Researchers within the Musculoskeletal Research Focus Area have a multi-level understanding of musculoskeletal anatomy, function and pathology. Our research focuses on three critical areas of musculoskeletal biology:
- the cellular and molecular mechanisms underlying development, aging, and repair of bone and cartilage,
- the musculoskeletal biomechanics of swallowing, chewing, and locomotion, from both disease-oriented and evolutionary perspectives, and
- the evolution of major vertebrate groups, including whales and birds, incorporating an evolutionary developmental biology perspective.
Development, aging and repair of bone cartilage
Fayez Safadi, Ph.D., Director
More than 50 million Americans have osteoporosis and low bone density, placing them at increased risk for osteoporosis. Studies suggest that approximately one in two women and up to one in four men age 50 and older will break a bone due to osteoporosis. The Osteolab focuses on novel therapies for osteoporosis and bone regeneration for fractures and spinal fusion. Dr. Safadi’s lab also studies metabolic bone diseases such as age/estrogen deficiency-induced osteopenia, osteopetrosis, inflammation and cartilage-associated diseases (rheumatoid and osteoarthritis arthritis and fracture repair). The goal of our research is to understand the pathological mechanisms underlying various bone and cartilage diseases to develop strategies for the therapeutic management of such diseases. We identified a novel growth factor (named Osteoactivin) that has anabolic effects on bone. Ostoeacitivn could be used as potential therapeutic agent to stimulate bone formation in diseases associated with osteopenia, spinal fusion and increased risk of fracture. Our lab is also investigating the role of Osteoactivin as an antiinflammatory and neuroprotective factor in neurodegenerative diseases.
Lisa Cooper, Ph.D.
The Cooper lab investigates age-related changes in the skeletons of long-lived bats. Bats as a group are unique in that their bones bend with wingbeats and they display superb resistance to fracture. The Cooper lab is currently investigating how bats maintain and renew this fl exible matrix for bioengineering applications. In addition, the Cooper lab’s molecular, biomechanical and structural results shows that bats are unusual in that their wing bones lack age-related bone fragility. The Cooper lab is currently investigating the molecular mechanisms driving the prevention of age-related bone fragility in bats. Genes of bats that were identified as critical to the maintenance of bone integrity in bats replaced those of mice in cell culture studies. The Cooper lab aims to modify the cells of elderly mice such that they produce a more youthful bone matrix that lacks vulnerabilities that typically lead to fragility diseases.
Tariq Haqqi, Ph.D.
Dr. Haqqi’s group focuses on developing new treatment modalities for degenerative joint diseases such as osteoarthritis. Aging is a major factor for chronic diseases including osteoarthritis, a leading cause of joint dysfunction associated with cartilage degradation, disability and poor quality of life in the affected population worldwide. Among adults 60 years of age or older the prevalence of symptomatic knee osteoarthritis is approximately 10 percent in men and 13 percent in women. There are no disease-modifying medical therapies currently available for osteoarthritis. The ultimate objective of our research program is to address this unmet need by identifying and validating novel compounds and their target molecules in chondrocytes, the only cell type present in the cartilage, that can inhibit induction and/or limit the progression of osteoarthritis. In addition, the group is also studying epigenetics in cartilage and the potential of plant derived inhibitors that will be most effective in suppressing joint damage. These research projects are funded by the NIH/National Institutes of Arthritis and Musculoskeletal Diseases and the NIH/National Center for Complementary and Integrative Health.
Rebecca German, Ph.D.
Dr. German’s lab works on understanding the biomechanics and pathology of neural control of swallowing using an animal model. Swallowing difficulties, and the failure to protect the airway, are a major cause of health problems in premature or preterm infants. The neurological cause for these problems is unknown, and as a result there are few effective therapies. Understanding the mechanism of airway protection failure will provide a biological basis for decisions about care and intervention in these fragile and cherished patients. Another focus in the lab is the impact of Parkinson’s disease (PD) on
feeding, swallowing and airway protection. PD patients suffer from many effects of compromised eating, such as reduced nutrition and chronic aspiration. These problems are hard to diagnose because patients do not report them and they require invasive imaging to be seen.
Christopher Vinyard, Ph.D.
Dr. Vinyard’s laboratory aims to understand the evolution of the primate head. Specifi cally, the Vinyard lab is interested in understanding how specific activities, such as chewing or biting, affect the morphology and evolution of the skull and face of primates. Most of this work considers the physiology of feeding behaviors, examining the ecology and physiology of wild primates and the evolutionary genetics of musculoskeletal form.
Jesse Young, Ph.D.
Locomotion is central to all that animals do. What factors determine how fast an animal can sprint, how efficiently it can travel, or how well it can balance? Dr. Young’s lab studies the biomechanics of the locomotor system in mammals from an evolutionary perspective. More specifi cally, we investigate how the anatomy and the physics of the external world that constrain locomotor performance in mammals, and how these constraints determine the capabilities of an animal trying to survive in its natural world.
Vertebrate Evolution & Evolutionary Developmental Biology
Tobin Hieronymus, Ph.D.
Research in the Hieronymus lab aims to understand the musculoskeletal anatomy and function of bird wings. Birds have dramatically altered the common components of the forelimb to respond to the functional demands of flight. Within this system, our research addresses three basic questions: (1) what are the morphological adaptations that allow birds to fl y so efficiently (or, what can we learn from birds about building wings)? (2) how have birds modifi ed basic tissues such as bone and ligament to adapt to new forms of loading (what can bird bones teach us about material design)? (3) how has the evolution of different avian flight styles and capabilities played out over evolutionary time (some wing morphology is adaptive for specific types of flight, some may be phylogenetic inertia—which parts are which)? Our lab addresses these questions using novel techniques that bridge the gap in scale between standard gross anatomy and histology, as well as modeling and analysis approaches that allow us to leverage the diversity of living and fossil birds as a broad pool of natural experiments.
Hans Thewissen, Ph.D.
Whales and dolphins are among the most unusual of mammals, and, even though their ancestors lived on land, have developed perfect adaptations to life in water. The lab of Dr. Hans Thewissen studies these adaptations as they may inspire innovative solutions to human health problems. For instance, bowhead whales are osteoporotic as juveniles, but fully recover by the time they reach adulthood. And when a whale dives, its intraocular pressure increases ten-fold, but is not liable to glaucoma, a leading cause of blindness due to increased pressures in humans. Samples of modern whales are collected in Alaska, and the lab studies ancient whale ancestors in Pakistan and India.