Biology subjects

Chen, A. M.

Publications and source records attributed to Chen, A. M..

3 recordsLinked to original sources

bioRxiv2026

SIRT5 acts in the tumor microenvironment via endothelial cell metabolism to support breast cancer growth

Triple-negative breast cancer (TNBC) is characterized by aggressive progression and poor prognosis, partly due to abnormal angiogenesis. While the metabolic reprogramming of tumor cells is well characterized, the metabolic regulation of tumor-associated endothelial cells (ECs) remains unclear. Here, we identified the mitochondrial deacylase SIRT5, which has established tumor-promoting roles in TNBC cells, as a key regulator of endothelial metabolic homeostasis and tumor angiogenesis. SIRT5-deficient host mice showed significant defects in supporting the growth of orthotopic SIRT5-proficient mammary tumor transplants, and the resulting neoplasms showed defects in tumor vascularization. In a 3D microfluidic vessel-on-chip model, SIRT5 loss compromised vascular barrier integrity and EC sprouting. Mechanistically, SIRT5-deficient ECs exhibited diminished mitochondrial respiratory capacity but apparently normal glycolysis. SIRT5 loss also caused increased mitochondrial reactive oxygen species levels, and a mitochondrial antioxidant rescued the endothelial cell defects following SIRT5 loss, indicating that SIRT5-mediated mitochondrial redox homeostasis in the tumor microenvironment is necessary to maintain vascular function. Orthotopic co-transplantation of TNBC and EC cells with or without SIRT5 knockdown demonstrated that endothelial SIRT5 promotes increased tumor growth in vivo. These results suggest that targeting SIRT5 offers a potential therapeutic strategy to disrupt tumor angiogenesis and suppress TNBC progression by targeting the metabolic vulnerabilities of the tumor endothelium.

cancer biology↗

bioRxiv2025

Murine gut microbiota dysbiosis via enteric infection modulates the foreign body response to a distal biomaterial implant

The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response (FBR) and fibrosis around medical implants is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via enterotoxigenic Bacteroides fragilis (ETBF) infection and implanted the synthetic polymer polycaprolactone (PCL) into a distal muscle injury. ETBF infection in mice led to increased neutrophil and {gamma}{delta} T cell infiltration into the PCL implant site. ETBF infection alone promoted systemic inflammation and increased levels of neutrophils in the blood, spleen, and bone marrow. At the PCL implant site, we found significant changes in the transcriptome of sorted fibroblasts but did not observe gross ETBF- induced differences in the fibrosis levels after 6 weeks. These results demonstrate the ability of the gut microbiota to mediate long-distance effects such as immune and stromal responses to a distal biomaterial implant. Significance StatementThe foreign body response to implants leads to chronic inflammation and fibrosis that can be highly variable in the general patient population. Here, we demonstrate that gut dysbiosis via enteric infection promoted systemic inflammation and increased immune cell recruitment to an anatomically distant implant site. These results implicate the gut microbiota as a potential source of variability in the clinical biomaterial response and illustrate that the local tissue environment can be influenced by host factors that modulate systemic interactions.

bioengineering↗

bioRxiv2020

Comparison of porcine corneal decellularization methods and importance of preserving corneal limbus through decellularization

BackgroundThe aim of this study is to compare the three previously applied, conventional porcine corneal decellularization methods and to demonstrate the importance of preserving the corneal limbus through decellularization. MethodsFresh, wild-type (with or without) limbus porcine corneas were decellularized using three different methods, including (i) sodium dodecyl sulfate (SDS), (ii) hypertonic saline (HS), and (iii) N2 gas (NG). Post-treatment evaluation was carried out using histological, residual nuclear material, and ultrastructural analyses. Glycerol was used to help reduce the adverse effects of decellularization. The corneas were preserved for two weeks in cornea storage medium. ResultsAll three decellularization methods reduced the number of keratocytes at different rates in the stromal tissue. However, all methods, except SDS, resulted in the retention of large numbers of cells and cell fragments. The SDS method (0.1% SDS, 48h) resulted in almost 100% decellularization in corneas without limbus. Low decellularization capacity of the NG method (<50%) could make it unfavorable. Although HS method had a more balanced damage-decellularization ratio, its decellularization capacity was lower than SDS method. Preservation of the corneoscleral limbus could partially prevent structural damage and edema, but it would reduce the decellularization capacity. ConclusionOur results suggest that SDS is a very powerful decellularization method, but it damages the cornea irreversibly. Preserving the corneoscleral limbus reduces the efficiency of decellularization, but also reduces the damage.

bioengineering↗