February 2026 Seminar Presenters

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common dystrophy and affects about 1 in 8500 people globally. In FSHD patients, epigenetic dysregulation leads to aberrant expression of the transcription factor DUX4 in skeletal muscle. DUX4 is a pioneer transcription factor with many downstream targets, and although the exact mechanism of FSHD muscle pathology is still unknown, it is the area of active research and several promising therapeutics directed towards the expression of DUX4 are in clinical trial. FSHD biomarker characterization remains a high priority to evaluate therapeutic responses. Our laboratory is investigating the protein SLC34A2 as a potential FSHD biomarker. As a downstream target of DUX4, SLC34A2 is not typically expressed in healthy skeletal muscle, but its protein is increased significantly in FSHD muscle and cell lysates, making it a potential readout of FSHD disease progression. SLC34A2 encodes a sodium-phosphate co-transporter expressed in lung, kidney, and gut epithelia, but not in mature muscles. Previously, we have shown that SLC34A2 antibodies co-stain FSHD muscle biopsies, FSHD cultured myotubes, and our model of FSHD xenografts, where SLC34A2 is present in about 1%-2% of FSHD-affected fibers (Mueller et al., Exp. Neurol. 320: 113011, 2019). Our research shows that SLC34A2 mRNA and protein are significantly increased in maturing FSHD myotube cultures compared to controls. These levels decrease when myotubes are exposed to putative FSHD therapeutics such as p38 kinase inhibitors and AAV targeting DUX4 transcripts. Additionally, we can label SLC34A2-positive FSHD fibers in xenografts in-situ with an antibody specific to the exposed extracellular domain of SLC34A2 tagged with IR-647. This opens the prospect of tracking disease progression and the efficacy of different experimental therapies for FSHD in the same individuals over time, without the need for muscle biopsies. Preliminary data also shows when expressed in WT muscles, SLC34A2 affects myofiber health and may contribute to FSHD pathogenesis. 

 

Relevant Publications

• Bloch, R.J., et al., The recent clinical trial of losmapimod for the treatment of facioscapulohumeral muscular dystrophy. Neuromuscular Disorders, 2025. 52: p. 105422. https://pubmed.ncbi.nlm.nih.gov/40580827/

 

Title: Investigating the role of allergic airway inflammation in host responses to SARS-CoV-2 and influenza A virus

Although asthma is a risk factor for developing serious complications after infection with many respiratory viruses, epidemiological studies have shown that asthma protects individuals from severe COVID-19. We aim to understand the mechanism by which allergic asthma results in differential outcomes during respiratory infection with different viruses using a house-dust-mite (HDM)-induced allergic asthma mouse model. The HDM-treated mice, which exhibit allergic airway inflammation, were challenged along with either SARS-CoV-2 or H1N1 influenza A virus (IAV). After IAV challenge, the HDM-treated mice had increased weight loss and mortality as compared to the control mice. Conversely, after SARS-CoV-2 challenge, the HDM-treated mice had decreased weight loss compared to controls and were completely protected from mortality. To investigate the mechanism behind these differential disease outcomes, we began exploring various aspects of the allergic asthma milieu. Using flow cytometry to determine which immune cell populations are important to the protection seen after SARS-CoV-2 challenge, we identified eosinophils as a likely candidate. Specifically, we found that the percentage of eosinophils in the lungs of mice infected with SARS-CoV-2 was significantly higher in the HDM-treated group as compared to controls. Additionally, through further eosinophil phenotyping, we identified differential regulation of PDL1 expression between the two groups, such that although expression of PDL1 on eosinophils is higher at baseline in the control mice, eosinophils from the HDM-treated mice have significantly higher PDL1 expression than those from control mice after infection. Similar experiments with IAV challenge are ongoing to establish differences in eosinophil presence and phenotype as compared to the results from SARS-CoV-2 challenge. Additionally, we are utilizing mice with conditional eosinophil depletion to establish the overall role of eosinophils in disease outcomes following HDM treatment and virus challenge. Understanding the varied host responses to viral infection in asthmatics could lead to better therapeutics for these diseases.

Title: Measurement Model of Nursing Home Organizational Factors

Background:

Nursing home (NH) organizational characteristics such (e.g. staffing, profit status) are important contributors to the quality of care delivered to nursing home residents. Guided by Campbell’s Systems Based Model for Assessing Care, this study tested a measurement model of NH organizational characteristics. The hypothesized measurement model specified two latent factors: Facility Resources (profit status, size, percent Medicaid) and Care Delivery Resources (RN, LPN, CNA staffing).

Methods:

This cross-sectional secondary data analysis included 55 NH communities in Maryland and Pennsylvania using data from the Evidence Integration Triangle for Behavioral and Psychological Symptoms of Dementia (EIT-4-BPSD) study merged with data from LTCFocus. Structural equation modeling using Mplus was used to test the model. Fit statistics included χ² /df, Tucker Lewis Index (TLI), and root mean square error of approximation (RMSEA).

Results:

The model demonstrated excellent fit (χ² /df = 0.798, TLI = 1.00, RMSEA = 0.000). CNA staffing was a significant indicator for the Care Delivery Resource factor (β = 0.565, p = 0.008), and percent Medicaid (β = 0.950, p < 0.001) and profit status (β = 0.485, p < 0.001) were significant indicators of the Facility Resource factor.

Conclusion and Implications:

This study provides empirical support for a theoretically based measurement model of NH organizational factors. Future research should explore the impact of NH organizational factors on resident outcomes. Findings may also inform NH operating decisions and regulatory policy aimed at strengthening infrastructure to support quality care.

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Relevant Publications

• https://www.jamda.com/article/S1525-8610(24)00316-5/abstract
• https://pmc.ncbi.nlm.nih.gov/articles/PMC12354327/