Rheumatology

Sherry L. Thornton, PhD

Appointment

Assistant Professor of Pediatrics

Email

sherry.thornton@cchmc.org

Phone

513-636-1318

Fax

513-636-3328

Credentials

BS: Biology / Genetics, Ball State University, Muncie, Indiana

PhD: Developmental Biology Program
University of Cincinnati, College of Medicine, Cincinnati, OH

Postdoctoral Research Fellow:Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Research

Angiogenesis plays a major role in autoimmune arthritis. Cellular proliferation within the synovium results in tissue starvation and subsequent angiogenesis to maintain nutrient delivery and gas exchange to the growing pannus tissue. Within this growing pannus are also activated cells that secrete chemokines for recruitment of inflammatory cells into the joint. Activated endothelium within blood vessels also secretes inflammatory cytokines and allows infiltration of inflammatory cells, both of which contribute to disease processes. Therefore, the angiogenic process itself augments the inflammatory response. Certain molecules have been identified that can stabilize the vasculature, such as Angiopoietin1 (Ang1).

Our recent microarray analysis identified the increased expression of a molecule homologous to Ang1, angiopoietin like 4 (Angptl4), which is anti-apoptotic for endothelial cells. Expression of Angptl4 correlates with arthritic disease in both humans and a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA), suggesting a novel role for this protein in arthritis. Our long-term goal is to determine the role of Angptl4 in angiogenic processes related to arthritic disease. Our studies address the hypothesis that Angptl4 inhibits apoptosis of vascular endothelial cells in the arthritic joint by acting through an endothelial cell specific receptor, resulting in the increase or stabilization of newly formed vasculature and subsequent enhancement of inflammatory responses. Targeting angiogenesis either by itself or in combination with other therapies has great potential for therapy of autoimmune arthritis.

Research Grants and Contracts

1 RO1 AR49822 (Jay Degen, Ph.D., PI)
NIH/NHLBI
"Arthritic Disease and the Hemostatic System"
Co-investigator: Sherry Thornton, PhD

Arthritis Foundation Investigator Grant (Thornton, PI)
Arthritis Foundation
"The role of fibrinogen/angiopoietin related protein in autoimmune arthritis"

Trustee Grant (Thornton, PI) 07/01/03 – 06/30/04
CCHMC (internally reviewed)
"Functional Role for FARP in Arthritis and Angiogenesis"

1 P01 AR048929-01A1 (David Glass, PI) 08/22/03 – 07/31/08
NIH/NIAMS
"Gene Expression in Pediatric Arthritis"
Project 4: "Gene Expression Profiles in Systemic Onset Juvenile Rheumatoid Arthritis and Macrophage Activation Syndrome" (Alexei Grom, PI) (Thornton, Co-I)

P30 AR47363 03/01/01-02/28/06
NIH/NIAMS
Pediatric Rheumatic Disease Core Center
Principal Investigator: Susan D. Thompson, PhD
Core: Flow Cytometry Core
Core Director: Sherry Thornton, PhD

Publications, Most Recent

Thornton, S., K.A. Kuhn, F.D. Finkelman and R. Hirsch. 2001. NK cells secrete high levels of IFN-gamma in response to in vivo administration of IL-2.Eur J Immunol 31:3355-3360.

L. Zuo, C.M. Cullen, M.L. DeLay, S. Thornton, L.K. Myers, E.F. Rosloniec, G.P. Boivin, and R. Hirsch. 2002. A single-chain class II MHC-IgG3 fusion protein inhibits autoimmune arthritis by induction of antigen specific hyporesponsiveness.J. Immunol. 168:2554-2559.

Yang L, Thornton S, and Grom AA. 2002. IL-15 inhibits SNP-induced apoptosis of synovial fibroblasts and vascular endothelial cells.Arthritis Rheum, 46:3010-3014.

Thornton, S. D. Sowders, B. Aronow, D.P. Witte, H.I. Brunner, E.H. Giannini and R. Hirsch. 2002. DNA Microarray analysis Reveals Novel Gene Expression Profiles in Collagen Induced Arthritis.Clinical Immunology. 105:155-168.

Katakura, S., K. Jennings, S. Watanabe, E. Adachi, S. Thornton, G. Gao, J.M. Wilson, H. Burstein, B. Trapnell, and R. Hirsch. 2004. Recombinant adeno-associated virus preferentially transduces human, compared to mouse, synovium: implications for arthritis therapy.Mod. Rheumatol. 14: 18-24.

Presentations, Most Recent:

Experimental Biology 2001, Orlando, FL, March 31-Apr. 4, 2001. Thornton, S., K. A. Kuhn, G.P. Boivin, A. A. Grom, R. Hirsch. Collagen-induced arthritis in C3H/He mice: potential influence of IL-2 gene polymorphism on disease susceptibility.

2001 American College of Rheumatology National Meeting, San Francisco, CA. Nov., 2001. Thornton, S., Sowders, D., Aronow, B. and R. Hirsch. Gene expression profiling of early and late murine collagen induced arthritis.

Experimental Biology 2002. New Orleans, LA, April, 2002. Sowders, D., Thornton, S., Aronow, B., Witte, D., and R. Hirsch. Follistatin gene expression is upregulated in murine collagen induced arthritis.

Immunology 2003, Denver, CO, May 6-10, 2003. L.M. Hermann, D. Sowders, D.P. Witte, R. Hirsch and S. Thornton. Expression of a Novel Angiogenic Factor in Autoimmune Arthritis.

Experimental Biology 2004, Washington, DC, April 17-22, 2004. M. Pinkerton, K. Jennings, L.M. Hermann and S. Thornton. Angiopoietin-like 4 exacerbates collagen-induced arthritis and increases the phosphorylation of Akt in mouse endothelial cells.

Hermann, L.M., L. Yang, M. Pinkerton, A. Grom, D. Sowders, D.P. Witte, R. Hirsch, and S. Thornton. 2005. Angiopoietin-Like-4 is a Potential Angiogenic Mediator in Arthritis.Clinical Immunology. (115(1):93-101).