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Martin Lotz, M.D.

Professor
Department of Molecular and Experimental Medicine
California Campus
Laboratory Website
mlotz@scripps.edu
(858) 784-8960

Research Focus

Arthritis Pathogenesis: Development of Novel Diagnostic and Therapeutic Approaches

Arthritis Research investigates the pathogenesis of rheumatoid arthritis and osteoarthritis to develop new diagnostic tools and therapies. The scientific approach includes clinical studies in collaboration with the Divisions of Rheumatology and Orthopedic Surgery at Scripps Clinic, laboratory research on human patient tissues, animal models, cell and molecular biology.

The rheumatoid arthritis research program addresses mechanisms involved in the activation and proliferation of synovial fibroblasts and of mononuclear phagocytes. Gene expression analysis of peripheral blood leukocytes from rheumatoid arthritis patients is used to identify new mediators of the aberrant inflammatory response and predictors of the patients' response to antirheumatic therapy. Intracellular signaling pathways in monocytes and synovial fibroblasts are studied for the identification of novel targets for antirheumatic therapy.

The osteoarthritis research program is focused on mechanisms of joint aging. A multidisciplinary program project analyzes cellular, biochemical and molecular changes that occur in joint aging and represent risk factors for the development of osteoarthritis. Gene expression analysis will document the complete spectrum of genes, termed chondrome, that are expressed by chondrocytes at defined stages of activation and differentiation and in normal aging and osteoarthritic tissues. Several programs are evaluating novel therapeutic approaches in animal models of the disease. Lead candidates that target novel mediators are being prepared for clinical trials. A clinical project on patients with joint trauma who are at risk for early development of osteoarthritis defines sensitive markers to monitor disease progression and efficacy of new therapeutic interventions.

Education

M.D., Medicine, Heidelberg University, 1981

Awards & Professional Activities

Arthritis Foundation Investigator Award 1988
American Society for Clinical Investigation 1994
Board of Directors, Osteoarthritis Research Society International 2000-2008
President, Osteoarthritis Research Society International 2004-2006
Kappa Delta Award, Orthopedic Research Society 2005
Basic Science Award, Osteoarthritis Research Society International 2010

Current Editorial Boards
Arthritis Research Therapy, Associate Editor; Biotherapy; The Journal of Immunology; Osteoarthritis and Cartilage; Modern Rheumatology

Selected References

Taniguchi N, Caramés B, Ronfani L, Ulmer U, Komiya S, Bianchi ME, LOTZ M. Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis. Proc Natl Acad Sci USA 106:1181-6, 2009.

Grogan SP, Miyaki S, Asahara H, D'Lima DD, LOTZ M. Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis. Arthritis Res Ther 11:R85, 2009.

Taniguchi N, Caramés B, Kawakami Y, Amendt BA, Komiya S, LOTZ M. Chromatin protein HMGB2 regulates articular cartilage surface maintenance via beta-catenin pathways. Proc Natl Acad Sci USA 106:16817-22, 2009.

LOTZ M, Kraus V. Posttraumatic Osteoarthritis: Pathogenesis and pharmacological treatment options. Arthritis Res Ther 12:408, 2010.

Otsuki S, Hanson SR, Miyaki S, Grogan SP, Kinoshita M, Asahara H, Wong C-H, LOTZ M. Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways. Proc Natl Acad Sci USA 107:10202-07, 2010.

Caramés B, Taniguchi N, Otsuki S, Blanco F, LOTZ M. Autophagy is a protective mechanism in normal cartilage and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum 62:791-01, 2010.

LOTZ M, Caramés B. Autophagy and cartilage homeostasis mechanisms in joint health, aging and osteoarthritis, Nature Rev Rheumatol 7:579-87, 2011.

Taniguchi N, Caramés B, Cherqui S, Kawakami Y, LOTZ M. Expression patterns and function of chromatin protein HMGB2 during mesenchymal stem cell differentiation. J Biol Chem 286:41489-98, 2011.