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Leland Shapiro, MD

Associate Professor
 

Phone: (303) 399-8020 (X2837)
E-mail:leland.shapiro@ucdenver.edu
Address: Denver Veterans Affairs Medical Center
Dept. of Medicine, Div. of Infectious Diseases
Box 111L
1055 Clermont Street
Denver, CO 80220

Medical School
University of Massachusetts
Worcester, MA

Residency
University of North Carolina at Chapel Hill
Chapel, Hill, NC

Fellowship
Tufts New England Medical Center
Boston, MA

Leland Shapiro, M.D. research interest is in alpha 1 antitrypsin (AAT), the most abundant serine protease inhibitor in the circulation, posesses inhibitoory effects in vitro or in vivo for several viruses (including HIV) and bacteria (including TB). AAT also appears to function as an endogenous inhibitor of inflammatory cytokines (such as TNF and IL-1), and inhibits in vitro and in vivo synthesis of nitric oxide and apoptosis. AAT inhibits anthrax toxin induced cytolytic activity by 100%, and In an in vivo model of murine islet cell allograft rejection, AAT blocked rejection when used as a single agent. We continue to expand our understanding of the biological activities of AAT. A primary focus is isolating the molecular target of AAT biological activity in an effort to understand the pleitropic functions of AAT and to design novel therapeutic drug candidates to exploit the therapeutic potential of AAT-like molecules.

We also investigate the antiretroviral activity of interleukin(IL) 18 in HIV production in vitro. In a companion clinical investigation of early HIV infection, we are examining the role of constitutive and stimulated whole blood IL-18 content in progression of HIV infection. IL 18 is a cytokine that likely initiates and sustains the Th1 like response, and is a potent inducer of interferon gamma production in vitro and in vivo.

1) Shapiro L, Heidenreich KA., Meintzer M-K, Dinarello CA. Role of p38 mitogen activated protein kinase in human immunodeficiency virus type 1 production in vitro. Proc Natl Acad Sci USA, 95:7422-7426, 1998.

2) Shapiro L, Puren AJ, Barton HA, Novick D, Peskind RL, Shenkar R, Gu Y, Su MS-S, Dinarello CA. Interleukin 18 stimulates human immunodeficieanct virus type 1 in monocytic cells. Proc Natl Acad Sci USA, 95: 12550-12888, 1998.

3) Angel JB, Jacobson MA, Skolnik PR, Giordano M, Shapiro L, LeBeat A, Greaves W, Fuchs AC. A multicenter, randomized, double-blind, placebo-controlled trial of recombinant human interleukin-10 in HIV-infected subjects. AIDS, 14:2503-2508, 2000.

4) Shapiro L, Pott GB, Ralston AH. Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1. FASEB J, 15:115-122, 2001.

5) Chan E, Ralston AH, Shapiro L. Does reduced alpha-1-antitrypson activity account for the link between cigarette smoking and idiopathic pulmonary fibrosis? Chest, 129:72S-74S, 2001.

6) Choi H J, Dinarello CA, Shapiro L. Interleukin-18 inhibits human immunodeficiency virus type 1 production in peripheral blood mononuclear cells. J Infect Dis, 184: 560-568, 2001.

7) Lewis EC, Shapiro L, Bowers OJ, Dinarello CA. Alpha1-Antitrypsin monotherapy prolongs islet allograft survival in mice. Proc. Natl. Acad. Sci .USA. 102:12153-12158, 2005).

8) Sailer CA, Pott GB, Dinarello CA, MaWhinney S, Forster JE, Larson-Duran JK, Landay A, Al-Harthi L, Schooley RT, Benson CA, Judson FN, Thompson M, Palella FJ, Shapiro L. Whole blood interleukin-18 level during early HIV-1 infection is associated with reduced CXCR4 coreceptor expression and interferon-γ levels. J. Infect. Dis. 195:734-738, 2007.

9) Pott GB, Sailer CA, Porat R, Peskind RL, Fuchs AC, Angel JB, LeBeaut A, Grint PC, Dinarello CA, Shapiro/Leland UserEffect of a four-week course of interleukin-10 on cytokine in a placebo-controlled stud of HIV-1-infected subjects. European Cytokine Network. IN PRESS.

10) Chan ED, Kaminska AM, Gil W, Chmura K, Feldman NE, Bai X, Floyd CM, Fulton KE, Huitt GA, Strand MJ, Iseman MD, Shapiro L. Alpha-1-antitrypsin (AAT) anomalies are associated with lung diseases due to rapidly growing mycobacteria and AAT inhibits Mycobacterium abscessus infection of macrophages. Scandinavian J. Infect. Dis. IN PRESS.