SUMMARY
The proposed research project examines the impact of early utilization of a novel neuromuscular electrical
stimulation (NMES) program on skeletal muscle metabolism and overall metabolic health in individuals with
sub-acute, complete spinal cord injuries (SCI).
Background: Individuals with SCI live longer than before and live to an age where metabolic disorders become
highly prevalent. Due to loss of mobility and severe skeletal muscle atrophy, obesity, glucose intolerance, and
peripheral insulin resistance develop soon after the onset of SCI. These abnormalities are thought to contribute
to the increased diabetes disease risk and accelerated aging process in the SCI population. As a result of
these trends, overall burden of complications, economic impact and reduced quality of life are increasing. Until
there are effective treatments for SCI, it is imperative to develop effective interventions to mitigate metabolic
disorders that develop in individuals with SCI. There is a lack of experienced clinicians and researchers who
have expertise on metabolic health and SCI. Additionally, there is a lack of adequate early interventions to
prevent or reduce the degree of metabolic dysfunction that follows injury.
Implications: The growing population and increased age of individuals with SCI calls for novel and
interdisciplinary rehabilitation approaches to care in order to reduce the economic burden and enhance the
quality of life.
Next Steps: Interdisciplinary rehabilitation researchers are needed to lead the investigations necessary to
address the aforementioned problems and challenges. As a candidate for this training and research proposal, I
am uniquely trained and motivated to commit my career to addressing the challenges associated with the
current trends. My prior research and clinical training ideally position me for an independent research career.
During my doctoral and post-doctoral training, I was actively engaged in research on the development of
exercise and nutrition interventions to improve musculoskeletal and metabolic health in individuals with SCI. I
bring to this research a diverse training background in physical therapy and rehabilitation, human physiology,
and skeletal muscle biology as indicated by my publication record. My postdoctoral experience fostered my
abilities to direct truly translational research by extending clinical research experiences to mechanistic studies
in skeletal muscle and molecular biology. The specific focus of my work that I will build upon involved
understanding the effects of NMES on activity of intracellular signaling pathways for glucose utilization and
muscle growth. I conducted all aspects of SCI projects – from subject recruitment, to clinical studies, to
molecular and histological assays in the laboratory. My postdoctoral experiments revealed novel findings,
some of which are detailed in the Research Strategy, providing strong support for the hypotheses of my
proposal. The early results of these experiments show exciting possibilities for a quick and effective increase in
insulin sensitivity and improvements in muscle phenotype in individuals with SCI who have pre-diabetes
without use of medication. My enthusiasm for these findings is based on the potential for prevention.
Through this work, I have found there is much work to be done and that more training in the space between
disciplines (rehabilitation and metabolic disease) will enhance my effectiveness as a rehabilitation researcher.
I seek an NICHD-sponsored K01 award to support investigations of a combined (resistance + aerobic) NMES
training protocol for inducing physiological adaptations necessary to optimize metabolic health in individuals
with sub-acute SCI. In addition, I will use the protected time for training in energy metabolism, metabolomics,
and clinical trial design and implementation. These activities will ultimately prepare me for a productive,
independent career focused on translating findings from basic research into feasible, clinical
interventions to reduce the risk of metabolic disease in the chronic stages of SCI without use of
medication. I am currently in the ideal environment to execute the proposed investigations and have
assembled a mentoring team of renowned scientists in in the disciplines necessary to integrate this
intervention approach. Additionally, I have access to state-of-the-art research laboratories, core facilities and
equipment as well as the ability to recruit patients from a nationally recognized rehabilitation hospital.
The novelty of the proposed project lies in the rigorous examination of the effects a combined (aerobic +
resistance) NMES program on skeletal muscle metabolism and in the application of novel targeted
metabolomics approaches to understand the influence of muscle adaptations on overall metabolic health
immediately after SCI (as opposed to studying deconditioned, chronic SCI). If, as hypothesized, SCI individuals
treated with a combined NMES prescription over the 6 weeks following the injury maintain a healthy muscle
mass and metabolism as well as overall metabolic profile, future intervention efforts can focus on 1)
preventing negative muscle adaptations in the acute stages of SCI, and 2) utilizing home-based
training for life-long maintenance of overall health and quality of life.