​Timothy Griffin, Ph.D.

Education

Postdoctoral Fellow 2007, Duke University Medical Center, Durham, NC

PhD 2002, University of Berkeley, Berkeley, CA

​​BA 1996,  ​Harvard University, Cambridge, MA

​Research Overview

​Osteoarthritis is the primary cause of disability among adults in the United States, resulting in a substantial decline in health and mobility. The two greatest risk factors for osteoarthritis are aging and obesity. Our laboratory uses many different approaches to study how aging and obesity alter metabolic, inflammatory, and biomechanical processes that cause the development of osteoarthritis. For example, we are studying how dietary fats, fat-related hormones, and joint loading damage cells that grow and repair cartilage. We are particularly interested in the role of sirtuins (e.g., Sirt3) as regulators of cellular metabolism, mitochondrial function, and oxidative stress responses to protect against osteoarthritis during aging and obesity.

In addition, we are investigating how fat tissue in joints can contribute to synovial inflammation by altering the metabolic environment of the joint. This research focusses on the role of physical activity in regulating immuno-metabolic coupling of synovial macrophages. We use a variety of genetically modified mouse models to study the effect of voluntary exercise and controlled biomechanical loading on post-traumatic joint inflammation and pain. By studying the interaction of diet and physical activity during aging, we hope to reveal novel pathways that regulate cartilage health and joint inflammation. Furthermore, by examining behavioral changes in our animal models that measure function and pain, we emphasize clinically relevant outcome measures so that we can better translate our finding to patients.

Research Focus

​​Griffin Lab

Timothy Griffin, Ph.D.

​Principal Investigator

​Padmaja Mehta D’souza, Ph.D.

​Staff Scientist

​Albert Batushansky, Ph.D.

​Assistant Staff Scientist

​Ravi Komaravolu, Ph.D.

​Postdoctoral Fellow

​Shouan Zhu, Ph.D.

​​Postdoctoral Fellow

​Taylor Block, B.S.

​Senior Research Technician

​Dominic Cortassa, B.S.

​Research Technician

​Anita Jopkiewicz, B.S.

​Research Trainee

​Kamil Kobak, M.S.

​Research Trainee 

​Contact

​Oklahoma ​Medical Research Foundation

​Aging & Metabolism Research Program

​Chapman Building, S-202 & S-203

Oklahoma City OK 73104

​Phone: ​(405) 271-7549

​​​​​tim-griffin@omrf.org​​

Publications

​NCBI​

​Website

​Link

Aging and Osteoarthritis: Cartilage oxidation is a central feature of OA pathology, but the age-related mechanisms underlying its etiopathogenesis are poorly understood. We recently discovered that aging impairs the specific activity of the mitochondrial antioxidant SOD2 due to a decline in the mitochondrial deacetylase SIRT3.  This work implicates mitochondrial acetylation as a critical mediator of chondrocyte redox regulation and cartilage matrix homeostasis. We are using mouse genetic models to conditionally delete or over-express SIRT3 in cartilage. These studies will allow us to determine in vivo how SIRT3 regulates age-dependent declines in cartilage stress resilience and metabolic dysfunction. An additional goal is to identify the cartilage proteolytic enzymes that are activated under these conditions of increased mitochondrial acetylation and inflammation.

 

Obesity and Osteoarthritis: Obesity is among the most significant and preventable risk factors for developing osteoarthritis (OA). Efforts to identify the causes of this risk have traditionally focused on obesity-induced triggers of joint stress, such as mechanical and inflammatory factors. Indeed, our previous work has shown that leptin is a key mediator of the link between adiposity and OA. However, we know little about how obesity impairs chondrocyte cellular defense mechanisms resulting in inappropriate or insufficient responses to joint stresses. Recent studies indicate an unexpected role for chondrocyte lipid metabolism in regulating cartilage development and adult tissue remodeling using genetically modified mouse models. We are testing the hypothesis that a high fat diet increases chondrocyte lipid metabolism, resulting in increased acetyl-CoA production and mitochondrial acetylation with increasing age. We are utilizing transcriptomic, proteomic, and metabolomic methods to characterize obesity-related changes in chondrocyte metabolism in vivo.