Our Research

Driven by Powerful Imaging

  • Traumatic Fractures and Sports Injuries

  • Blast/Burn Injury

  • Traumatic Spinal Cord Injury

Our Problem

Patients are affected by trauma induced heterotopic ossification from a variety of injuries and surgical procedures. HO is found in >65% of blast/burn injury, 20-80% of joint replacement, 20% of traumatic fractures and sports, and 20% of traumatic spinal cord injury patients.

  • Some of Our Models

  • Increased Vascularity around HO

Strategies & Results

Our variety of models have and continue to facilitate our elucidation of key steps along a convoluted HO pathway. Some findings include increased vascularity and vessels in regions of increased heterotopic ossification. To share our experimental results, we rely on a myriad of imaging techniques including micro CT, immunohistochemistry, and immunofluorescence.

Burn + Tenotomy Model

Our fundamental trauma model consists of a concomitant dorsal burn and achilles tendon tenotomy. This model reliable produces HO at the local tenotomy site and nearby environments.

Inducible Geneotype

Many of our experiments rely heavily on inducible gene technology. Using Cre recombinase and lox-P site technology, we can create robust models whose genes of interest can be turned on and off at will.

Genetic Recombination

Stemming from our inducible gene schema, combined permutations expand our scope and types of interrogations we can apply to our HO pathway.

Collaborative Spaces

Micro CT Reconstructions

Micro CT reconstruction is a foundational component of much of our research allowing us visualization for exploration of our models and quantifying HO growth.

Heterotopic Ossification

Early diagnosis and Prevention strategies

As many as 65% of our severely combat-injured service members will go on to develop heterotopic ossification (HO), a musculoskeletal disorder characterized by the formation of mature bone in soft tissues including muscle, tendon, ligaments and fascia. As a complication of trauma, HO presents the most important barrier to functional recovery and independence.Furthermore, over 60% of civilian major burn patients and over 50% of joint replacement surgery patients develop HO, with risks that only increase after subsequent operations.  The pervasive nature of HO extending across several tissue types suggests that treatment directed to a specific tissue may be ineffective, whereas therapy directed towards centrally acting pathways may be more effective.  Once bone forms around a joint, patients develop debilitating joint contractures and loss of mobility. Surgical excision of HO can be attempted to restore function, but patients with periarticular HO rarely regain complete range of motion, with contractures due to persistent or recurring HO.  Current medical strategies to prevent de novo or recurrent HO including glucocorticoids, bisphosphonates, and non-steroidal anti-inflammatory medications either have significant side effects and/or uncertain impact, possibly because they fail to target key pathways involved in HO formation.  In addition to effective therapies, methods of identifying potential HO patients prior to radiographic diagnosis are needed to target early intervention to a population that is likely to benefit.  Given the burden of HO disease in these populations, its high morbidity and suboptimal treatments, there is substantial need for early diagnosis and therapy to inhibit HO by targeting its causative processes.

Fibrodysplasia Ossificans Progressiva

One of the Earliest Clues

Fibrodysplasia ossificans progressive (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification, a congenital disorder that mirrors our topic of focus.  Subsequent studies of this parallel disease have elucidated biochemical pathway steps and agents such as the ALK2 receptor. ALK2 mutations have now been well described to play a role in patients with (FOP), and recent studies have implicated ALK2 as playing a more central role in cartilage condensation that can lead to subsequent bone formation in unwanted areas. Establishing more links of this nature is a powerful strategy in localizing relevant agents.

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