Erik Rader, PhD, BS

Research Assistant Professor

Organization:

West Virginia University School of Medicine

Department:

Orthopaedics

Classification:

Faculty

• BS, University of Michigan
• PhD, University of Michigan

Research Interests

I am a Research Assistant Professor with a focus on the biomechanics, molecular signaling, and morphology underlying musculoskeletal degeneration. My present focus is characterizing and developing novel therapeutic approaches regarding musculoskeletal deterioration during prosthetic joint infection following total joint replacement – a leading complication in orthopaedics. The work will entail delineating inflammatory signaling in tissue damage. To this end, my lab assesses joint/muscle performance, tissue/cellular morphology, protein biochemistry, and gene expression.  The findings of this line of research will provide the foundation for improving orthopaedic surgical outcomes.

Contributions to Science

1. Inflammation and Skeletal Muscle Maladaptation/Adaptation with Physical Activity and Aging: Elevated baseline levels of inflammation and oxidative stress are prevalent across tissues with aging in a phenomenon referred to as inflammaging. In the context of skeletal muscle, this is accompanied by decreased strength and compromised recovery following physical activity. Over several studies in a preclinical rat model, we tested the working hypothesis that less frequent repeated exposure to muscle contractions would improve the basal microenvironment and induce adaptation at old age. For instance, results from one study demonstrated that lowering exposure volume by decreasing the number of sessions per week restored baseline oxidative stress and muscle performance (in terms of muscle quality exclusively following reduced training frequency) to young levels (Rader, et al., 2016). This work established muscular activity as an influential intervention in the reversal of age-related inflammaging and skeletal muscle deficits. More recently, we demonstrated that a well regulated inflammatory response coincides with efficacious muscle adaptation in slow aging Snell dwarf mice (Rader et al., 2022 and 2024).

2. Biomechanics of Muscle Fibers Following Cleft Palate: Inability to close the soft palate against the back of the throat, velopharyngeal incompetence, occurs in 20% of patients who undergo cleft palate repair. Fiber type distribution may be a contributing factor underlying distinct outcomes. By evaluating the mechanical properties of single permeabilized muscle fibers, we tested the hypothesis that repair of the cleft palate, in most cases, induce an adaptive shift to a greater distribution of type 1 fibers that are resistant to muscle injury. Results from our work confirmed that repair induced a shift from a predominantly type 2 fibers to a distribution in which 80% of muscle fibers were type 1. This was accompanied by a twofold improvement in resistance to damage from lengthening contraction activity and subsequent inflammatory response. This line of research established such an adaptation as a potential process in preventing elopharyngeal incompetence and rather ensuring proper soft palate function (Rader et al., 2007 and Rader et al., 2008).

3. Extracellular/Intracellular Signaling and Skeletal Muscle Pathology: An aspect of my research has focused on characterizing signaling at the plasma membrane. For example, I have investigated the dystrophin-glycoprotein complex - a complex with dystroglycan as the key transmembrane protein linking the extracellular matrix to the cytoskeleton. This complex provides stability and signal transduction (Rader et al., 2016; Hord et al., 2026). When disrupted as in the case of many forms of muscular dystrophy, susceptibility to contraction-induced injury and muscle inflammation/degeneration are heightened. Early studies were unable to distinguish whether this propensity to injury was a primary effect of complex disruption or a secondary consequence of degeneration. Utilizing an inducible dystroglycan knockout mouse, we demonstrated that the susceptibility to contraction-induced injury increased prior to changes in sarcolemma fragility, excitation-contraction uncoupling, and necrosis (Kobayashi et al., 2008). A decrease in passive tension and titin immunofluorescence suggested mechanical disruption as an influential mechanism. Testing of isolated muscle ex vivo in various buffer conditions was instrumental in this study. Other work explored the role of the dystrophin-glycoprotein complex in interactions with neuronal nitric oxide synthase, dysferlin, and creatine kinase (Rader et al., 2016). Overall, this body of research established the nuance of this complex and dystroglycan, in particular, in establishing mechanical and biochemical signaling between the internal and external environment of muscle fibers - an essential mechanism for transmission across musculoskeletal tissues.

Selected Publications

1. Hord JM, Turk R, Kusano H, Rader EP, Burns S, Gastel Z, Prouty SJ, Yu L, Burden SJ, Campbell KP. Cytoplasmic region of beta-dystroglycan is essential for postsynaptic maturation and neuromuscular function in mice. Proc Natl Acad Sci U S A. 2026 Jun 9;123(23):e2600931123. PubMed PMID: 42234522.

2. Rader EP, McKinstry KA, Baker BA. Transcriptional and morphological responses following distinct muscle contraction protocols for Snell dwarf (Pit1(dw/dw)) mice. Physiol Rep. 2024 Sep;12(17):e70027. PubMed Central PMCID: PMC11371489.

3. Rader EP, Naimo MA, Ensey J, Baker BA. Improved impedance to maladaptation and enhanced VCAM-1 upregulation with resistance-type training in the long-lived Snell dwarf (Pit1(dw/dw)) mouse. Aging (Albany NY). 2022 Feb 3;14(3):1157-1185. PubMed Central PMCID: PMC8876912.

4. Rader EP, Baker BA. Elevated muscle mass accompanied by transcriptional and nuclear alterations several months following cessation of resistance-type training in rats. Physiol Rep. 2022 Oct;10(20):e15476. PubMed Central PMCID: PMC9579736.

5. Rader EP, Baker BA. Age-dependent stress response DNA demethylation and gene upregulation accompany nuclear and skeletal muscle remodeling following acute resistance-type exercise in rats. Facets (Ott). 2020 Jun 22;5(1):455-473. PubMed Central PMCID: PMC7413608.

6. Rader EP, Naimo MA, Layner KN, Triscuit AM, Chetlin RD, Ensey J, Baker BA. Enhancement of Skeletal Muscle in Aged Rats Following High-Intensity Stretch-Shortening Contraction Training. Rejuvenation Res. 2017 Apr;20(2):93-102. PubMed Central PMCID: PMC9206483.

7. Rader EP, Turk R, Willer T, Beltrán D, Inamori K, Peterson TA, Engle J, Prouty S, Matsumura K, Saito F, Anderson ME, Campbell KP. Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle. Proc Natl Acad Sci U S A. 2016 Sep 27;113(39):10992-7. PubMed Central PMCID: PMC5047148.

8. Kobayashi YM, Rader EP, Crawford RW, Iyengar NK, Thedens DR, Faulkner JA, Parikh SV, Weiss RM, Chamberlain JS, Moore SA, Campbell KP. Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature. 2008 Nov 27;456(7221):511-5. PubMed Central PMCID: PMC2588643.

9. Rader EP, Cederna PS, McClellan WT, Caterson SA, Panter KE, Yu D, Buchman SR, Larkin LM, Faulkner JA, Weinzweig J. Effect of cleft palate repair on the susceptibility to contraction-induced injury of single permeabilized muscle fibers from congenitally-clefted goat palates. Cleft Palate Craniofac J. 2008 Mar;45(2):113-20. PubMed Central PMCID: PMC2754268.

10. Rader EP, Cederna PS, Weinzweig J, Panter KE, Yu D, Buchman SR, Larkin LM, Faulkner JA. Contraction-induced injury to single permeabilized muscle fibers from normal and congenitally-clefted goat palates. Cleft Palate Craniofac J. 2007 Mar;44(2):216-22. PubMed Central PMCID: PMC2754850.