Biology subjects

Burns, K. A.

Publications and source records attributed to Burns, K. A..

3 recordsLinked to original sources

bioRxiv2025

Analysis of menstrual effluent uncovers endometriosis-specific cell populations and impaired cellular pathway processes

Endometriosis is a chronic gynecological disease affecting 1 in 10 reproductive-aged women and is characterized by the ectopic presence of endometrial tissue outside the uterus. The leading hypothesis for disease etiology is via the reflux of menstrual effluent (ME) into the peritoneal cavity. ME is a complex mixture of viable endometrial tissue, proteins, and immune cells which serve specialized functions during menstruation to support and repair the endometrium. We hypothesized shifts in the subpopulations of immune cells present during retrograde menstruation may alter the microenvironment of the peritoneal cavity leading to a favorable environment for uterine tissue attachment and survival of endometriotic lesions. Menstrual effluent collected on days 1 and 2 of menstruation identified from women with endometriosis distinct morphological features, increased subpopulations of aged neutrophils, increased anti-inflammatory macrophages, and overall impaired clearance pathways that hijack endometrial clearance likely contributing to the development and progression of endometriosis.

immunology↗

bioRxiv2023

The Role of MAP3K1 in the Development of the Female Reproductive Tract

Mitogen-Activated Protein 3 Kinase 1 (MAP3K1) is a dynamic signaling molecule with a plethora of cell-type specific functions, most of which are yet to be understood. Here we describe a role for MAP3K1 in the development of female reproductive tract (FRT). MAP3K1 kinase domain-deficient (Map3k1{Delta}KD) females exhibit imperforate vagina, labor failure, and infertility. These defects correspond to a shunted Mullerian duct (MD), the principle precursor of the FRT, in embryos, while they manifest as a contorted caudal vagina with abrogated vaginal-urogenital sinus fusion in neonates. In epithelial cells, MAP3K1 acts through JNK and ERK to activate WNT, yet in vivo MAP3K1 is crucial for WNT activity in mesenchyme associated with the caudal MD. Expression of Wnt7b is high in wild type, but low in Map3k1 knockout MD epithelium and MAP3K1-deficient keratinocytes. Correspondingly, conditioned media derived from MAP3K1-competent epithelial cells activate TCF/Lef-luciferase reporter in fibroblasts, suggesting that MAP3K1-induced factors released from epithelial cells trans-activate WNT signaling in fibroblasts. Our results reveal a temporal-spatial and paracrine MAP3K1-WNT crosstalk contributing to MD caudal elongation and FRT development. HighlightsO_LIMAP3K1 deficient female mice exhibit imperforate vagina and infertility C_LIO_LILoss of MAP3K1 kinase activity impedes Mullerian duct (MD) caudal elongation and fusion with urogenital sinus (UGS) in embryogenesis C_LIO_LIThe MAP3K1-MAPK pathway up-regulates WNT signaling in epithelial cells C_LIO_LIMAP3K1 deficiency down-regulates Wnt7b expression in the MD epithelium and prevents WNT activity in mesenchyme of the caudal MD C_LI

developmental biology↗

bioRxiv2021

Hyperconcentrated Mucus Unifies Submucosal Gland and Superficial Airway Dysfunction in Cystic Fibrosis

Cystic fibrosis (CF) is characterized by abnormal transepithelial ion transport. However, a description of CF lung disease pathophysiology unifying superficial epithelial and submucosal gland (SMG) dysfunctions has remained elusive. We hypothesized that biophysical abnormalities associated with CF mucus hyperconcentration provide a unifying mechanism. Studies of the anion secretion-inhibited pig airway CF model revealed elevated SMG mucus concentrations, osmotic pressures, and SMG mucus accumulation. Human airway studies revealed hyperconcentrated CF SMG mucus with raised osmotic pressures and cohesive forces predicted to limit SMG mucus secretion/release. Utilizing proline-rich protein 4 (PRR4) as a biomarker of SMG secretion, proteomics analyses of CF sputum revealed markedly lower PRR4 levels compared to healthy and bronchiectasis controls, consistent with a failure of CF SMGs to secrete mucus onto airway surfaces. Raised mucus osmotic/cohesive forces, reflecting mucus hyperconcentration, provide a unifying mechanism that describes disease-initiating mucus accumulation on airway surfaces and within SMGs of the CF lung.

pathology↗