Joseph Roche

Joseph Roche
Wayne State University | WSU · Health Care Sciences

BPT PhD

About

77
Publications
8,587
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805
Citations
Introduction
Research Area: Regenerative Muscle Biology and Pharmacology. Research Methods: In Vivo Neuromuscular Physiology, Histology, Protein Biochemistry, Gene Expression. Current Projects: Dosage adjusted exercise interventions to prevent muscle loss and/or regrow lost muscle.
Additional affiliations
July 2012 - January 2014
University of Maryland, Baltimore
Position
  • Professor (Assistant)
April 2011 - June 2012
University of Maryland, Baltimore
Position
  • Research Associate Faculty

Publications

Publications (77)
Article
Full-text available
Progressive resistance training (PRT), which involves performing muscle contractions against progressively greater external loads, can increase muscle mass and strength in healthy individuals and in patient populations. There is a need for precision rehabilitation tools to test the safety and effectiveness of PRT to maintain and/or restore muscle m...
Article
Full-text available
Physical activity (PA) is beneficial for the health and wellness of individuals and societies. During an infectious disease pandemic, such as the one caused by COVID-19, social distancing, quarantines, and lockdowns are used to reduce community spread of the disease. Unfortunately, such nonpharmacological interventions or physical risk mitigation m...
Article
Full-text available
Date Presented Accepted for AOTA INSPIRE 2021 but unable to be presented due to online event limitations Individuals with adult-onset muscular dystrophies do not die from the disease but have progressive loss of occupational performance (OP) and quality of life. There is no consistent pathway for referral and access to rehab services. OTs are under...
Article
Full-text available
μ-Crystallin, encoded by the CRYM gene, binds the thyroid hormones, T3 and T4. Because T3 and T4 are potent regulators of metabolism and gene expression, and CRYM levels in human skeletal muscle can vary widely, we investigated the effects of overexpression of Crym. We generated transgenic mice, Crym tg, that expressed Crym protein specifically in...
Article
Full-text available
Date Presented 03/28/20 Individuals with adult-onset muscular dystrophies do not die from the disease but have progressive loss of occupational performance (OP) and quality of life. There is no consistent pathway for referral and access to rehab services. OTs are underutilized, even though the greatest need is improvement in OP. The lack of guideli...
Article
Full-text available
As of April 20, 2020, over time, the COVID‐19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival...
Article
Introduction Dysferlin‐deficient murine muscle sustains severe damage after repeated eccentric contractions. Methods With a robotic dynamometer, we studied the response of dysferlin‐sufficient and ‐deficient mice to 12 weeks of concentrically‐ or eccentrically‐biased contractions. We also studied whether concentric contractions before or after ecc...
Article
The growing field of Regenerative Rehabilitation has great potential to improve clinical outcomes for individuals with disabilities. However, the science to elucidate the specific biological underpinnings of Regenerative Rehabilitation-based approaches is still in its infancy and critical questions regarding clinical translation and implementation...
Article
Full-text available
Introduction The aim of this study was to quantify the extent of donor-cell-derived myogenesis achieved by a novel surgical technique known as Minimally Invasive Muscle Embedding (MIME). Materials and Methods Through MIME, we implanted a single extensor digitorum longus muscle from donor mice (N = 2) that expressed a red fluorescent protein (RFP),...
Data
Table S1. DTZ versus VEH preinjury torque. Table S2. DTZ versus VEH immediate postinjury torque. Table S3. DTZ versus VEH day 3 postinjury torque. Table S4. H&E ‐ damaged fibers (% total). Table S5. IgG (+) and desmin (−) fibers (% total).
Article
Full-text available
B6.A‐Dysfprmd/GeneJ (BLAJ) mice model human limb‐girdle muscular dystrophy 2B (LGMD2B), which is linked to mutations in the dysferlin (DYSF) gene. We tested the hypothesis that, the calcium ion (Ca2+) channel blocker diltiazem (DTZ), reduces contraction‐induced skeletal muscle damage, in BLAJ mice. We randomly assigned mice (N = 12; 3–4 month old m...
Preprint
Full-text available
We found that diltiazem improved contractile torque before and immediately after forced eccentric contractions in dysferlin-deficient BLAJ mice, but did not reduce delayed-onset muscle damage that was observed at 3 days after eccentric contractions.
Article
Full-text available
The 6th International Symposium on Regenerative Rehabilitation, hosted by the Alliance for Regenerative Rehabilitation Research and Training (AR3T), included a preconference meeting of institutional representatives of the International Consortium of Regenerative Rehabilitation, keynote talks from distinguished scientists, platform and poster presen...
Preprint
Full-text available
We report that, labeling mouse muscle tissue, with mouse monoclonal antibodies specific to slow or fast myosin heavy chain (sMyHC and fMyHC, respectively), can lead to artefactual labeling of damaged muscle fibers, as hybrid fibers (sMyHC+ and fMyHC+). We demonstrate that such erroneous immunophenotyping of muscle may be avoided, by performing cola...
Article
Full-text available
Skeletal muscle possesses regenerative capacity due to tissue-resident, muscle-fiber-generating (myogenic) satellite cells (SCs), which can form new muscle fibers under the right conditions. Although SCs can be harvested from muscle tissue and cultured in vitro, the resulting myoblast cells are not very effective in promoting myogenesis when transp...
Article
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We performed a placebo-controlled pre-clinical study to determine if sodium 4-phenylbutyrate (4PB) can reduce contraction-induced myofiber damage in the mdx mouse model of Duchenne muscular dystrophy (DMD). At 72 h post-eccentric contractions, 4PB significantly increased contractile torque and reduced myofiber damage and macrophage infiltration. We...
Article
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Abstract Background: Studies of the pathogenic mechanisms underlying human myopathies and muscular dystrophies often require animal models, but models of some human diseases are not yet available. Methods to promote the engraftment and development of myogenic cells from individuals with such diseases in mice would accelerate such studies and also p...
Article
Mutations in the dysferlin gene (DYSF) lead to human muscular dystrophies known as dysferlinopathies. The dysferlin-deficient A/J mouse develops a mild myopathy after 6 months of age and, when younger, models the subclinical phase of the human disease. We subjected the tibialis anterior muscle of 3- to 4-month-old A/J mice to in vivo large-strain i...
Article
Introduction: We adopted a proteomics-based approach to gain insights into phenotypic differences between A/J and B10.SJL murine dysferlinopathy models. Methods: We optimized immunoblotting of dysferlin by preparing homogenates of the tibialis anterior (TA) muscle under several different conditions. We compared TA muscles of control, A/J, and B1...
Article
Full-text available
Oxidative stress is a critical disease modifier in the muscular dystrophies. Recently, we discovered a pathway by which mechanical stretch activates NADPH Oxidase 2 (Nox2) dependent ROS generation (X-ROS). Our work in dystrophic skeletal muscle revealed that X-ROS is excessive in dystrophin-deficient (mdx) skeletal muscle and contributes to muscle...
Article
Full-text available
Dysferlinopathies, most commonly limb girdle muscular dystrophy 2B and Miyoshi myopathy, are degenerative myopathies caused by mutations in the DYSF gene encoding the protein dysferlin. Studies of dysferlin have focused on its role in the repair of the sarcolemma of skeletal muscle, but dysferlin's association with calcium (Ca(2+)) signaling protei...
Article
Full-text available
Mutations in the dysferlin gene are the cause of Limb-girdle Muscular Dystrophy type 2B and Miyoshi Myopathy. The dysferlin protein has been implicated in sarcolemmal resealing, leading to the idea that the pathophysiology of dysferlin deficiencies is due to a deficit in membrane repair. Here, we show using two different approaches that fulfilling...
Data
Characterization of TgMyof. A/Assessment of myoferlin levels in subcellular fractionations. The distribution of myoferlin in TA muscles was examined by Western analysis of subcellular fractions prepared using SPEK muscle extract from WT and TgMyof mice. Equal volumes of each fraction (nucleus, cytosol, membrane, cytoskeleton) were analyzed and show...
Data
AAV vector for minidysferlin. A/Upper scheme: Scheme of the protein domain organization of the dysferlin protein with its 7 C2 (from C2A to C2G), Fer, Dysf and transmembrane domains. Middle scheme: Scheme of the minidysferlin used in this study. Lower scheme: Scheme of the rAAV construct for minidysferlin. B/Western Blot using Hamlet antibody was p...
Article
Full-text available
Mutations in the DYSF gene, encoding dysferlin, cause muscular dystrophies in man. We compared 4 dysferlinopathic mouse strains: SJL/J and B10.SJL-Dysf(im)/AwaJ (B10.SJL), and A/J and B6.A-Dysf(prmd)/GeneJ (B6.A/J). The former but not the latter two are overtly myopathic and weaker at 3 months of age. Following repetitive large-strain injury (LSI)...
Data
Full-text available
Figure S1. Data from multiple sets of B6.A/J mice. Due the high level of variability seen in B6.A/J animals, we performed physiological measurements on additional sets of animals. Data from 24 animals in 4 different sets are presented. Figure S2. Comparison of torque data between multiple sets of B6.A/J, and a single set of C57Bl/6J and A/J mice. W...
Article
Full-text available
Mutations in the DYSF gene that severely reduce the levels of the protein dysferlin are implicated in muscle-wasting syndromes known as dysferlinopathies. Although studies of its function in skeletal muscle have focused on its potential role in repairing the plasma membrane, dysferlin has also been found, albeit inconsistently, in the sarcoplasm of...
Article
Full-text available
Electroporation (EP) is used to transfect skeletal muscle fibers in vivo, but its effects on the structure and function of skeletal muscle tissue have not yet been documented in detail. We studied the changes in contractile function and histology after EP and the influence of the individual steps involved to determine the mechanism of recovery, the...
Article
Full-text available
Muscle strains are one of the most common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and physical exam alone, however the clinical presentation can vary greatly depending on the extent of injury, the patient's pain tolerance, etc. In patients with muscle injury or muscle disease, assessment of...
Conference Paper
Membrane tears in dysferlin deficient muscle fibers are the effects of a physiologic response to particular mechanic stress like lengthening contractions. Sarcolemmal membrane disruption can either lead to fiber necrosis or repair but little is known about the size and the kinetics of formation of the tears. To study this, we subjected dysferlin-de...
Article
Mutations in the gene DYSF, which codes for the protein dysferlin, underlie Miyoshi myopathy and limb-girdle muscular dystrophy 2B in humans and produce a slowly progressing skeletal muscle degenerative disease in mice. Dysferlin is a Ca(2+)-sensing, regulatory protein that is involved in membrane repair after injury. To assess the function of dysf...
Article
We studied the response of dysferlin-null and control skeletal muscle to large- and small-strain injuries to the ankle dorsiflexors in mice. We measured contractile torque and counted fibers retaining 10-kDa fluorescein dextran, necrotic fibers, macrophages, and fibers with central nuclei and expressing developmental myosin heavy chain to assess co...
Article
Full-text available
Obscurin is a large ( approximately 800-kDa), modular protein of striated muscle that concentrates around the M-bands and Z-disks of each sarcomere, where it is well positioned to sense contractile activity. Obscurin contains several signaling domains, including a rho-guanine nucleotide exchange factor (rhoGEF) domain and tandem pleckstrin homology...
Article
We used a gait analysis system (GAS) to measure the changes in locomotion parameters of adult Sprague-Dawley rats after neuromuscular injury, induced by repeated large-strain lengthening contractions of the dorsiflexors muscles. We developed a logistic regression model from test runs of control and permanently impaired (denervation of the dorsiflex...
Article
The protein, dysferlin, mediates sarcolemmal repair in vitro, implicating defective membrane repair in dysferlinopathies. To study the role of dysferlin in vivo, we assessed contractile function, sarcolemmal integrity, and myogenesis before and after injury from large-strain lengthening contractions in dysferlin-null and control mice. We report tha...
Article
Full-text available
Amount of drug actually reaching the target region in the lung following pulmonary inhalation is often estimated at less than 10% for older devices. Current particle and device engineering technologies have improved on this but still fail to recover the "wasted" fraction of the drug and deliver it deeper into the lungs, which is generally desirable...
Conference Paper
Full-text available
We describe an instrument that assesses two features of the gait of rats, spatiotemporal paw movement variables (SPMV) and ground reaction forces (GRF) in the vertical direction. The GRF and the SPMV variables are measured electrically by eight single axis load-cells that support two floor plates. We can derive four gait parameters from the SPMV an...