Director, Laboratory of Experimental Rheumatology,
The Feinstein Institute for Medical Research
Professor, Elmezzi Graduate School of Molecular Medicine,
North Shore-LIJ Health System
Professor of Molecular Medicine,
Hofstra North Shore-LIJ School of Medicine
Phone: (516) 562-1275
Dr. Percio Gulko is a board-certified rheumatologist, as well as an investigator at the Feinstein Institute for Medical Research and a professor at the Hofstra North Shore-LIJ School of Medicine. His goal is to identify genes implicated in the regulation of severity and joint damage of rheumatoid arthritis (RA), and to generate new targets, as well as the development of more effective therapies. His laboratory has been using a) rodent models of autoimmune arthritis to identify and characterize genes involved in the regulation of arthritis severity and joint damage and b) synovial tissues and cells (fibroblast-like synoviocytes, FLS) from patients with RA to identify genes implicated in cell invasion and articular damage.
Dr. Gulko’s lab has identified several severity and joint damage non-MHC loci. It has also discovered that these arthritis loci operate via the regulation of important phenotypes in disease pathogenesis such as the invasive properties of FLS and the ability of neutrophils to migrate to the inflammatory site. The team has identified new regulators of FLS invasion.
During the past five years, Dr. Gulko has been a principal investigator in three different NIH R01 grants. He has successfully managed these projects, all related to RA pathogenesis, and all led to nearly 60 publications in respected peer-reviewed journals.
Rheumatoid arthritis is a common autoimmune disease that affects nearly 1% of the population and is associated with increased risk for disability, deformities and reduced survival. While a number of new therapies have emerged with encouraging results in recent years, disease remission and cure are still rarely achieved. Therefore, the identification of rheumatoid arthritis severity genes and the understanding of their function are anticipated to generate novel targets for the development of more effective therapies, as well as new tools for diagnosis and prognostication.
In order to accomplish the goals of gene identification, the laboratory has been using a combination of strategies involving genetic analysis, functional studies of inflammatory cells and gene expression studies of the joint cells (synovial fibroblasts). These studies led to the identification of several new chromosomal regions containing genes that regulate arthritis severity as well as the discovery of novel regulators of the synovial inflammatory response and destructive behavior such as the nuclear receptor LXRa and the vitamin D receptor (VDR). Furthermore, Dr. Gulko’s laboratory has determined that one specific arthritis locus, Cia5a, regulates numbers of a unique type of regulatory T cells that are capable of suppressing the immune responses. Cia5a also suppresses the expression of members of the Spleen tyrosine kinase (SYK) pathway.
Two other loci, Cia5d and Cia25, were found to regulate the invasive properties of the joint cells (synovial fibroblast), a characteristic that strongly correlates with joint damage. Gene expression and functional studies determined that part of the Cia5d-mediated effect in arthritis involves the regulation of synovial cell invasion via modulating the production of soluble MT1-MMP, CXCL10 and ezrin-mTOR activation.
Ultimately, these genes, and others currently being studied, should generate novel [novel what? Word appears to be missing] and targets for the development of new and better treatments for rheumatoid arthritis and other erosive forms of arthritis such as psoriatic arthritis. Dr. Gulko’s team is in advanced stages of developing and testing new molecules that interfere with the activity of some of the new therapeutic targets identified in the laboratory.
Max Brenner MD, PhD
Phone: (516) 562-2696
Universidade Federal do Rio Grande do Sul (UFRGS), Brazil
Field of Study: Medicine
Medical College of Georgia, Augusta, GA
Field of Study: Internal Medicine
National Institutes of Health, Bethesda, MD
Field of Study: Rheumatology
1990 Certified, Brazilian Board of Rheumatology, Brazil (Brazilian Rheumatology Association)
1991 Research Award, Birmingham Chapter of the Lupus Foundation of America
1991 Research Award, Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia)
1995 Certified, American Board of Internal Medicine
1997 Research Award, American Autoimmune-related Diseases Association
2000 Certified, American Board of Internal Medicine (Rheumatology)
- Laragione T, Brenner M, Li W, Gulko PS. “Cia5d regulates a new fibroblast-like synoviocyte invasion-associated gene expression signature.” Arthritis Res Ther. 2008 Aug 15;10(4):R92. [Epub ahead of print]
- Laragione T, Brenner M, Mello A, Symons M, Gulko PS. “The arthritis severity locus Cia5d is a novel genetic regulator of the invasive properties of synovial fibroblasts Arthritis Rheum.” 2008 Aug;58(8):2296-306.
- Brenner M, Linge CP, Li W, Gulko PS. “Increased synovial expression of nuclear receptors correlates with arthritis protection: A possible novel genetically-regulated homeostatic mechanism.” Arthritis Rheum. 2011 Oct;63(10):2918-29. doi: 10.1002/art.30507.
- Laragione T, Brenner M, Sherry B, Gulko PS. “CXCL10 and its receptor CXCR3 regulate synovial fibroblast invasion in rheumatoid arthritis. Arthritis Rheum.” 2011 Nov;63(11):3274-83. doi: 10.1002/art.30573.
- Laragione T, Shah A, Gulko PS. “The Vitamin D Receptor Regulates Rheumatoid Arthritis Synovial Fibroblast Invasion And Morphology.” Mol Med. 2012 Mar 27;18(1):194-200. doi: 10.2119/molmed.2011.00410.
- Hu X, Laragione T, Sun L, Koshy S, Jones KR, Ismailov II, Yotnda P, Horrigan FT, Gulko PS, Beeton C. “KCa1.1 potassium channels regulate key pro-inflammatory and invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis.” J Biol Chem. 2012 Feb 3;287(6):4014-22. Epub 2011 Nov 10.
- Jenkins E, Brenner M, Laragione T, Gulko PS. “Synovial expression of Th17-related and cancer-associated genes is regulated by the arthritis severity locus Cia10. Genes Immun.” 2012 Apr;13(3):221-31. doi: 10.1038/gene.2011.73. Epub 2011 Nov 3. PMCID: PMC3339715.
- Brenner M, Laragione T, Shah A, Mello A, Remmers EF, Wilder RL, Gulko PS. “Identification of two new arthritis severity loci that regulate levels of autoantibodies, IL-1β and joint damage.” Arthritis Rheum. 2012 May;64(5):1369-78. doi: 10.1002/art.33468.
- Laragione T, Gulko PS. “Liver X Receptor (LXR) regulates rheumatoid arthritis fibroblast-like synoviocytes invasiveness, MMP-2 activation, IL-6 and CXCL10.” Mol Med. 2012 May 15. doi: 10.2119/molmed.2012.00173. [Epub ahead of print].
- Brenner M, Gulko PS. “The arthritis severity locus Cia5a regulates the expression of inflammatory mediators including Syk pathway genes and proteases in pristane-induced arthritis.” BMC Genomics. 2012 Dec 19;13(1):710. [Epub ahead of print].