A5030116386- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Chronic Myeloid Leukemia Treatments
- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Epilepsy research and treatment
- Acute Myeloid Leukemia Research
- Photoreceptor and optogenetics research
- Eosinophilic Disorders and Syndromes
- Lipid Membrane Structure and Behavior
- Platelet Disorders and Treatments
- Ion channel regulation and function
- Cancer, Lipids, and Metabolism
- Cellular transport and secretion
- Computational Drug Discovery Methods
- Kruppel-like factors research
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Heme Oxygenase-1 and Carbon Monoxide
- Pharmacological Receptor Mechanisms and Effects
- Menopause: Health Impacts and Treatments
- Chemokine receptors and signaling
- Tryptophan and brain disorders
University of Zurich
2020-2024
Institute of Pharmacology
2023-2024
Medical University of Vienna
2024
ETH Zurich
2023
Maulana Azad Medical College
2014-2020
University of Delhi
2019
Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which involved sphingolipid biosynthesis, are associated with intellectual disability, but pathogenic mechanism remains obscure. Here, we characterize 31 individuals de novo missense variants CERT1. Several fall into a previously uncharacterized dimeric helical domain that enables...
Abstract Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action the mammalian brain remains unclear due to lack high-resolution approaches detect this neuropeptide appropriate spatial temporal resolution. Here we develop characterize NOPLight, genetically encoded sensor that sensitively reports changes...
The glucagon-like peptide-1 receptor (GLP1R) is a broadly expressed target of peptide hormones with essential roles in energy and glucose homeostasis, as well the blockbuster weight-loss drugs semaglutide liraglutide. Despite its large clinical relevance, tools to investigate precise activation dynamics this high spatiotemporal resolution are limited. Here, we introduce novel genetically encoded sensor based on engineering circularly permuted green fluorescent protein into human GLP1R, named...
The molecular code that controls synapse formation and maintenance in vivo has remained quite sparse. Here, we identify the secreted protein Adamtsl3 functions as critical hippocampal organizer acting through transmembrane receptor DCC (deleted colorectal cancer). Traditionally, function been associated with glutamatergic synaptogenesis plasticity response to Netrin-1 signaling. We demonstrate early post-natal deletion of neurons impairs expression, causing reduced density both GABAergic...
Abstract Cerebral ischemia is the leading cause for long‐term disability and mortality in adults due to massive neuronal death. Currently, there no pharmacological treatment available limit progressive death after stroke. A major mechanism causing ischemia‐induced excessive release of glutamate associated overexcitation neurons (excitotoxicity). Normally, GABA B receptors control excitability brain via prolonged inhibition. However, excitotoxic conditions rapidly downregulate a...
Background: Epithelial ovarian cancer continues to be a deleterious threat women as it is asymptomatic and typically detected in advanced stages. Cogent non-invasive biomarkers are therefore needed which effective apprehending the disease early Recently, miRNA deregulation has shown promising magnitude tumorigenesis. miRNA-145(miR- 145) beginning understood for its possible role development progression. In this study, we identified clinicopathological hallmarks altered owing downexpression...
Class-B1 G-protein-coupled receptors (GPCRs) are an important family of clinically relevant drug targets that remain difficult to investigate via high-throughput screening and in animal models. Here, we engineered PAClight1 P78A , a novel genetically encoded sensor based on class-B1 GPCR (the human PAC1 receptor, hmPAC1R) endowed with high dynamic range (Δ F / 0 = 1100%), excellent ligand selectivity, rapid activation kinetics ( τ ON 1.15 s). To showcase the utility this tool for vitro...
One important function of GABA B receptors is the control neuronal activity to prevent overexcitation and thereby excitotoxic death, which a hallmark cerebral ischemia. Consequently, sustained activation with selective agonist baclofen provides neuroprotection in vitro vivo models However, conditions severely downregulate receptors, would compromise neuroprotective effectiveness baclofen. On other hand, recent work suggests that stabilizes receptor expression. Therefore, we addressed...
GABA B receptors control neuronal excitability via slow and prolonged inhibition in the central nervous system. One important function of under physiological condition is to prevent neurons from shifting into an overexcitation state which can lead excitotoxic death. However, ischemic conditions, are downregulated, fostering over-excitation excitotoxicity. mechanism downregulating mediated interaction with endoplasmic reticulum (ER) stress-induced transcription factor CHOP. In this study, we...
Abstract Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action the mammalian brain remains unclear due to lack high-resolution approaches detect this neuropeptide appropriate spatial temporal resolution. Here we develop characterize NOPLight, genetically encoded sensor that sensitively reports changes...
Class-B1 G protein-coupled receptors (GPCRs) are an important family of clinically relevant drug targets that remain difficult to investigate via high-throughput screening and in animal models. Here, we engineered PAClight1 P78A , a novel genetically-encoded sensor based on class-B1 GPCR (the human PAC1 receptor, hmPAC1R) endowed with high dynamic range (ΔF/F 0 = 1100%), excellent ligand selectivity rapid activation kinetics (τ ON 1.15 sec). To showcase the utility this tool for vitro...
The glucagon-like peptide-1 receptor (GLP1R) is a broadly expressed target of peptide hormones with essential roles in energy and glucose homeostasis, as well the blockbuster weight-loss drugs semaglutide liraglutide. Despite its large clinical relevance, tools to investigate precise activation dynamics this high spatiotemporal resolution are limited. Here, we introduce novel genetically encoded sensor based on engineering circularly permuted green fluorescent protein into human GLP1R, named...
GABAB receptor-mediated inhibition is indispensable for maintaining a healthy neuronal excitation/inhibition balance. Many neurological diseases are associated with disturbed balance and downregulation of receptors due to enhanced sorting the lysosomal degradation. A key event triggering phosphorylation S867 in GABAB1 subunit mediated by CaMKIIβ. Interestingly, close exists another site, T872. Therefore, question arose as whether T872 involved downregulating this site also CaMKIIβ or protein...
Purpose: Catechol-O-methyltransferase (COMT) plays a central role in DNA repair and estrogen-induced carcinogenesis. The nonsynonymous single nucleotide polymorphism (SNP) exon 4 G > A or Val108 158Met rs4680 influences COMT enzyme activity. three phenotypes of the activities include A/A with low activity, A/G medium activity G/G high Met allele is associated enzymatic resulting higher levels prefrontal dopamine. Conversely, Val lower has been several psychiatric disorders such as panic...
Abstract The glucagon-like peptide-1 receptor (GLP1R) is a broadly expressed target of peptide hormones with essential roles in energy and glucose homeostasis, as well the blockbuster weight-loss drugs semaglutide liraglutide. Despite its large clinical relevance, tools to investigate precise activation dynamics this high spatiotemporal resolution are limited. Here we introduce novel genetically-encoded sensor based on engineering circularly-permuted green fluorescent protein into human...
RIZ1 encodes a retinoblastoma (Rb)-interacting zinc finger protein, is commonly lost or expressed at reduced levels in cancer cells. The gene locus undergoes LOH many cancers. Here, we analyzed Proline insertion–deletion polymorphism amino acid position 704 the and its association with CML. pro-704 genotypes were determined by AS-PCR 100 CML patients among which 50 CP-CML, 25 AP-CML, BC-CML. Pro704 ins/del (LOH) was detected 27% patients. ins–ins homozygosity, del–del homozygosity ins–del...
Platelet-derived growth factor receptor has been implicated in many malignant and non-malignant diseases. receptor-α is a tyrosine kinase side target for imatinib, revolutionary drug the treatment of chronic myeloid leukemia that dramatically improved survival patients. Given importance platelet-derived platelet development its inhibition by it was intriguing to analyze role relation imatinib imatinib-induced thrombocytopenia We hypothesized two known functional polymorphisms, +68GA...
Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approximately 42 million people worldwide. Juvenile myoclonic epilepsy (JME) a form of idiopathic generalized representing 5-10% all cases. Lennox-Gastaut syndrome (LGS) one severe epileptic encephalopathies childhood onset, cause which may be symptomatic, i.e., secondary to an underlying brain or cryptogenic, with no known cause. Sodium channels are integral membrane proteins play central role in...