A5100686480- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Cellular transport and secretion
- Cancer Research and Treatments
- RNA regulation and disease
- Peptidase Inhibition and Analysis
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Signaling Pathways in Disease
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Microbial Inactivation Methods
- DNA Repair Mechanisms
- FOXO transcription factor regulation
- SARS-CoV-2 and COVID-19 Research
- Enzyme Structure and Function
- CRISPR and Genetic Engineering
- Toxin Mechanisms and Immunotoxins
- Virus-based gene therapy research
- RNA Research and Splicing
University of Southern California
2016-2025
University of Washington
2017-2025
Seattle Children's Hospital
2014-2025
Neurological Surgery
2017-2025
Harvard University
2008-2024
George Washington University
2024
Dana-Farber Cancer Institute
2024
USC Norris Comprehensive Cancer Center
2011-2023
University of Michigan
2023
U-M Rogel Cancer Center
2023
A large number of correlative studies have established that the activation unfolded protein response (UPR) alters cell's sensitivity to chemotherapeutic agents. Although induction glucose-regulated proteins (GRPs) is commonly used as an indicator for UPR, direct role GRPs in conferring resistance DNA damaging agents has not been proven. We report here without use endoplasmic reticulum (ER) stress inducers, specific overexpression GRP78 results reduced apoptosis and higher colony survival...
GRP78/BiP is a major endoplasmic reticulum (ER) chaperone protein critical for quality control of the ER, as well controlling activation ER-transmembrane signaling molecules. Through creation mouse models targeting Grp78 allele, function GRP78 in development and disease has been investigated. These led to discovery that obligatory early embryonic development. However, adult animals, preferably required cancer cell survival under pathologic conditions such tumor progression drug resistance....
Endoplasmic reticulum (ER) stress-induced apoptosis has been implicated in the development of multiple diseases. However, vivo signaling pathways are still not fully understood. In this report, through use genetically deficient mouse embryo fibroblasts (MEFs) and their matched wild-type controls, we have demonstrated that mitochondrial apoptotic pathway mediated by Apaf-1 is an integral part ER stress activates different caspases Apaf-1-dependent -independent mechanisms. search molecular...
Abstract Poor chemosensitivity and the development of chemoresistance remain major obstacles to successful chemotherapy malignant gliomas. GRP78 is a key regulator unfolded protein response (UPR). As Ca2+-binding molecular chaperone in endoplasmic reticulum (ER), maintains ER homeostasis, suppresses stress-induced apoptosis, controls UPR signaling. We report here that expressed at low levels normal adult brain, but significantly elevated glioma specimens human cell lines, correlating with...
GRP78, also known as BiP, is a central regulator of endoplasmic reticulum (ER) homeostasis due to its multiple functional roles in protein folding, ER calcium binding, and controlling the activation transmembrane stress sensors. induction GRP78/BiP represents major prosurvival arm unfolded response (UPR). However, physiological role GRP78 development not known. Using transgenic approach, we discovered that Grp78 promoter activated both trophectoderm inner cell mass (ICM) embryos at embryonic...
Abstract The unfolded protein response (UPR) is an evolutionarily conserved mechanism that activates both proapoptotic and survival pathways to allow eukaryotic cells adapt endoplasmic reticulum (ER) stress. Although the UPR has been implicated in tumorigenesis, its precise role endogenous cancer remains unclear. A major protective induction of ER chaperone GRP78/BiP, which expressed at high levels a variety tumors confers drug resistance proliferating dormant cells. To determine physiologic...
Mucormycosis is a fungal infection of the sinuses, brain, or lungs that causes mortality rate at least 50% despite first-line therapy. Because angioinvasion hallmark mucormycosis infections, we sought to define endothelial cell receptor(s) for fungi order Mucorales (the cause mucormycosis). Furthermore, since patients with elevated available serum iron, including those diabetic ketoacidosis (DKA), are uniquely susceptible mucormycosis, role iron and glucose in regulating expression such...
Stem cells generate rapidly dividing transit-amplifying that have lost the capacity for self-renewal but cycle a number of times until they exit cell and undergo terminal differentiation. We know very little type signals trigger earliest steps stem differentiation mediate to transition. show in normal intestinal epithelium, endoplasmic reticulum (ER) stress activity unfolded protein response (UPR) are induced at transition from cell. Induction ER causes loss stemness Perk-eIF2α-dependent...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 global pandemic, utilizes host receptor angiotensin-converting enzyme (ACE2) for viral entry. However, other factors might also play important roles in SARS-CoV-2 infection, providing new directions antiviral treatments. GRP78 is a stress-inducible chaperone entry and infectivity many viruses. Recent molecular docking analyses revealed putative interaction between receptor-binding domain (RBD)...
Cancer cells are commonly subjected to endoplasmic reticulum (ER) stress. To gain survival advantage, cancer exploit the adaptive aspects of unfolded protein response such as upregulation ER luminal chaperone GRP78. The finding that when overexpressed, GRP78 can escape other cellular compartments new functions regulating homeostasis and tumorigenesis represents a paradigm shift. Here, toward deciphering mechanisms whereby knockdown suppresses EGFR transcription, we find nuclear is prominent...