Browsing by Author "Wilson, Christopher"

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    Carboxyl-terminal modulator protein (CTMP) deficiency mitigates denervation-induced skeletal muscle atrophy
    (Elsevier, 2023-02) Wang, Junmei; Tierney, Lydia; Wilson, Christopher; Phillips, Victoria; Goldman, Lillian; Mumaw, Christen; Muang, En; Walker, Chandler L.; Biomedical and Applied Sciences, School of Dentistry
    Denervated skeletal muscles show decreased Akt activity and phosphorylation, resulting in atrophy. Akt inhibits downstream transcription of atrophy-associated ubiquitin ligases like muscle ring-finger protein 1 (MuRF-1). In addition, reduced Akt signaling contributes to aberrant protein synthesis in muscles. In ALS mice, we recently found that carboxyl-terminator modulator protein (CTMP) expression is increased and correlated with reduced Akt signaling in atrophic skeletal muscle. CTMP has also been implicated in promoting muscle degeneration and catabolism in an in vitro muscle atrophy model. The present study examined whether sciatic nerve injury (SNI) stimulated CTMP expression in denervated skeletal muscle during muscle atrophy. We hypothesized that CTMP deficiency would reduce neurogenic atrophy and reverse Akt signaling downregulation. Compared to the unaffected contralateral muscle, wild-type (WT) gastrocnemius muscle had a significant increase in CTMP (p < 0.05). Furthermore, denervated CTMP knockout (CTMP-KO) gastrocnemius weighed more than WT muscle (p < 0.05). Denervated CTMP-KO gastrocnemius also showed higher Akt and downstream glycogen synthase kinase 3β (GSK3β) phosphorylation compared to WT muscle (p < 0.05) as well as ribosomal proteins S6 and 4E-BP1 phosphorylation (p < 0.001 and p < 0.05, respectively). Moreover, CTMP-KO mice showed significantly lower levels of E3 ubiquitin ligase MuRF-1 and myostatin than WT muscle (p < 0.05). Our findings suggest that CTMP is essential to muscle atrophy after denervation and it may act by reducing Akt signaling, protein synthesis, and increasing myocellular catabolism.
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    Institutional review of the management of type II odontoid fractures: associations and outcomes with fibrous union
    (AANS, 2021-04) Wilson, Christopher; Hoyos, Mariana; Huh, Andrew; Priddy, Blake; Avila, Stephen; Mendenhall, Stephen; Anokwute, Miracle C.; Eckert, George J.; Stockwell, David W.; Neurological Surgery, School of Medicine
    OBJECTIVE Type II odontoid fractures may be managed operatively or nonoperatively. If managed with bracing, bony union may never occur despite stability. This phenomenon is termed fibrous union. The authors aimed to determine associations with stable fibrous union and compare the morbidity of patients managed operatively and nonoperatively. METHODS The authors performed a retrospective review of their spine trauma database for adults with type II odontoid fractures between 2015 and 2019. Two-sample t-tests and Fisher’s exact tests identified associations with follow-up stability and were used to compare operative and nonoperative outcomes. Sensitivity, specificity, and predictive values were calculated to validate initial stable upright cervical radiographs related to follow-up stability. RESULTS Among 88 patients, 10% received upfront surgical fixation, and 90% were managed nonoperatively, of whom 22% had fracture instability on follow-up. Associations with instability after nonoperative management include myelopathy (OR 0.04, 95% CI 0.0–0.92), cerebrovascular disease (OR 0.23, 95% CI 0.06–1.0), and dens displacement ≥ 2 mm (OR 0.29, 95% CI 0.07–1.0). Advanced age was not associated with follow-up instability. Initial stability on upright radiographs was associated with stability on follow-up (OR 4.29, 95% CI 1.0–18) with excellent sensitivity and positive predictive value (sensitivity 89%, specificity 35%, positive predictive value 83%, and negative predictive value 46%). The overall complication rate and respiratory failure requiring ventilation on individual complication analysis were more common in operatively managed patients (33% vs 3%, respectively; p = 0.007), even though they were generally younger and healthier than those managed nonoperatively. Operative or nonoperative management conferred no difference in length of hospital or ICU stay, discharge disposition, or mortality. CONCLUSIONS The authors delineate the validity of upright cervical radiographs on presentation in association with follow-up stability in type II odontoid fractures. In their experience, factors associated with instability included cervical myelopathy, cerebrovascular disease, and fracture displacement but not increased age. Operatively managed patients had higher complication rates than those managed without surgery. Fibrous union, which can occur with nonoperative management, provided adequate stability.
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    Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma
    (Springer Nature, 2024) Wang, Justin Z.; Patil, Vikas; Landry, Alexander P.; Gui, Chloe; Ajisebutu, Andrew; Liu, Jeff; Saarela, Olli; Pugh, Stephanie L.; Won, Minhee; Patel, Zeel; Yakubov, Rebeca; Kaloti, Ramneet; Wilson, Christopher; Cohen-Gadol, Aaron; Zaazoue, Mohamed A.; Tabatabai, Ghazaleh; Tatagiba, Marcos; Behling, Felix; Almiron Bonnin, Damian A.; Holland, Eric C.; Kruser, Tim J.; Barnholtz-Sloan, Jill S.; Sloan, Andrew E.; Horbinski, Craig; Chotai, Silky; Chambless, Lola B.; Gao, Andrew; Rebchuk, Alexander D.; Makarenko, Serge; Yip, Stephen; Sahm, Felix; Maas, Sybren L. N.; Tsang, Derek S.; International Consortium on Meningiomas (ICOM); Rogers, C. Leland; Aldape, Kenneth; Nassiri, Farshad; Zadeh, Gelareh; Neurological Surgery, School of Medicine
    Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.