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Leonard Louis Dragone, MD, PhD

Affiliate
Department of Pediatrics
Integrated Department of Immunology
Denver's Top Doctors 2011 - 5280 magazine
America's Top Doctors 2012 - US News & World Report and Castle Connolly Medical, Ltd.

Profile
Office Information

Profile

Conditions Treated

Juvenile Rheumatoid Arthritis (JIA)
Lupus (Systemic Lupus Erythematosus)
Systemic Sclerosis (Scleroderma)
Systemic Vasculitis

Research Areas

Autoimmunity/Rheumatology
Basic Immunology
Pediatric Rheumatology

Programs & Services

Gender:: Male

Education & Training

Education

1996: University of Rochester, Rochester New York, MD, PhD

Residency

1996-1999: University of California, San Francisco, Pediatrics
1999-2000: University of California San Francisco, Pediatric Chief Resident

Fellowship

2000-2003: University of California, San Francisco

Special Interests

Research Interests

Rheumatoid arthritis (RA) is a systemic condition affecting approximately 1% of the general population leading to progressive arthritis and extra-articular manifestations (ExRA), including interstitial lung disease (RA-ILD). The RA-ILD manifestations become more prevalent as RA progresses despite the use of therapies, which effectively treat the arthritis. We have developed a new mouse model to define the mechanisms leading to RA-ILD and discover unique biomarkers, which could predict the development and lead to earlier treatment of patients with RA-ILD.

We also are studying how pregnancy impacts maternal antigen-presenting cells (APCs) and therefore T-cell function to establish new insights into the mechanism by which pregnancy suppresses RA. The knowledge gained from these studies should increase our capacity to manipulate the immune system to treat both the articular and extra-articular manifestations of RA. We are accomplishing the goals of these studies through basic investigation using novel mouse models we generated as well as translational studies using samples from subjects with RA, RA-ILD, and controls.

We also are pursuing new strategies to manipulate lymphocyte-signaling pathways to treat autoimmune disease. We are defining how alterations in ubiquitinylation as well as neddylation alter signaling through the T-cell receptor (TCR) complex in mouse models of inflammatory arthritis to determine their role in autoimmune pathogenesis. We have shown that the loss of an adaptor of the E3 ubiquitin ligase c-Cbl leads to the enhanced develop and function of Tregs, which suppress the development of arthritis in the SKG mouse model. We has also shown that a neddylation inhibitor decreases the threshold for TCR signaling leading to enhanced IL-2 production in T cells and the arrest of progression of arthritis in SKG mice. We are actively defining the mechanisms that govern these observations with the goal of our studies providing foundational support for developing drugs to target ubiquitination and/or neddylation to treat autoimmune disease.

Board Certification

Pediatrics, Pediatric Rheumatology

Affiliations with the University of Colorado Denver

My primary academic appointments are in the Department of Pediatrics at University of Colorado Denver and Colorado Children's Hospital, with secondary appointments in the Department of Pediatrics and the Integrated Department of Immunology at National Jewish Health.

Professional Memberships

AAAS, AAP, ACR, AAI, CARRA

Publications

Peterson, L., Wells, D., Shaw, L.A., Harbeck, R., Valez, M.G., and Dragone, L.L. Novel method for quantitative ANA measurement using near-infrared imaging. J Immunol Methods. 2009 Sep 30;349(1-2):1-8.

Dragone, L.L*, Shaw, L.A., Myers, M.D., and Weiss, A. SLAP, a regulator of immunoreceptor ubiquitination, signaling, and trafficking. Immunological Reviews. 2009; Nov 232: 218–228. (*Corresponding author)

Dragone, L.L, Myers, M.D., White, C., Sosinowski, T, and Weiss, A. (2006) SRC-like adaptor protein regulates B cell development and function. J. Immunol. Jan 1;176(1):335-45.

Myers, M.D., Sosinowski, T., Dragone, L.L., White, C., Band, H., Gu, H., and Weiss, A. (2006) Src-Like Adaptor Protein regulates TCR expression on thymocytes by adapting c-Cb l to the TCR complex. Nature Immunology. Jan;7(1):57-66.

Wang H, Holst J, Woo SR, Guy C, Bettini M, Wang Y, Shafer A, Naramura M, Mingueneau M, Dragone LL, Hayes SM, Malissen B, Band H, Vignali DA. Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T-cell development. EMBO J. 2010 Feb 11. PMID: 20150895

Liontos, L.M., D. Dissanayake, P.S. Ohashi, A. Weiss, L.L. Dragone, and C.J. McGlade. 2011. The Src-Like Adaptor Protein Regulates GM-CSFR Signaling and Monocytic Dendritic Cell Maturation. The Journal of Immunology. Feb 15;186 (4):1923-33. PMID: 21220694.

Peterson, L.K., L.A. Shaw, A. Joetham, S. Sakaguchi, E.W. Gelfand, and L.L. Dragone. 2011. SLAP Deficiency Enhances Number and Function of Regulatory T Cells Preventing Chronic Autoimmune Arthritis in SKG Mice. The Journal of Immunology. Feb 15;186 (4):2273-81.PMID: 21248251

LA Shaw, AL Stefanski, LK Peterson, KK Rumer, A Vondracek, TL Phang, S Sakaguchi VD Winn and LL Dragone. Pregnancy Amelioration of Arthritis in SKG Mice Corresponds with Alteration in Serum Amyloid A3 levels. 2012. American Journal of Clinical and Experimental Immunology (accepted).

SF Friend, LK Peterson, RM Kedl and LL. Dragone. SLAP deficiency increases TCR avidity leading to altered repertoire and negative selection of cognate antigen-specific CD8+ T cells. 2012. Immunologic Research (accepted).