In the Peault Lab at the Orthopaedic Hospital Research Center, we investigate perivascular mesenchymal progenitor cells in human lipedema adipose tissue, which regulate adipogenesis, fibrosis, vascular remodeling, and tissue repair and may contribute directly to disease pathogenesis. Using fresh lipedema samples, we profile the distribution, phenotype, lineage potential, and function of these progenitors. Immunohistochemistry and quantitative imaging on frozen sections are used to analyze CD34, CD146, CD90, CD201, and CD31 expression relative to vascular and fibrotic regions. In parallel, fresh tissue is enzymatically digested to isolate stromal vascular fractions for flow cytometry and in vitro assays. Our analyses reveal a distinct progenitor landscape, with CD34-positive adventitial cells and CD146-positive pericytes occupying complementary vessel-associated niches. We also identify a rare CD201-positive population enriched around small vessels, suggesting altered niche retention and progenitor mobilization. Functionally, these cells show limited adipogenic differentiation, variable osteogenic potential, and unstable fibrogenic responses in vitro. These findings suggest dysregulated progenitor behavior may involve pathways distinct from classical MSC signaling and warrant further investigation.

Preterm labor (PTL) is a leading cause of neonatal morbidity and mortality. A leading cause of PTL is intrauterine infection or inflammation (IUI). Softening and shortening of cervix are essential prior to parturition but the changes have not been characterized well due to difficulty in obtaining human tissue. Unlike many animals, cervical anatomy in Rhesus macaque is very similar to humans. This study investigates the relationship between IUI and cervical remodeling using a Rhesus macaque model. Intrauterine inflammation was induced via intra-amniotic injection of live E. coli to simulate intrauterine infection in humans. Formalin-fixed cervical tissues embedded in paraffin were stained with H&E, Masson’s Trichrome, and Verhoeff Elastin to characterize microscopic anatomy and evaluate collagen and elastin staining. Two-photon microscopy was used to enable high-resolution visualization of collagen and elastin organization. Compared to controls, histological staining showed infiltration of neutrophils in the endocervix of E. coli-exposed animals and enlarged mucin-producing secretory cells. These results indicate that inflammation induces molecular and structural changes contributing to collagen and elastin structural remodeling of the cervix during PTL. These findings address a critical gap in understanding inflammation-associated cervical remodeling in a physiologically relevant model of preterm labor to inform future strategies for early detection and intervention.

TSC22D2 is a relatively uncharacterized protein, and its expression pattern and potential role in adipose tissue are not well understood. This project aims to characterize TSC22D2 across mouse tissues, define its localization within adipose tissue, and examine how its expression changes during adipocyte differentiation. To address these questions, immunofluorescence using primary and secondary antibodies with confocal microscopy will be used to determine the subcellular localization of TSC22D2. A tissue panel collected from 3-4 mice will be analyzed by western blot and qPCR to compare expression across multiple tissues. White adipose tissue will also be digested with collagenase and separated into stromal vascular fraction and adipocyte fractions to assess depot-specific and cell-type-specific expression by western blot and qPCR. In addition, stromal vascular fraction cells will be isolated, differentiated into adipocytes, and collected across a time course to evaluate changes in TSC22D2 expression during adipogenesis. Together, these experiments will provide a foundational characterization of TSC22D2 at the tissue, cellular, and subcellular levels. This work will help clarify whether TSC22D2 is enriched in specific adipose compartments or dynamically regulated during differentiation, providing a basis for future studies on its function in adipose biology.

Fragile X Mental Retardation Protein (FMRP) is a key regulator of cellular stress responses and lysosomal efficiency. Since a lack of FMRP would disrupt stress response pathways, we hypothesized that FMRP deficiency would increase the rate of senescence in both control and Doxorubicin-treated (Doxo) bone marrow-derived macrophages (BMDMs). To test this hypothesis, we compared wild-type (WT) and FMRP knockout (KO) BMDMs under control versus Doxo conditions to assess senescence-associated β-galactosidase (β-gal) staining. We imaged Day 6 Doxo samples and Day 7 control samples at 10x magnification in 3 distinct fields per condition. We counted total cells, partially β-gal positive cells (partial blue staining), and fully β-gal positive cells (complete blue staining) in each image. Statistical analysis was performed using Welch’s t-test. Doxo samples had increased β-gal staining overall which is consistent with the induction of senescence due to the nature of the treatment. Importantly, FMRP KO BMDMs showed greater β-gal staining than WT BMDMs. This effect was exaggerated with Doxo treatment. These findings suggest that loss of FMRP increases the rate of senescence in macrophages under both control and stress conditions (Doxo). Even though there are previous studies indicating that FMRP deficiency may actually increase lysosome activity, our results present a new perspective in which FMRP deficiency in the long term can also lead to senescence and chronic inflammation.