The Musculoskeletal Research Group focuses on three critical areas of musculoskeletal biology:
- the cellular and molecular mechanisms underlying the development, aging, and repair of bone and cartilage,
- the biomechanics of swallowing, chewing, and locomotion, from both disease-oriented and evolutionary perspectives, and
- the evolution and evolutionary developmental biology of major vertebrate groups.
Regulation of bone cell development and function, with specific emphasis on growth factors that can enhance osteogenesis
Bone loss is a major health care problem in the United States and worldwide. Risk factors associated with osteoporosis, include estrogen-deficiency (post-menopuasal) and aging. During bone development and its maintenance, the antagonistic processes of bone formation and resorption are regulated by various systemic and local factors (hormones, growth factors, cytokines, etc). It is evident that bone formation during skeletal modeling/remodeling and fracture repair requires stringent control of osteoblast proliferation and differentiation. Regulation of these biological processes involves sequential expression of cell growth and tissue specific genes in response to different regulatory signals.
Dr. Safadi’s research laboratory focuses on the regulation of bone cell development and function, with specific emphasis on growth factors that can enhance osteogenesis. We are interested in various metabolic bone diseases such as age/estrogen-induced osteopenia, osteopetrosis and cartilage-associated diseases (osteoarthritis and rheumatoid arthritis). The goal of our research is understand the pathological mechanisms underlying various bone diseases in order to develop strategies for the therapeutic management of such diseases. We identified a novel growth factor (named Osteoactivin) that has anabolic effects on bone. If we understand the mechanisms responsible for this effect, then this factor could be used as potential therapeutic agent to stimulate bone formation in diseases associated with osteopenia, increased risk of fracture and spinal fusion.
In addition, we developed an interest on the role of osteoactivin (gpnmb) as a neuroprotective factor for neurodegenerative diseases such as Parkinson’s disease and Alzheimer disease. This research is conducted in collaboration with the neurodegenerative research group at NEOMED. We also interested on the role of gpnmb as anti-inflammatory factor in acute and chronic conditions for wound healing and neuroinflammation.
Dr. Safadi’s laboratory is also working on another collaborative research with Dr. Mary Barbe at Temple University School of Medicine. Dr. Barbe laboratory utilizes an in vivo model for cumulative trauma disorder that focuses on the molecular and cellular mechanisms associated with tendonitis and inflammation-induced bone loss.
Assistant Professor of Anatomy and Neurobiology
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 flexible 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.
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. In our lab we work on understanding the biomechanics and pathology of neural control of swallowing using an animal model, the baby pig. 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 on feeding, swallowing, and airway protection. Such patients suffer from many effects of compromised eating, such as reduced nutrition and chronic aspiration. These problems hard to diagnose because patients do not report them and they require invasive imaging to be seen. In collaboration with Dr. Jason Richardson, we are carrying out animal model, integrative studies from brain to tongue and jaws, to determine what is going wrong, and how it can be fixed.
Professor of Anatomy and Neurobiology
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.
Evolutionary Morphology of Bird Wings
My research aim is 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, my research addresses three basic questions: (1) what are the morphological adaptations that allow birds to fly so efficiently (or, what can we learn from birds about building wings)? (2) how have birds modified 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)? My 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.
Mammalian Anatomy, Development, and Evolution
Dr. Thewissen’s research centers on the anatomical specializations of whales and combines gross anatomical, histological, embryological, and paleontological methods. The evolution of whales from living on land to living in water as well as the biology of Arctic whales are central stage in the research program. Examples of specific projects include studying whether living whales are deaf by counting nerve cells in their ears, figuring out how old a whale is by studying tree-ring like structures in the skull, and using the fine structure of the teeth to learn about the biology of the animal. Much of the research is based on fossil whales from Pakistan and India, and samples of modern whales from the Alaskan Arctic, both unique resources.
Professor of Anatomy and Neurobiology
Evolutionary and Functional Morphology of the Mammalian Skull
My research aims to understand the relationships between the form, function and evolution of the mammalian head. Specifically, I aim to better understand how certain activities, such as chewing or biting, affect the form and evolution of the skull and face. Most of this work is question driven and falls into one of three research avenues: 1) Physiology and functional morphology, 2) Behavioral and ecological morphology and 3) Comparative morphometrics.
A major component of my research involves studying the physiology of chewing and biting. This involves using in vivo methods, such as electromyography, strain gage approaches and video analysis, to study jaw-muscle activity patterns, facial bone strains and jaw movements during chewing and biting in living animals.
A second research focus involves conducting field studies of primate chewing and biting. In addition to allowing us to assess how well our lab research mimics natural field conditions, this work provides an environmental context for interpreting morphological adaptations in the mammalian head. Recent field work includes studying feeding behaviors in free-ranging howling monkeys at Hacienda La Pacifica, Costa Rica.
Finally, I am interested in comparative analyses of skull and jaw-muscle form among mammals. These comparative studies complement the lab and field research by broadly describing patterns of form-function associations and morphological integration among species and/or age-groups.
Research in the Young Lab focuses on evolutionary, comparative and developmental aspects of mammalian locomotion. Our work is question driven and is currently concentrated on two topics: the biomechanics of arboreal locomotion, particularly in primates, and the interaction between musculoskeletal growth and locomotor development.
A principal focus of the work in the lab has been the biomechanics of arboreal locomotion in primates. The aim of this work is to relate standard biomechanical measures – including gait patterns, joint postures, limb forces and center of mass movements – to fitness-critical variables such as balance, accelerative capacity and energetic efficiency. A variety of techniques are used to address this aim, including three-dimensional motion tracking, measurement of single-limb kinetics and whole-body mechanics using custom-designed force transducers, and morphometric assessments of musculoskeletal anatomy. Our current research focuses on using state-of-the-art techniques to quantify locomotor kinematics in free-ranging primates moving in their natural habitats.
A second focus of our research in the lab has been the degree to which growth and development might be adaptively constrained to promote fitness across the lifespan. Immature mammals must often compete against adults for resources, evade common predators and keep pace during group travel, despite small body size, an underdeveloped musculoskeletal system and other limits on performance. We should expect strong selection for mechanisms that permit young individuals to overcome such limitations and reach reproductive maturity. Previous research has examined how allometric changes in skeletal form and locomotor mechanics might facilitate improved locomotor performance in young mammals. Our current research i is focused on how natural selection has impacted growth and locomotor development in cottontail rabbits, a model system representing fast-growing ecologically challenged mammals.
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