responses to TLR4 and Listeria monocytogenes. J Immunol. 2012. 188(7): 3447. PMCID:PMC3311708
Issuree PD, Maretzky T, McIlwain DR, Monette S, Qing X, Lang PA, Swendeman SL, Park-Min KH, Binder N, Kalliolias GD, Yarilina A, Horiuchi K, Ivashkiv LB, Mak TW, Salmon JE, Blobel CP. iRHOM2 is a critical pathogenic mediator of inflammatory arthritis. J Clin Ivest. 2013. 123 (2):928. PMCID:PMC3561822
Lee A, Qiao Y, Grigoriev G, Chen J, Park-Min KH, Park SH, Ivashkiv LB, Kalliolias GD. TNFα induces sustained signaling and a prolonged and unremitting inflammatory response in synovial fibroblasts. Arthritis Rheum. 2013. 65(4):928. PMID:23335080
Park-Min KH*, Lee EY*, Moskowitz NK, Lim E, Lee SK, Lorenzo JA, Huang C, Melnick AM, Purdue PE, Goldring SR, and Lione LB. Negative Regulation of Osteoclast Precursor Differentiation by CD11b and β2 Integrin-BCL6 Signaling. JBMR 2013. 28(1):135. PMCID:PMC3522783* co-first author
Park-Min KH, Elisha Lim, Min Joon Lee, Sung-ho Park, Eugenia Giannopoulou, Anna Yarilina, Marjolein van der Meulen, Baohong Zhao, Nicholas Smithers, Jason Witherington, Kevin Lee, Paul-Peter Tak, Rab Prinjha and Lionel B. Ivashkiv. Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation. Nature Communication. 2014. 5:5418. PMID:25391636
For more publications, please see the PubMed listing.
Bone erosion is one of the key clinical features of rheumatoid arthritis (RA) and other types of chronic arthritis and thus has become an important feature in the diagnosis of RA. Bone erosion has been shown to start early in RA disease progression; in fact, articular bone erosion can be detected a few weeks before the onset of RA. The major cell type responsible for bone erosion is osteoclasts, the bone-resorbing cells. This suggests that the components involved in osteoclast formation/differentiation are important players in the destructive processes of inflammatory bone diseases. Therefore, much attention has been devoted to studying the molecular mechanisms of osteoclast formation, function, and activity, resulting in the identification of several therapeutic targets for the treatment of pathological bone resorption, such as RANKL and NFAT. We are interested in:
1) understanding the molecular and epigenetic regulation of osteoclast differentiation in physiological and pathologic conditions,
2) identifying novel regulators of osteoclastogenesis, and
3) testing whether therapeutic targeting of these novel regulators represent a potential treatment for inflammatory bone diseases.
These studies will allow us to identify novel molecules and pathways that can be regulated as part of new strategies for suppressing osteoclastogenesis and pathologic bone resorption in human inflammatory diseases such as RA.
Proteolysis pathways by ADAM17/TACE (TNF a-converting enzyme) in osteoclast differentiation
Since drugs that inhibit TNF are extremely beneficial in the treatment of RA, TACE is considered to be a therapeutic target in RA. However, aside from processing TNF, TACE is also involved in the processing of several other important players in RA. We have found that TACE-mediated proteolysis pathway plays an important role in osteoclastogenesis and have identified a novel pathway that is regulated by TACE. We are currently testing the role of this new pathway in the pathogenesis of inflammatory bone diseases.
Epigenetic regulation of human osteoclast differentiation
Another area of interest is understanding the epigenetic regulation and underlying epigenetic mechanisms in the early stage of human osteoclast differentiation. Epigenetic regulation is a key molecular mechanism by which environmental influences and cues are imprinted on DNA/chromatin and determine patterns of gene expression, responses to environmental challenges, and disease causation and pathogenesis. Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Mutations or abnormal expression of chromatin regulators have been identified in several cancers and have been shown to be a switch that transforms normal cells to disease-associated cells. Interestingly, a large number of these proteins are druggable, and many chromatin regulators are enzymes or ‘readers’ that can be targeted by conventional small molecule approaches. We have investigated the role of epigenetic regulation in osteoclasts and have demonstrated that targeting an epigenetic molecule in osteoclasts can be effective in suppressing the pathological bone resorption that occurs in inflammatory settings such RA. We will further expand our findings to identify various epigenetic targets and underlying mechanisms by which epigenetic molecules regulate osteoclastogenesis. We believe that our studies open up a new line of investigation in the understanding and therapeutic targeting of pathological bone resorption.
One of the goals of Hospital for Special Surgery (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.
As of March 26, 2015, Dr. Park-Min reported no financial interest relationships with healthcare industry.
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, HSS’ Conflicts of Interest Policy does not permit payment of royalties on products developed by him/her that are used on patients at HSS.