A5063809151- Phagocytosis and Immune Regulation
- Erythrocyte Function and Pathophysiology
- Chronic Myeloid Leukemia Treatments
- Protein Kinase Regulation and GTPase Signaling
- Synthesis and biological activity
- Synthesis of Tetrazole Derivatives
- Cell Adhesion Molecules Research
- Drug-Induced Hepatotoxicity and Protection
- Autophagy in Disease and Therapy
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- Signaling Pathways in Disease
- Drug Transport and Resistance Mechanisms
- Immune cells in cancer
- Pancreatitis Pathology and Treatment
- Immune Cell Function and Interaction
- COVID-19 Clinical Research Studies
- Pharmacogenetics and Drug Metabolism
- Cytokine Signaling Pathways and Interactions
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Nerve injury and regeneration
- Melanoma and MAPK Pathways
- Cellular Mechanics and Interactions
- Fungal Plant Pathogen Control
Rutgers, The State University of New Jersey
2016-2025
Rutgers New Jersey Medical School
2015-2024
University Hospital, Newark
2010-2023
Rutgers Cancer Institute of New Jersey
2018-2023
Ashwini Hospital
2014
Rutgers Health
2014
Newark Academy
2013
Milbank Memorial Fund
2010-2011
Kyoto University
2010
Utrecht University
2007
The immunogenicity of malignant cells has recently been acknowledged as a critical determinant efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology neoplastic cells. It is now clear that can succumb some anticancer therapies by undergoing peculiar form cell death characterized an increased...
The Crk adaptor proteins (Crk and CrkL) constitute an integral part of a network essential signal transduction pathways in humans other organisms that act as major convergence points tyrosine kinase signaling. integrate signals from wide variety sources, including growth factors, extracellular matrix molecules, bacterial pathogens, apoptotic cells. Mounting evidence indicates dysregulation is associated with human diseases, cancer susceptibility to pathogen infections. Recent structural work...
The extracellular matrix exerts a stringent control on the proliferation of normal cells, suggesting existence mitogenic signaling pathway activated by integrins, but not significantly growth factor receptors. Herein, we provide evidence that integrins cause significant and protracted activation Jun NH2-terminal kinase (JNK), while several factors more modest or no this enzyme. Integrin-mediated stimulation JNK required association focal adhesion (FAK) with Src p130CAS, phosphorylation...
Efficient phagocytosis of apoptotic cells is crucial for many cellular processes. One earliest signals to the phagocyte expression phosphatidylserine (PS) on outer surface cell that provides a potent 'eat-me' signal. Recognition PS occurs either directly, via receptor (PS-R), or indirectly alphavbeta5(3) integrin Mer-family tyrosine kinases through opsonizing proteins milk fat globule-EGF factor 8 protein (MFG-E8), growth arrest specific factor-6 (Gas6), respectively. Because Mer and...
The genome of avian sarcoma virus CT10 encodes a fusion protein in which viral Gag sequences are fused to cellular Crk containing primarily Src homology 2 (SH2) and 3 (SH3) domains. Transformation chicken embryo fibroblasts (CEF) with the Gag-Crk results elevation tyrosine phosphorylation on specific proteins molecular weights 130,000, 110,000, 70,000 (p130, p110, p70, respectively), an event has been correlated cell transformation. In this study, we have identified 70-kDa...
The small GTPase Rho acts on two effectors, ROCK and mDia1, induces stress fibers focal adhesions. However, how mDia1 individually regulate signals dynamics of these structures remains unknown. We stimulated serum-starved Swiss 3T3 fibroblasts with LPA compared the effects C3 exoenzyme, a inhibitor, those Y-27632, inhibitor. Y-27632 treatment suppressed LPA-induced formation adhesions as did exoenzyme but induced membrane ruffles complexes, which were absent in exoenzyme-treated cells. This...
Transglutaminase 2 (TG2), a protein cross-linking enzyme with many additional biological functions, acts as coreceptor for integrin beta(3). We have previously shown that TG2(-/-) mice develop an age-dependent autoimmunity due to defective in vivo clearance of apoptotic cells. Here we report TG2 on the cell surface and guanine nucleotide-bound form promotes phagocytosis. Besides being binding partner beta(3), receptor known mediate uptake cells via activating Rac1, also show binds MFG-E8...
Inflammation resolution counterbalances excessive inflammation and restores tissue homeostasis after injury. Failure of contributes to the pathology numerous chronic inflammatory diseases. Resolution is mediated by endogenous specialized proresolving mediators (SPMs), which are derived from long-chain fatty acids lipoxygenase (LOX) enzymes. 5-LOX plays a critical role in biosynthesis two classes SPMs: lipoxins resolvins. Cytoplasmic localization nonphosphorylated form essential for SPM...
Abstract Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K–dependent endogenous ligands, Protein S (ProS), growth arrest–specific factor 6 (Gas6), act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). receptors overexpressed in a vast array tumor types, whereby the level expression correlates with grade emergence chemo- radioresistance targeted therapeutics, but...
Abstract Tyro3, Axl, and Mertk (TAM) represent a family of homologous tyrosine kinase receptors known for their functional role in phosphatidylserine (PS)-dependent clearance apoptotic cells also immune modulatory functions the resolution inflammation. Previous studies our laboratory have shown that Gas6/PS-mediated activation TAM on tumor leads to subsequent upregulation PD-L1, defining putative PS→TAM receptor→PD-L1 inhibitory signaling axis cancer microenvironment may promote tolerance....
Despite the promising clinical benefit of targeted and immune checkpoint blocking therapeutics, current strategies have limited success in breast cancer, indicating that additional inhibitory pathways are required to complement existing therapeutics. TAM receptors (Tyro-3, Axl, Mertk) often correlated with poor prognosis because their capacities sustain an immunosuppressive environment. Here, we ablate Axl on tumor cells using CRISPR/Cas9 gene editing, by targeting Mertk microenvironment...
Abstract The etiology of ulcerative colitis is poorly understood and likely to involve perturbation the complex interactions between mucosal immune system commensal bacteria gut, with cytokines acting as important cross-regulators. Here we use IFN receptor-deficient mice in a dextran sulfate sodium (DSS) model acute intestinal injury study contributions type I III interferons (IFN) initiation, progression resolution colitis. We find that lacking both types receptors exhibit enhanced barrier...
In viable healthy cells, membrane phospholipids are asymmetrically distributed across the lipid bilayer, whereby anionic phospholipid phosphatidylserine is virtually all on inner leaflet of plasma membrane. During apoptosis, asymmetry collapses and PS externalized to external where it serves as an "eat-me" signal for efferocytosis, process dying cells engulfed degraded by phagocytes. also activated tumor endothelial stromal cancer in microenvironment reflecting a pathophysiological state...
Nerve growth factor (NGF) and epidermal (EGF) elicit contrasting actions on PC12 pheochromocytoma cells; NGF causes neuronal differentiation, EGF induces proliferation. However, ectopic expression of the Src homology 2 (SH2) SH3-containing oncogenic adaptor protein v-Crk in cells results EGF-inducible differentiation (Hempstead, B. L., Birge, R. B., Fajardo, J. E., Glassman, R., Mahadeo, D., Kraemer, Hanafusa, H.(1994) Mol. Cell. Biol. 14, 1964-1971). Here we show that complexes with both...