A5068117209- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related molecular mechanisms research
- Nuclear Receptors and Signaling
- CAR-T cell therapy research
- Receptor Mechanisms and Signaling
- Genetic Neurodegenerative Diseases
- Extracellular vesicles in disease
- Cardiac Structural Anomalies and Repair
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- RNA Research and Splicing
- HVDC Systems and Fault Protection
- Biomedical Ethics and Regulation
- Epigenetics and DNA Methylation
University of Cambridge
2025
UK Dementia Research Institute
2025
Indian Institute of Science Bangalore
2021-2024
Institute for Stem Cell Biology and Regenerative Medicine
2018-2022
University of Trans-Disciplinary Health Sciences and Technology
2019-2021
Alzheimer's disease (AD) is the most frequent neurodegenerative amongst elderly. The SNPs rs429358 and rs7412 in APOE gene are common risk factor for sporadic AD, there three different alleles commonly referred to as APOE-ε2, APOE-ε3 APOE-ε4. Induced pluripotent stem cells (iPSCs) hold great promise model AD such can be differentiated vitro required cell type. Here we report use of CRISPR/Cas9 technology employed on iPSCs from a healthy individual with an APOE-ε3/ε4 genotype obtain isogenic...
Frontotemporal dementia type 3 (FTD3), caused by a point mutation in the charged multivesicular body protein 2B (CHMP2B), affects mitochondrial ultrastructure and endolysosomal pathway neurons. To dissect astrocyte-specific impact of mutant CHMP2B expression, we generated astrocytes from human induced pluripotent stem cells (hiPSCs) confirmed our findings mice. Our data provide mechanistic insights into how defective autophagy causes perturbed dynamics with impaired glycolysis, increased...
Apolipoprotein E (APOE), one of the primary lipoproteins in brain has three isoforms humans, APOE2, APOE3, and APOE4. APOE4 is most well-established risk factor increasing predisposition for Alzheimer's disease (AD). The presence allele alone shown to cause synaptic defects neurons recent studies have identified multiple pathways directly influenced by However, mechanisms underlying APOE4-induced dysfunction remain elusive. Here, we report that acute exposure cortical or synaptoneurosomes...
Protein synthesis is crucial for maintaining synaptic plasticity and signalling. Here we have attempted to understand the role of RNA binding proteins, Fragile X Mental Retardation (FMRP) Moloney Leukemia Virus 10 (MOV10) protein in N-Methyl-D-Aspartate Receptor (NMDAR) mediated translation regulation. We show that FMRP required downstream NMDAR stimulation MOV10 key specificity factor this process. In rat cortical synaptoneurosomes, association with Argonaute 2 (AGO2) forms inhibitory...
Calcium signaling is integral for neuronal activity and synaptic plasticity. We demonstrate that the calcium response generated by different sources modulates activity-mediated protein synthesis, another process essential Stimulation of NMDARs generates a synthesis involving three phases-increased translation inhibition, followed decrease in increased activation. show these phases are linked to NMDAR-mediated response. influx through elicits which necessary successive phases. L-VGCCs acts as...
Alzheimer's disease (AD) is the most common form of dementia, affecting millions people worldwide. Mutations in genes PSEN1, PSEN2 or APP are known to cause familial forms AD with an early age onset. In this study, specific pathogenic mutations gene were introduced into iPSC line from a healthy individual by use CRISPR-Cas9. The study resulted generation two new cell lines, one carrying V717I mutation and KM670/671NL mutation.
Abstract Epitranscriptome modifications are crucial in translation regulation and essential for maintaining cellular homeostasis. N6 methyladenosine (m 6 A) is one of the most abundant well-conserved epitranscriptome modifications, which known to play a pivotal role diverse aspects neuronal functions. However, m A with respect activity-mediated synaptic plasticity has not been studied. Here, we investigated modification response NMDAR stimulation. We have consistently observed that 5 min...
ABSTRACT ApoE4 isoform contributes to increased risk for Alzheimer’s Disease (AD) over the life course of individuals. Much remains unknown about biological pathways that connect APOE4 genotype with development pathology eventually leads AD, nor do we know how early in these cellular alterations begin. To answer questions, derived neural precursor cells (NPCs) from induced pluripotent stem (IPSCs) were CRISPR-edited at APOE locus. We intended characterize protein expression landscape NPCs...
Abstract Apolipoprotein E (APOE), one of the primary lipoproteins in brain has three isoforms humans – APOE2, APOE3, and APOE4. APOE4 is most well-established risk factor increasing pre-disposition for Alzheimer’s disease. The presence allele alone shown to cause synaptic defects neurons recent studies have identified multiple pathways directly influenced by However, mechanisms underlying induced dysfunction remain elusive. Here, we report that acute exposure cortical leads a significant...
Abstract Epitranscriptome modifications are crucial in translation regulation and essential for maintaining cellular homeostasis. N6 methyladenosine (m 6 A) is one of the most abundant well-conserved epitranscriptome modifications, which known to play a pivotal role diverse aspects neuronal functions. However, m A with respect activity-mediated synaptic plasticity has not been studied. Here, we investigated modification response NMDAR stimulation. We have consistently observed that upon...
Abstract Background It is increasingly becoming evident that ApoE4 isoform contributes to AD risk over the life course of individuals. Much remains unknown about biological pathways connect APOE4 genotype with development pathology eventually leads AD, nor do we know how early in these cellular alterations begin. To answer questions, derived neural precursor cells (NPCs) from induced pluripotent stem (IPSCs) were CRISPR‐edited at APOE locus (Ramakrishna et al. 2021; Schmid 2019). We intended...
Abstract Background : Frontotemporal dementia type 3 (FTD3) caused by a point mutation in the charged multivesicular body protein 2B (CHMP2B), affects mitochondrial ultrastructure and function as well endosomal-lysosomal fusion neurons. However, there is critical knowledge gap understanding how mutations CHMP2B affect astrocytes. Hence, we investigated disease mechanisms astrocytes derived from hiPSC with their impact on Methods To dissect astrocyte-specific of mutant expression, generated...
Abstract The Fragile X Mental Retardation Protein (FMRP) is an RNA Binding that regulates translation of mRNAs, essential for synaptic development and plasticity. FMRP interacts with a specific set mRNAs aids in their microtubule dependent transport through its association ribosomes. However, the biochemical role individual domains forming neuronal granules associating microtubules ribosomes currently undefined. Here, we report C-terminus domain sufficient to bind as well polysomes akin...