ORTHOPAEDIC SURGERY LABS
We are interested in the pathobiolgy of tendon disease - specifically the role of inflammatory mediators on tendon progenitor cells and the subsequent downstream effect on tendon health and disease. Our prior investigations have utilized standard 2D cell culture models, but we have moved towards the development of an in vitro model system which has allowed for the reconstruction of a tendon-like 3D micro-ribbon structure seeded with human tenocytes and progenitor cells. This has allowed us to place physiologic loads on the cells themselves, therefore recreating the normal environment from which tendinopathy originates and allowing us to perform a more detailed investigation of cell response to injury.
By 2030, over two million total hip and knee arthroplasties will be performed in the United States annually. If the incidence of periprosthetic joint infection (PJI) continues to range from 0.5-3% of knee replacements and 0.5-1% of hip replacements, over 30,000 patients each year will be newly diagnosed with a PJI. Currently, the United States spends over $2 billion treating PJI. The gold standard treatment relies on removing contaminated implants followed by extended duration intravenous organism-specific antibiotics. Unfortunately, this gold standard still fails 10-20% of the time. This risk is compounded by the threat of developing antibiotic-resistant bacteria. Moreover, a PJI increases the 1-year risk of death by 5-fold when compared to patients without a PJI. The innate immune system typically responds to virulent bacteria by recruiting polymorphonuclear neutrophils and inflammatory M1-macrophages to the site of infection which phagocytize the bacteria and generate of reactive oxygen species, bactericidal peptides, and neutrophil extracellular traps to clear the bacterial inoculum. Free-floating bacteria can attach to an implant’s surface by expressing proteins that form strong interactions with host extracellular matrix. These sessile bacteria accumulate extracellular DNA via bacterial autolysis – eventually forming a protective biofilm that subverts the innate immune system. Biofilm-associated sessile bacteria survive by environmentally excluding antibiotics, sharing resistance genes, and altering their metabolism to become small-colony variants (SCVs). Dr. Amanatullah is developing novel ways to target SCVs. Staphylococcal SCVs also upregulate expression of an immune checkpoint molecule, programmed cell death ligand 1 (PD-L1), in macrophages. The PD-1/PD-L pathway maintains immune tolerance to self-antigens. Several human malignancies as well as chronic viral and malarial infections to derive a survival advantage via host immunosuppression by co-opting the PD-1/PD-L pathway. Current diagnostic criteria neglect host immunity as a screening criterion prior to primary and revision arthroplasty. Dr. Amanatullah is also trying to understand the host immune response to SCVs to alter therapeutic decision making in PJI.
In the Bhutani lab research interests are driven towards understanding the mechanisms that govern and reprogram stem cell fate during development, regeneration and disease. The long-term goal is to translate these fundamental principles learnt towards musculoskeletal repair and regeneration in the clinic.
The research conducted in the Chu Lab brings the best science in cell biology, regenerative medicine, mechanics, and imaging together to restore and rejuvenate damaged joints, so that people can live full and healthy lives, free of joint pain. Through nearly two decades of research funded by the National Institutes of Health, the Veterans Administration, and the Department of Defense, Dr, Chu and her team has led development of new MRI color mapping techniques and refined new blood testing methods to identify joint aging before OA even starts. Please visit the Chu Lab website to learn more.
FAN YANG LAB
The Fan Yang Lab group seeks to understand how microenvironmental cues regulate stem cell fate, and to develop novel biomaterials and stem cell-based therapeutics for tissue engineering and regenerative medicine.
The Ladd Lab works to improve musculoskeletal conditions, injury, and deformity, with a focus on the hand and upper limb.
In the laboratory,our team investigates cellular and molecular deficiencies in tissue types including tendon, ligament, articular cartilage, and meniscus. By understanding aberrant pathways leading to tissue injury, they can identify innovative therapeutic targets for intervention. In collaboration with the Genetic Engineering and Synthetic Biology laboratories, Dr. Sherman’s research has explored the role of orthobiologic agents such as platelet rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) for tissue healing in patella tendinopathy (the breakdown of collagen in a tendon). Our lab is also investigating the use of CBD for musculoskeletal applications as an alternative to commonly used local anesthetics and cortisone derivatives. In my earlier work, we researched the cellular toxicity of such applications.
THE STUART GOODMAN LAB
Our research is highly interdisciplinary. We work at the interface of immunology, biomaterials, bioengineering and medicine. Our research seeks to understand the mechanisms of various musculoskeletal conditions related to fractures and bone defects, total joint replacement, arthritis, and osteonecrosis etc. based on the cross-talk between cells in the mesenchymal and the hematopoietic lineages.
THE YAO RESAERCH LAB
The Yao Research Laboratory is operated by Wei Le, our lab manager. We are exploring tissue engineering and its role in tendon repairs as well as bone fracture healing. We are also exploring the structural differences of ligaments surrounding the hand joints in the native setting, the traumatic setting and in the presence of Dupuytren's disease. Lastly, we are involved in the innovation and development of minimally invasive treatment options for hand and wrist problems.
The Yang Lab 's research interests are in the areas of biomaterials, implant devices, drug delivery, and musculoskeletal tissue engineering. In particular, we are interested in developing bio-inspired biomaterials and platform technologies to engineer tissues and organs.