- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Asthma and respiratory diseases
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Immune cells in cancer
- IL-33, ST2, and ILC Pathways
- Neonatal Respiratory Health Research
- Respiratory Support and Mechanisms
- Fibroblast Growth Factor Research
- Medical Imaging and Pathology Studies
- Occupational and environmental lung diseases
- Protein Tyrosine Phosphatases
- PI3K/AKT/mTOR signaling in cancer
- Lipid metabolism and biosynthesis
- Immune Response and Inflammation
- Congenital Diaphragmatic Hernia Studies
- Caveolin-1 and cellular processes
- Immune Cell Function and Interaction
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Liver Disease Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Pancreatitis Pathology and Treatment
University of California, San Francisco
2014-2025
Cardiovascular Institute Hospital
2016-2024
University of San Francisco
2024
University of California System
2007
University Hospital of Geneva
2001
Inserm
2001
SUNY Downstate Health Sciences University
2001
State University of New York
2001
The integrin receptor alphavbeta5 controls two independent forms of interactions the retinal pigment epithelium (RPE) with adjacent photoreceptor outer segments that are essential for vision. Alphavbeta5 localizes specifically to apical microvilli RPE and contributes adhesion maintains contacts intact at all times. Additionally, synchronizes diurnal bursts phagocytosis clear segment fragments (POS) shed in a circadian rhythm. Dependence on receptors suggests extracellular matrix ensheathing...
Milk fat globule epidermal growth factor 8 (Mfge8) is a soluble glycoprotein known to regulate inflammation and immunity by mediating apoptotic cell clearance. Since fibrosis can occur as result of exaggerated apoptosis inflammation, we set out investigate the hypothesis that Mfge8 might negatively tissue fibrosis. We report here does decrease severity in mouse model pulmonary fibrosis; however, it so not through effects on clearance, but binding targeting collagen for cellular uptake its...
Tumor cells secrete factors that modulate macrophage activation and polarization into M2 type tumor-associated macrophages, which promote tumor growth, progression, metastasis. The mechanisms mediate this are not clear. Macrophages phagocytic participate in the clearance of apoptotic cells, a process known as efferocytosis. Milk fat globule- EGF factor 8 (MFG-E8) is bridge protein facilitates efferocytosis associated with suppression proinflammatory responses. This study investigated...
Objective Intestinal fibrosis is considered an inevitable consequence of chronic IBD, leading to stricture formation and need for surgery. During the process fibrogenesis, extracellular matrix (ECM) components critically regulate function mesenchymal cells. We characterised composition ECM in fibrostenosing Crohn’s disease (CD) control tissues. Design Decellularised full-thickness intestinal tissue platforms were tested using three different protocols, phenotypes was explored by proteomics...
Abstract Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, mechanisms by which these processes develop interact within growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in progenitors results regionally restricted developmentally arrested microglia persist...
Efficient alveolar epithelial repair is crucial for the restoration of injured barrier in patients with acute lung injury (ALI) and respiratory distress syndrome (ARDS). We hypothesized that pulmonary edema fluid from ALI / ARDS would inhibit as measured an vitro wound-repair model using human epithelial-like cell line A549. In contrast to our initial hypothesis, increased by 33 ± 3% compared pooled plasma healthy donors (p < 0.01). By contrast, hydrostatic edema, had similar effects on...
Abstract Eosinophil recruitment and mucus hypersecretion are characteristic of asthmatic airway inflammation, but eosinophils have not been shown to induce mucin production. Because an epidermal growth factor receptor (EGFR) cascade induces MUC5AC in airways, because EGFR is up-regulated we examined the effect on production NCI-H292 cells (a human epithelial cell line that produces mucins). Eosinophils were isolated from peripheral blood allergic patients, their effects gene protein...
Biologically active interleukin (IL)-1β is present in the pulmonary edema fluid obtained from patients with acute lung injury and has been implicated as an important early mediator of nonpulmonary epithelial wound repair. Therefore, we tested hypothesis that IL-1β would enhance repair cultured monolayers rat alveolar type II cells. (20 ng/ml) increased rate vitro by 118 ± 11% compared serum-free medium control cells ( P < 0.01). induced cell spreading migration at edge but not...
Pretreatment with keratinocyte growth factor (KGF) ameliorates experimentally induced acute lung injury in rats. Although alveolar epithelial type II cell hyperplasia probably contributes, the mechanisms underlying KGF's protective effect remain incompletely described. Therefore, we tested hypothesis that KGF given to rats vivo would enhance repair vitro by nonproliferative mechanisms. After intratracheal instillation (48 h) of (5 mg/kg), cells were isolated for studies. KGF-treated had...
Apoptosis is a critical process in normal mammary gland development and the rapid clearance of apoptotic cells prevents tissue injury associated with release intracellular antigens from dying cells. Milk fat globule-EGF-factor 8 (Mfge8) milk glycoprotein that abundantly expressed epithelium has been shown to facilitate lymphocytes by splenic macrophages. We report mice disruption Mfge8 had until involution. However, abnormal remodeling was observed postlactation mutant mice. During early...
Airway obstruction is a hallmark of allergic asthma and caused primarily by airway smooth muscle (ASM) hypercontractility. inflammation leads to the release cytokines that enhance ASM contraction increasing ras homolog gene family, member A (RhoA) activity. The protective mechanisms prevent or attenuate increase in RhoA activity have not been well studied. Here, we report mice lacking encodes protein Milk Fat Globule-EGF factor 8 ( Mfge8 −/− ) develop exaggerated hyperresponsiveness...
Although aging represents the most important epidemiologic risk factor for fibrotic disease, reasons this are incompletely understood. Excess collagen deposition in tissues is sine qua non of tissue fibrosis and can be viewed as an imbalance between production degradation. Yet we still lack a detailed understanding changes that take place during development, maturation, extracellular matrix (ECM) dynamics. Resolution impaired aging, impairment may explain why age diseases, such idiopathic...
The small intestine has an underappreciated role as a lipid storage organ. Under conditions of high dietary fat intake, enterocytes can minimize the extent postprandial lipemia by storing newly absorbed in cytoplasmic droplets. Lipid droplets be subsequently mobilized for production chylomicrons. mechanisms that regulate this process are poorly understood. We report here milk protein Mfge8 regulates hydrolysis after interacting with αvβ3 and αvβ5 integrins. Mice deficient or integrins...
Abstract Accumulating evidence has implicated impaired extracellular matrix (ECM) clearance as a key factor in fibrotic disease. Despite decades of research elucidating the effectors ECM clearance, relatively little is understood regarding upstream regulation this process. Collagen most abundant constituent normal and mammalian tissues. Its catabolism occurs through proteolysis cell-mediated uptake collagen fragments for intracellular degradation. Given paucity information latter process,...