Martin Lotz, MD
Professor
Department of Molecular and Cellular Biology
Research Focus
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.
Select Publications
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Fisch, K. M.; Gamini, R.; Alvarez-Garcia, O.; Akagi, R.; Saito, M.; Muramatsu, Y.; Sasho, T.; Koziol, James A.; Su, Andrew; Lotz, Martin K. Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis. Osteoarthritis Cartilage 2018, 1531-1538.
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Transcriptional coactivator PGC-1 alpha regulates chondrogenesis via association with Sox9. Proceedings of the National Academy of Sciences of the United States of America 2005, 102, 2414-2419.
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Alvarez-Garcia, O.; Matsuzaki, T.; Olmer, M.; Miyata, K.; Mokuda, S.; Sakai, D.; Masuda, K.; Asahara, Hiroshi; Lotz, Martin K. FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration. Aging Cell 2018, 17.
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Miyaki, S.; Lotz, Martin K. Extracellular vesicles in cartilage homeostasis and osteoarthritis. Current Opinion in Rheumatology 2018, 30, 129-135.
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Alvarez-Garcia, O.; Matsuzaki, T.; Olmer, M.; Plate, L.; Kelly, J. W.; Lotz, Martin K. Regulated in development and DNA Damage response 1 deficiency impairs autophagy and mitochondrial biogenesis in articular cartilage and increases the severity of experimental osteoarthritis. Arthritis & Rheumatology 2017, 69, 1418-1428.
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Matsuzaki, T.; Akasaki, Y.; Olmer, M.; Alvarez-Garcia, O.; Reixach, Natalia; Buxbaum, Joel N.; Lotz, Martin K. Transthyretin deposition promotes progression of osteoarthritis. Aging Cell 2017, 16, 1313-1322.
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Akagi, R.; Akatsu, Y.; Fisch, K. M.; Alvarez-Garcia, O.; Teramura, T.; Muramatsu, Y.; Saito, M.; Sasho, T.; Su, Andrew; Lotz, Martin K. Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-ß signaling in chondrocytes. Osteoarthritis and Cartilage 2017, 25, 943-951.
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