Martin Lotz, MD

Professor
Department of Molecular Medicine
California Campus



Research Focus

Our research interest is in joint biology, joint aging, arthritis pathogenesis, preclinical and clinical drug development.

Since 1989 Dr. Lotz directed a program on joint aging and osteoarthritis. Our studies identified aging-related changes in cartilage and other joint tissues that determine risk for osteoarthritis.

We discovered that cellular homeostasis mechanisms are compromised in aging and that this represents an early event leading to tissue damage.We initiated a ‘Joint Omics’ project which uses next generation sequencing technologies to uncover aging and disease associated changes in the transcriptomes in joint tissues. Data from this project are being used to identify key regulators of the abnormal phenotypes of cells, with focus on transcription factors.

Our current studies address the role of FOXO, KLF and MKX transcription factors and the circadian rhythm pathway in cartilage homeostasis and osteoarthritis pathogenesis. These transcription factors are also being investigated in meniscus, ligaments and spine. Efforts are ongoing to discover small molecules and genetic approaches to target transcription factors in the treatment of joint diseases and in tissue engineering.


Education

M.D. (Medicine), Heidelberg University, 1981

Professional Experience

1997-               Professor, Molecular Medicine (MM), The Scripps Research Institute
1990-1996       Associate Professor,  Department of Medicine, University of California
1987-1990       Assistant Professor, Molecular and Experimental Medicine, Scripps Clinic and Research Foundation1997-2017 Professor, Molecular and Experimental Medicine (MEM), Scripps Research
1990-1996 Associate Professor, Molecular and Experimental Medicine (MEM), Scripps Research
1987-1990 Assistant Professor, Molecular and Experimental Medicine (MEM), Scripps Research

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

All Publications

Fisch KM, Gamini R, Alvarez-Garcia O, Akagi R, Saito M, Muramatsu Y, Sasho T, Koziol JA, Su AI, Lotz MK. Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis. Osteoarthritis Cartilage 2018; 26:1531-8.

Alvarez-Garcia, O., Matsuzaki, T, Olmer, M, Miyata, K., Mokuda, S, Sakai, D., Masuda, K, Asahara, H, Lotz, MK. FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration Aging Cell 2018; 18:e12800.

Miyaki, S, Lotz, MK. Extracellular vesicles in cartilage homeostasis and osteoarthritis Current Opinion in Rheumatology 2018; 30:129-135.

Matsuzaki T, Alvarez-Garcia O, Mokuda S, Nagira K, Olmer M, Gamini R, Miyata K, Akasaki Y, Su AI, Asahara H, LOTZ MK. FoxO transcription factors in cartilage maturation, homeostasis and osteoarthritis pathogenesis. Science Transl Med 2018; 10:eaan0746.

Alvarez-Garcia O, Matsuzaki T, Olmer M, Plate L, Kelly JW, LOTZ MK. Regulated in development and DNA damage response 1 deficiency impairs autophagy and mitochondrial biogenesis in articular cartilage and increases severity of experimental osteoarthritis. Arthritis Rheumatol 2017; 69:1418-1428.

Matsuzaki T, Akasaki Y, Olmer, Oscar M, Alvarez-Garcia O, Reixach N, Buxbaum J, LOTZ MK. Transthyretin deposition promotes progression of osteoarthritis. Aging Cell 2017; 16:1313-1322.

Akagi R, Akatsu Y, Fisch KM, Alvarez-Garcia O, Teramua T, Muramatsu Y, Saito M, Sasho T, Su A, LOTZ MK. Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-β signaling in chondrocytes. Osteoarthritis Cartilage 2017; 25:943-951.

Hasegawa A, Yonezawa T, Taniguchi N, Otabe K, Akasaki Y, Matsukawa T, Saito M, Neo M, Marmostein LY, LOTZ MK. Fibulin-3 in joint aging and osteoarthritis pathogenesis. Arthritis Rheumatol 2017; 69:576-585.