A5036773947- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Mast cells and histamine
- Food Allergy and Anaphylaxis Research
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Tryptophan and brain disorders
- Complement system in diseases
- Transgenic Plants and Applications
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Computational Drug Discovery Methods
- Multiple Myeloma Research and Treatments
Medical University of South Carolina
2025
Hebrew University of Jerusalem
2019-2024
Instituto de Investigaciones Biomédicas Sols-Morreale
2020
Universidad Autónoma de Madrid
2020
Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
2020
Instituto de Salud Carlos III
2020
Abstract IRE1, PERK, and ATF6 are the three transducers of mammalian canonical unfolded protein response (UPR). GSK2606414 is a potent inhibitor while KIRA6 inhibits kinase activity IRE1. Both molecules frequently used to probe biological roles UPR in cells. In direct binding assay, bound cytoplasmic domain KIT with dissociation constants ( K d ) value 664 ± 294 nM whereas showed 10.8 2.9 µM. silico docking studies confirmed compact interaction ATP pocket. cultured cells, inhibited tyrosine...
The integrated stress response (ISR) converges on eIF2α phosphorylation to regulate protein synthesis. ISR is activated by several conditions, including endoplasmic reticulum (ER) stress, executed kinase R-like (PERK). We report that ER combined with inhibition causes an impaired maturation of tyrosine receptors (RTKs), consistent a partial block their trafficking from the Golgi. Other proteins mature or are secreted normally, indicating selective retention in (sERr). sERr relieved upon...
Abstract Immunotherapy has transformed cancer treatment, yet durable responses to immune checkpoint blockade (ICB) are limited a subset of patients. Identifying tumor-intrinsic resistance mechanisms is critical improving ICB efficacy and outcomes. We recently identified crosstalk between lipid metabolism via the downregulation ceramide synthase 4 (CerS4) internalized programmed death-ligand 1 (PD-L1) signaling, which promotes metastasis impairs response. Our data also demonstrated that...
Schizophrenia is a mental disease that results in decreased life expectancy and well-being by promoting obesity sedentary lifestyles. treated antipsychotic drugs. Although the second-generation antipsychotics (SGA), Olanzapine Aripiprazole, are more effective treating schizophrenia, they display higher risk of metabolic side effects, mostly development diabetes insulin resistance, weight gain, dyslipidemia. Endoplasmic reticulum (ER) stress induced when ER homeostasis lipid biosynthesis...
Conditions of endoplasmic reticulum (ER) stress reduce protein synthesis by provoking translation regulation, governed the eIF2α kinase PERK. When PERK is inhibited during ER stress, retention a selective subset glycoproteins occurs, phenomenon we termed (sERr). sERr clients are enriched with tyrosine receptors (RTKs), which form large molecular weight disulfide bonded complexes in ER. The isomerase ERp44 promotes and increases size complexes. Here show that reversible upon washout. Pulse...
The endoplasmic reticulum (ER) is a dynamic organelle that responds to demand in secretory proteins by undergoing expansion. mechanisms control the homeostasis of ER size and function involve activation unfolded protein response (UPR). UPR plays role various effector functions immune cells. Mast cells (MCs) are highly granular tissue-resident key drivers allergic inflammation. Their diverse through high-affinity receptor for IgE (FcεRI) suggest their function. Using human cord blood-derived...
Abstract Multiple myeloma (MM) causes approximately 20% of deaths from blood cancers. Notwithstanding significant therapeutic progress, such as with proteasome inhibitors (PIs), MM remains incurable due to the development resistance. mTORC1 is a key metabolic regulator, which frequently becomes dysregulated in cancer. While reduce viability and synergize other therapies vitro, clinically, are not effective for MM. Here we show that inactivation an intrinsic response PI treatment. Genetically...