Current Students


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Jordan Borrell

Grad Student, Department of Bioengineering

Project Title: Topographical Mapping of the Outputs to Hindlimb Muscles using Intraspinal Microstimulation

Research Mentor: Randolph Nudo
Paul Arnold

Spinal cord injury (SCI) is a major cause of paralysis caused by motor vehicle accidents, sports related injuries, and war and combat injuries affecting over 6 million people in the world. To date there are few effective treatments to reduce paralysis and return movement. However, the future looks bright. With the purpose of inducing movement in the muscles below the spinal cord lesion, a stimulating electrode will be inserted into the gray matter of the spinal cord, a procedure known as intraspinal microstimulation (ISMS). Aided with innovative research into new technologies, a computer will be interfaced with the central nervous system.  This type of treatment could greatly improve the quality of life for millions of Americans every year.

The objective of my research is to further the development of the brain-computer-spinal cord (BCSC) interface device, being developed between our laboratory and our collaborators at Case Western University, by implementing a rat model to develop a three-dimensional map of the outputs to hindlimb muscle movement within the T13-L2 area of the spinal cord and deriving the relationship between the ISMS-evoked EMG potentials from the muscle and the resulting hindlimb movement. This research is necessary to advance the development of the novel BCSC device and give us the data for stimulation site placement of the final BCSC device.

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Linda D'Silva
Grad Student, Department of Rehabilitation Science

Project Title: To study the impact on the vestibular system in type 2 diabetes and acute concussion

Research Mentor: Patricia Kluding
Hinrich Staecker

The human vestibular system plays an important role in gaze stability and maintenance of balance. The peripheral sensory apparatus of the vestibular system comprises of the semicircular canals and otoliths which are motion sensors. While the semicircular canals detect angular acceleration; the otoliths play an important role in detecting linear acceleration.  Both sensory organs are damaged by various disease processes; both acute and chronic in nature. The main purpose of my study is to compare the effect of two distinct disease processes on the peripheral vestibular system, specifically the otolith organs. I will study how type 2 diabetes, a chronic condition, and an acute injury like a concussion affect the otoliths. Once that baseline information is collected, I will look at specific interventions to rehabilitate the otolith organs in the peripheral vestibular system and assess how the two disease states respond to vestibular rehabilitation. 


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Anna Mattlage
Grad Student, Department of Physical Therapy and Rehabilitation Science

Project Title: The role of exercise on inflammatory biomarkers and IGF-1 levels following an acute stroke.

Research Mentor:  Sandra Billinger
Co-Mentor: Doug Wright

Description: Stroke is the leading cause of death and disability for older adults in the United States with approximately 795,000 new or current strokes occurring each year.  New and innovative intervention strategies that mitigate disability and improve functional outcomes are essential for improving the lives of stroke survivors.  People after stroke who have lower levels of inflammation and higher serum values of insulin-like growth factor 1 (IGF-1) have been shown to have better outcomes.  Furthermore, exercise is a potent stimulus that may facilitate a reduction in inflammation and improve circulating IGF-1 levels following stroke.  The goals of this project are to: 1) characterize the effects of exercise on circulating levels of inflammatory markers and IGF-1 and 2) determine whether exercise initiated during the acute stage of recovery demonstrates neuroprotective effects and improves neurorehabilitation outcomes.  This project could have a significant impact on the therapeutic effects of exercise in clinical practice, rehabilitation research, and improve quality of life for the survivors of stroke.

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Jason-Flor Sisante
Grad Student, Department of Physical Therapy and Rehabilitation Science

Project Title: The effect of exercise on brain blood flow, cognitive performance, and neurovascular biomarkers following acute stroke

Research Mentor: Sandra Billinger
Co-Mentor: John Stanford

Stroke survivors exhibit altered blood flow and cerebral autoregulation, specifically on the ipsilateral side of the stroke.  Poor regulation of brain blood flow may impair delivery of oxygen and nutrients to the parenchema and could affect cognitive performance.  In non-stroke populations, previous research has shown that exercise improves blood flow and cognition, but not much is known about the effects of exercise on brain blood flow and cognition following acute stroke. Using transcranial Doppler ultrasound, cognitive batteries, and a submaximal exercise protocol, this project will investigate the effects of exercise during acute stroke recovery on brain blood flow, cognitive performance, and neurovascular biomarkers. This work may elucidate whether cerebral blood flow regulation and cognition improves as a result of exercise early after stroke.  We will also examine neurovascular markers that may be associated with changes in our outcome measures. This work has important implications for acute stroke rehabilitation and may help improve patient-centered outcomes.

Isabella Fuentes

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Isabella Fuentes
Grad Student, Department of Anatomy and Cell Biology

Project Title: Early life stress and voluntary exercise on comorbid mood and urogenital pain disorders in male mice

Research Mentor: Julie A. Christianson
Co-Mentor: Tomas L. Griebling

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urological diagnosis for men under age 50, and the third most common for those over 50. Despite this high prevalence rate, the underlying pathophysiology of and optimal treatment strategies for CP/CPPS remain to be elucidated. CP/CPPS is frequently comorbid with other functional pain disorders, including irritable bowel syndrome, interstitial cystitis/painful bladder syndrome, migraine, and fibromyalgia, and is also commonly diagnosed alongside mood disorders, including anxiety and depression. Exposure to adverse childhood events has a lasting impact on the hypothalamic-pituitary-adrenal axis and serves as risk factors for mood and functional pain disorders. In the clinical setting, exercise has a beneficial impact on depression and anxiety, as well as decreased associated perceptions of pain; however, to our knowledge, exercise has not been investigated as a potential intervention for urogenital pain disorders. The long-term objective of this project is to understand how exercise can lessen the impact of early life stress on comorbid chronic pelvic pain syndromes and psychological disturbances in male mice that can lead to translation into the human condition. 

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Max Murphy
Grad Student, Department of Bioengineering

Project Title: Describing spike-timing dependent synaptic modification for use with a rehabilitative brain-computer interface

Research Mentor: Randolph Nudo

The brain's plasticity allows it to establish new networks that facilitate recovery of function following injury. Plasticity is reliant on the timing and coordination of action potentials. Our lab has previously demonstrated the ability to artificially create pathways in the brain using a closed-loop system for intracortical microstimulation (ICMS) based on the timing of these action potentials. This technique has been effective in restoring reaching behavior in rats following traumatic brain injury to the motor cortex. In order to generalize this type of treatment to other areas of the brain and to other model systems, we need to better understand its governing electrophysiological mechanisms. Does the same closed-loop timing for ICMS facilitate recovery between different areas of the brain? What kind of changes in action potential timing occur as a result of using ICMS and are these changes reliant on the detected action potentials that are used as the closed-loop trigger? Is it more advantageous to use multiple single-units when triggering closed-loop ICMS? These are among the questions that remain in an exciting and largely unexplored field, and ones to which I hope to find answers during the course of my research.

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Matt Stroh
Grad Student, Neuroscience

Project Title: Understanding the role of iron homeostasis and mitochondrial function in a mouse model of neurodegenerative disease and diabetes

Research Mentor: Hao Zhu
Co-Mentor: Doug Wright

Alzheimer's disease can be characterized by a gradual decline in cognition and the ability to perform daily functions such as task planning and speaking. Mounting evidence suggests that mitochondrial function plays a large, if not central, role in Alzheimer's and other neurodegenerative diseases. Interestingly, a diet high in medium chain triglycerides (fats) and low in both protein and carbohydrates (ketogenic diet) has been shown to improve symptoms in neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease.  This is interesting in that ketone bodies are a preferred source of fuel for the brain, strongly implicating a role for mitochondrial function and metabolism in the pathogenesis of these diseases.  I have designed and begun work on a minor project that aims to help elucidate the role of electron transport chain (ETC) dysfunction in brain aging and neurodegeneration.  I am utilizing a previously described, endogenous pathway to deliver exogenous, engineered transcripts to mitochondria in a brain specific manner.  These transcripts serve as either non-coding, anti-sense RNAs targeted against mitochondrial transcripts that act as translational blockers/terminators resulting in decreased availability of critical ETC components (namely Complex I and Complex IV), or functional mRNAs encoding mutated or otherwise dysfunctional ETC subunits. The novelty behind this approach is the ability to localize and translate exogenous transcripts in mitochondria.  Since cytosolic expression of mitochondrial encoded subunits fails to result in functional incorporation into the ETC, this approach will allow the analysis of controlled disturbance of electron transport chain activity and its effect on synaptic plasticity and neural viability.

In parallel, I have begun work on a major project that aims to identify the role that Ncb5or, a novel oxidoreductase, plays in altered iron metabolism and dyshomeostasis in neurodegenerative diseases.  Diseases such as Friedreich's ataxia exhibit many of these same characteristics, including a 30% diabetes incidence amongst patients and significant defects in iron metabolism and iron-sulfur cluster processing, resulting in iron accumulation in mitochondria. Ncb5or has been shown to play a critical, albeit uncharacterized, role in iron metabolism/homeostasis in mice.  Global knockout mice rapidly develop lean diabetes and exhibit cognitive, behavioral, and neuromuscular junction defects at an early age, prior to the onset of diabetes.  Also, significant changes in electron transport chain complex levels accompany a drastic change in mitochondrial respiratory rate and oxygen consumption.  I am currently working with a brain-specific Ncb5or knock-out mouse that results in a functionally inactive form of Ncb5or in the brain. Preliminary data suggest that these mice exhibit the same defects seen with the global, non-diabetic knockout mice as well as other uncharacterized phenotypes. One significant benefit of the brain specific knockout model is that of lifespan. Global knockout mice rapidly develop diabetes and die at a relatively young age (20 weeks in males). It is critical to work with a model that will allow us to evaluate the neurological deficits that progress with age. Unfortunately, treatment for Friedreich's ataxia associated neurological deficits is limited to symptom maintenance and slowed disease progression, involving physical therapy sessions with low resistance training and gait training using visual cues.  While such methods have proved successful in temporarily improving quality of life and slowing disease progression, no therapy or target has been identified that can halt disease progression all together. Understanding the role of Ncb5or in iron processing and neurodegenerative diseases might help to identify pathways or processes that are potential targets for therapeutic intervention.

Last modified: Aug 17, 2015