- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Hippo pathway signaling and YAP/TAZ
- Cellular Mechanics and Interactions
- Endoplasmic Reticulum Stress and Disease
- Connexins and lens biology
- Trace Elements in Health
- Ubiquitin and proteasome pathways
- Flavonoids in Medical Research
- Cellular transport and secretion
- Cancer-related Molecular Pathways
- Coenzyme Q10 studies and effects
- Advanced Glycation End Products research
- NF-κB Signaling Pathways
- Salmonella and Campylobacter epidemiology
- RNA regulation and disease
- Autophagy in Disease and Therapy
- Biological Activity of Diterpenoids and Biflavonoids
- Protease and Inhibitor Mechanisms
- Pancreatic function and diabetes
- Medicinal Plant Pharmacodynamics Research
- Microtubule and mitosis dynamics
- TGF-β signaling in diseases
- interferon and immune responses
- Protein Kinase Regulation and GTPase Signaling
University of Toledo
2014-2024
University of Michigan
2020-2024
U-M Rogel Cancer Center
2020
Indian Institute of Science Bangalore
2015
ABSTRACT One of the hallmarks cancer is ability tumor cells to invade surrounding tissues and metastasize. During metastasis, degrade extracellular matrix, which acts as a physical barrier, by developing specialized actin-rich membrane protrusion structures called invadopodia. The formation invadopodia regulated Rho GTPases, family proteins that regulates actin cytoskeleton. Here, we describe novel role for RhoG in regulation disassembly human breast cells. Our results show Rac1 have...
Circular dorsal ruffles (CDRs) are actin-rich structures that form on the surface of many mammalian cells in response to growth factor stimulation. CDRs represent a unique type structure forms transiently and only once upon The formation involves drastic rearrangement cytoskeleton, which is regulated by Rho family GTPases. So far, Rac1 has been consistently associated with CDR formation, whereas role other GTPases this process either lacking or inconclusive. Here we show RhoG its exchange...
The canonical Scribble polarity complex is implicated in regulation of epithelial junctions and apical polarity. Here, we show that SGEF, a RhoG-specific GEF, forms ternary with Dlg1, two members the complex. SGEF targets to Scribble-dependent fashion functions actomyosin-based contractility barrier function at tight as well E-cadherin-mediated formation adherens junctions. Surprisingly, does not control establishment However, 3D cysts, regulates single open lumen. Interestingly, SGEF's...
SGEF, a RhoG specific GEF, can form ternary complex with the Scribble polarity proteins and Dlg1, which regulates formation maintenance of adherens junctions barrier function epithelial cells. Notably, silencing SGEF results in dramatic downregulation both E-cadherin ZO-1 protein levels. However, molecular mechanisms involved regulation this pathway are not known. Here, we describe novel signaling governed by Scribble/SGEF/Dlg1 complex. Our show that three members required to maintain...
The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with cancer, suggesting that L may play additional roles in tumor suppression. Here, we demonstrate role as suppressor androgen receptor (AR) signaling, cell migration matrix metalloproteinase activity. Using mutants, show its nucleolytic...
The Unfolded Protein Response (UPR) plays a key role in the adaptive response to loss of protein homeostasis within endoplasmic reticulum (ER). UPR has an function homeostasis, however, sustained activation due hypoxia, nutrient deprivation, and increased demand for synthesis, alters program such that additional perturbation ER activates pro-apoptotic program. Since ubiquitination followed by proteasomal degradation misfolded proteins is central mechanism restoration inhibitors this pathway...
Salmonella hijack host machinery in order to invade cells and establish infection. While considerable work has described the role of proteins invasion, much less is known regarding how natural variation these invasion-associated affects pathogenesis. Here we leveraged a candidate cellular GWAS screen identify genetic ARHGEF26 ( Rho Guanine Nucleotide Exchange Factor 26 ) gene that renders lymphoblastoid susceptible Typhi Typhimurium invasion. Experimental follow-up redefined ARHGEF26’s...
Abstract Focal adhesions (FA) are a complex network of proteins that allow the cell to form physical contacts with extracellular matrix (ECM). FA assemble and disassemble in dynamic process, orchestrated by variety cellular components. However, underlying mechanisms regulate adhesion turnover remain poorly understood. Here we show RhoG, Rho GTPase related Rac, modulates dynamics. When RhoG expression is silenced, more stable live longer, resulting an increase number size adhesions, which...
Abstract SGEF, a RhoG specific GEF, can form ternary complex with the Scribble polarity proteins and Dlg1, which regulates formation maintenance of adherens junctions barrier function epithelial cells. Notably, silencing SGEF results in dramatic downregulation expression both E-cadherin ZO-1. However, molecular mechanisms involved regulation this pathway are not known. Here, we describe novel signaling governed by Scribble/SGEF/Dlg1 complex. Our show that an intact is required to maintain...
Abstract Glioblastoma (GBM) is a uniformly lethal primary intracranial neoplasm that inevitably recurs despite treatment by DNA damaging agents radiation (RT) and temozolomide (TMZ). Recurrence may be driven inherently resistant glioma stem-like cells (GSCs). GSCs have been shown to constitutive upregulation of damage response (DDR) pathways, resulting from elevated replication stress. This baseline DDR has consequently confer inherent resistance agents, TMZ/RT. However, factors mediating...
The E3 ubiquitin ligase APC/C-Cdh1 maintains the G0/G1 state, and its inactivation is required for cell cycle entry. We reveal a novel role Fas-associated protein with death domain (FADD) in through function as an inhibitor of APC/C-Cdh1. Using real-time, single-cell imaging live cells combined biochemical analysis, we demonstrate that hyperactivity FADD-deficient leads to G1 arrest despite persistent mitogenic signaling oncogenic EGFR/KRAS. further show FADD
Recent investigations by our laboratory demonstrated that skeletal muscle cell expression of intercellular adhesion molecule‐1 (ICAM‐1), an important protein the inflammatory response, augmented events myogenesis in which myotubes are forming, adding nuclei, aligning, fusing, synthesizing proteins, and hypertrophying. Our current work extended these findings incorporating pharmacological tools with vitro approach to discern underlying mechanisms associated ICAM‐1 mediated myogenesis....
Abstract Salmonella hijack host machinery in order to invade cells and establish infection. While considerable work has described the role of proteins invasion, much less is known regarding how natural variation these invasion-associated affects pathogenesis. Here we leveraged a candidate cellular GWAS screen identify genetic ARHGEF26 (Rho Guanine Nucleotide Exchange Factor 26 ) gene that renders lymphoblastoid susceptible Typhi Typhimurium invasion. Experimental follow-up redefined...