Neuropathy is associated with skeletal disorders including osteoporosis, fractures, and general bone loss. However, our understanding of the region-specific mechanisms surrounding this is limited by our lack of comprehensive maps of skeletal innervation in health and disease. To overcome this, we use tissue clearing, light sheet and confocal microscopy-based approaches to mapping and quantifying nerves in and on the bone, and within the surrounding periosteum and muscle.
Neural regulation of bone marrow adipose tissue (BMAT)
Approximately 70% of the bone marrow is actually made up of a unique adipose tissue depot known as the bone marrow adipose tissue (BMAT). Nerves in bone connect BMAT to peripheral adipose tissue depots through the central nervous system, with regulatory circuits at the level of both the spinal cord and brain, in addition to local signaling events between nerve terminals and individual adipocytes. In this project, we’re working to understand how neural regulation of BMAT controls local energy storage and release and how this contributes to relationships and cell function within the nerve-fat-bone axis. This has important implications for both whole body energy partitioning and local regulation of skeletal homeostasis. We’re currently looking for a graduate student or post-doc that would be interested in working on this project.
Wireless biosensing for monitoring of bone turnover and neural activity
Through a collaboration with Drs. Srikanth Singamaneni and Shantanu Chakrabarrty, we’re working to develop a wireless biosensing platform for use in the oral cavity to monitor periodontal disease status, progression, and resolution after treatment. Moving forward, we’d like to find someone that is interested in adapting this technology toward monitoring neural activity and neurotransmitter release. Please contact us if you’re interested.
Extracellular regulation of nerve extension in and around bone
This project focuses on the Schwann cell and it’s ability both interact with the ensheathed nerve axon and to make and secrete large quantities of extracellular proteins. We hypothesize that these interactions are critical for regulation of nerve extension and function within the skeletal microenvironment, impacting diverse outcomes including bone formation, repair, and skeletal pain.
Impact of acute and chronic neural stimulation on bone
Using direct application of electrodes or wireless cuff-based technologies, we apply acute and chronic stimuli to peripheral nerves which connect to the skeleton. This allows us to study the impact of neurostimulation on bone turnover, cell function, and protein secretion in diverse settings of health and disease.
Peripheral neuropathy as a component of diabetic skeletal disease
Diabetes is associated with decreased bone quality and increased fracture risk in both rodents and humans. We’ve found that the range of potential human skeletal phenotypes is particularly striking (see image above, mid-diaphysis of the human 1st metatarsal in a healthy (top) and diabetic individual (bottom)). In this project, we’re interrogating neuropathy as a component of diabetic skeletal disease using human samples and rodent models.
We’ll work with you to customize and develop your project based on your ideas, expertise, and interests while leveraging our ongoing work to provide a strong foundation.
- Extracellular regulators of skeletal innervation and repair. Current emphasis is on the study of periostin. Techniques include working with rodent and human samples, high-resolution imaging, fracture/loading, molecular biology, skeletal phenotyping, and dental biology/tooth movement. Possible candidates include trainees at the graduate or post-doctoral level (BME, neurobiology, cell biology, etc).
- Neural regulation of bone marrow adipose tissue expansion and function in health and disease. These investigations build upon our extensive previous publications in this area to define novel regulators of BMAT function and its integration with bone health and peripheral metabolism. Areas of interest include high-resolution imaging, bone/adipose tissue biology, neurobiology, physiology and metabolism, molecular biology, use of rodent and human samples and beyond. Possible candidates include trainees at the graduate or post-doctoral level (neurobiology, physiology, endocrinology, cell biology, etc).
- Peripheral neuropathy as a determinant of musculoskeletal health in adolescents with type 1 diabetes. This is a new clinical project in collaboration with pediatric endocrinology and the bone health clinic at Washington University. Project includes collection and analysis of human data pertaining to bone health (Xtreme CT II) and nerve-muscle-bone interactions in young patients with diabetes. Serial image registration techniques will be developed to augment your interpretation of disease pathogenesis (‘virtual histomorphometry’). Possible candidates include BME graduate students, clinical research fellows (endocrinology, bone health, or pediatrics), and post-doctoral fellows.