Timothy M. Griffin, Ph.D.
Adjunct Assistant Professor, Department of Biochemistry and Molecular Biology and Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center
Obesity is a major risk factor for osteoarthritis, the most common form of arthritis and a leading cause of disability in the U.S. Although conventional wisdom holds that increased pressure on joints from carrying excess weight causes osteoarthritis, this is far from a complete answer. Recent discoveries suggest that fat itself is a critical mediator of the disease. Fat is not just excess energy from food hanging around your waist. Rather, fat can act like an organ and deregulate the body’s inflammation response chemically.
My lab is studying how obesity contributes to the development of osteoarthritis by studying how changes in joint pressure and inflammation associated with excess fat contribute to the inflammatory process. We are also studying how these changes impact the metabolic machinery of tissues within the joint, such as cartilage. Understanding how excess fat alters both joint stress and inflammation, we believe, will help paint a more complete picture of how obesity contributes to arthritis.
In addition to studying the relationship between arthritis and obesity, we’re also looking at a third component—exercise. Pain caused by osteoarthritis keeps people from leading active lifestyles. This then contributes to obesity, which often leads to worsening pain in the joints. We want to better understand this vicious cycle and find out if there’s a way to break it, allowing people to be more active, reduce obesity and live without the pain of arthritis.
B.A., Harvard University, Cambridge, MA, 1996
Ph.D., University of California, Berkeley, CA, 2002
Postdoc, Biological Anthropology & Anatomy, Duke University Medical Center, Durham, NC, 2002–2004
Postdoc, Orthopaedic Bioengineering, Duke University Medical Center, Durham, NC, 2004–2007
Honors and Awards
1994 Academic All-Ivy League, Harvard University
2000 National Science Foundation, Dissertation Improvement Grant
2000 Graduate Research Fellowship, UC Berkeley Department of Integrative Biology
2003 New Investigator Award, American Physiological Society
2004 NIH Ruth L. Kirschstein National Research Service Award (NIAMS)
2004 NIH Institutional Postdoctoral Training Fellowship (NIBIB)
2007 Outstanding Postdoc Award, Duke University
2007 Young Investigator Award, Osteoarthritis Research Society International (OARSI) World Congress on Osteoarthritis
2007 Hulda Irene Duggan Arthritis Investigator Award, Arthritis Foundation
2010 Top 10 Arthritis Advances, Arthritis Foundation
2010 Melba M. O’Connell Memorial Fellow, Arthritis National Research Foundation
Advisory Editor, Arthritis & Rheumatology
American Physiological Society
Orthopaedic Research Society
Osteoarthritis Research Society International
Society for Free Radical Biology and Medicine
Joined OMRF Scientific Staff in 2008.
Osteoarthritis is a disease characterized by cartilage destruction and abnormal bone growth resulting in joint pain and severe disability. It is the primary cause of disability in the United States, and it contributes significantly to reductions in health that occur with aging. Although osteoarthritis is often considered an inevitable consequence of aging, numerous genetic and environment risk factors have been identified that mediate its occurrence and severity. One of the most significant and modifiable risk factors is obesity.
Our laboratory uses integrative and interdisciplinary approaches to study how obesity dysregulates biomechanical, inflammatory, and metabolic processes that are associated with the development of osteoarthritis. We are seeking to determine how dietary fats, adipokines (e.g., leptin), and altered joint loading regulate articular cartilage homeostasis via effects on chondrocyte mitochondrial function and free radical biology. We are particularly interested in the role of nitric oxide as a signaling molecule for genes that regulate cell metabolism and oxidative stress responses, such as peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α).
We are also interested in understanding how physical activity interacts with obesity-related phenotypes to regulate these processes in healthy and diseased tissue. Therefore, we use a variety of models spanning multiple levels of organization (e.g., cell, tissue, and animal) to study the effect of voluntary exercise (in vivo) and controlled biomechanical loading regimes (in vitro) on inflammatory, metabolic, and anti-oxidant processes in cartilage.
By studying the interaction of diet and physical activity (i.e., two modifiable risk factors for obesity), we hope to reveal novel pathways that regulate cartilage matrix homeostasis. Furthermore, by examining behavioral outcomes in our animal models that are associated with altered motor function and pain, we seek to identify the pathologic mechanisms linking obesity to clinically relevant outcome measures. These studies will also provide a basis for examining how therapeutic interventions that target inflammatory and oxidative processes affect joint-specific pathophysiology and behavioral outcomes.
* Zhao Y, Ling F, Griffin TM, He T, Towner R, Ruan H, Sun XH. Up-regulation of the Sirt1 and PCG-1alpha genes in white adipose tissue of Id1 deficient mice: implications in the protection against diet and age-induced glucose intolerance. J Biol Chem 2014. [Abstract] EPub
Cai A, Hutchison E, Hudson J, Kawashima Y, Komori N, Singh A, Brush RS, Anderson RE, Sonntag WE, Matsumoto H, Griffin TM. Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice. Osteoarthritis Cartilage 2014. [Abstract] EPub
* Yao L, Heuser-Baker J, Herlea-Pana O, Zhang N, Szweda LI, Griffin TM, Barlic-Dicen J. Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity. FASEB J 2014. [Abstract] EPub
Issa RI, Griffin TM. Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation. Pathobiol Aging Age Relat Dis 2:17470, 2012. [7 pages]
Griffin TM, Huebner JL, Kraus VB, Yan Z, Guilak F. Induction of osteoarthritis and metabolic inflammation by a very high fat diet in mice: Effects of short-term exercise. Arthritis Rheum 64:443-453, 2012. [Abstract]
Griffin TM, Fermor B, Huebner JL, Kraus VB, Rodriguiz RM, Wetsel WC, Cao L, Setton LA, Guilak F. Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice. Arthritis Res Ther 12:R130, 2010. Abstract
Griffin TM, Huebner JL, Kraus VB, Guilak F. Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum 60:2935-2944, 2009. Abstract
Allen KD, Griffin TM, Rodriguiz RM, Wetsel WC, Kraus VB, Huebner JL, Boyd LM, Setton LA. Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen. Arthritis Rheum 60:2684-2693, 2009. [Abstract]
Hanna JB, Schmitt D, Griffin TM. The energetic cost of climbing in primates. Science 320:898, 2008. Abstract
Free Radical Biology and Aging Research Program, MS 21
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7579
Fax: (405) 271-1437