John Lalith Charles Richard

ORCID: 0000-0002-1186-6390
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About
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Research Areas
  • RNA Research and Splicing
  • Cancer Cells and Metastasis
  • Cancer-related molecular mechanisms research
  • Genomics and Chromatin Dynamics
  • RNA and protein synthesis mechanisms
  • Pancreatic and Hepatic Oncology Research
  • RNA modifications and cancer
  • Phagocytosis and Immune Regulation
  • 3D Printing in Biomedical Research
  • Extracellular vesicles in disease
  • DNA Repair Mechanisms
  • Ubiquitin and proteasome pathways
  • Immune Cell Function and Interaction
  • Single-cell and spatial transcriptomics
  • Vector-Borne Animal Diseases
  • CRISPR and Genetic Engineering
  • Synthesis and properties of polymers
  • Bone Tissue Engineering Materials
  • Circular RNAs in diseases
  • Melanoma and MAPK Pathways
  • Hippo pathway signaling and YAP/TAZ
  • RNA regulation and disease
  • Cancer Mechanisms and Therapy
  • Nuclear Structure and Function
  • interferon and immune responses

University of California, San Diego
2021-2024

La Jolla Bioengineering Institute
2021-2024

Madhya Pradesh Bhoj Open University
2021

Barkatullah University
2021

Genome Institute of Singapore
2018

National University of Singapore
2017-2018

Agency for Science, Technology and Research
2018

National University Cancer Institute, Singapore
2017-2018

University of Cincinnati Medical Center
2014-2017

Cincinnati Children's Hospital Medical Center
2014-2017

Abstract Dynamically organized chromatin complexes often involve multiplex interactions and sometimes chromatin-associated RNA 1–3 . Chromatin complex compositions change during cellular differentiation ageing, are expected to be highly heterogeneous among terminally differentiated single cells 4–7 Here we introduce the multinucleic acid interaction mapping in (MUSIC) technique for concurrent profiling of interactions, gene expression RNA–chromatin associations within individual nuclei. When...

10.1038/s41586-024-07239-w article EN cc-by Nature 2024-03-27

While CRISPR-Cas systems hold tremendous potential for engineering the human genome, it is unclear how well each system performs against one another in both non-homologous end joining (NHEJ)-mediated and homology-directed repair (HDR)-mediated genome editing.

10.1186/s13059-018-1445-x article EN cc-by Genome biology 2018-05-29

Abstract The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether architecture modulates spatial distribution of caRNA vice versa. Here, we generate a resource genome-wide RNA-DNA DNA-DNA contact maps human cells. These reveal chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined domains. Further, spreading constrained boundaries topologically associating (TADs),...

10.1038/s41467-023-42274-7 article EN cc-by Nature Communications 2023-10-16

RAF kinase inhibitors are clinically active in patients with BRAF (V600E) mutant melanoma. However, rarely do tumors regress completely, the majority of responses being short-lived. This is partially mediated through loss negative feedback loops after MAPK inhibition and reactivation upstream signaling. Here, we demonstrate that deubiquitinating enzyme USP28 functions a loop to destabilize family members. Loss stabilizes enhancing downstream activation promotes resistance inhibitor therapy...

10.1084/jem.20171960 article EN cc-by The Journal of Experimental Medicine 2018-06-07

Histone variants within the H2A family show high divergences in their C-terminal regions. In this work, we have studied how these and particular, a part of COOH-terminus, docking domain, is implicated both structural functional properties nucleosome. Using biochemical methods combination with Atomic Force Microscopy Electron Cryo-Microscopy, that H2A-docking domain key feature Deletion or replacement incomplete from variant H2A.Bbd results significant alterations nucleosome, including an...

10.1093/nar/gkq1174 article EN cc-by-nc Nucleic Acids Research 2010-12-03

NF-κB is a key transcription factor regulating the expression of inflammatory responsive genes. How binds to naked DNA templates well documented, but how it interacts with chromatin far from being clear. Here we used combination UV laser footprinting, hydroxyl footprinting and electrophoretic mobility shift assay investigate binding nucleosomal templates. We show that p50 homodimer able bind its recognition sequence, when localized at edge core particle, not sequence interior nucleosome....

10.1371/journal.pgen.1003830 article EN cc-by PLoS Genetics 2013-09-26

FACT, in addition to its role transcription, is likely implicated both transcription-coupled nucleotide excision repair and DNA double strand break repair. Here, we present evidence that FACT could be directly involved Base Excision Repair elucidate the chromatin remodeling mechanisms of during BER. We found that, upon oxidative stress, released from transcription related protein complexes get associated with proteins remodelers SWI/SNF family. also showed rapid recruitment site damage,...

10.1371/journal.pgen.1006221 article EN cc-by PLoS Genetics 2016-07-28

Long non-coding RNA Xist plays a crucial role in establishing and maintaining X-chromosome inactivation (XCI) which is paradigm of long RNA-mediated gene regulation. has Xist-specific repeat elements A-F are conserved among eutherian mammals, underscoring their functional importance. Here we report that E, element the exon 7, interacts with ASH2L contributes to maintenance escape expression level on inactive (Xi) during XCI. The E-deletion mutant female ES cells show depletion from Xi upon...

10.1371/journal.pgen.1006890 article EN cc-by PLoS Genetics 2017-07-07

Adenosine-to-inosine (A-to-I) RNA editing displays diverse spatial patterns across different tissues. However, the human genome encodes only two catalytically active enzymes (ADAR1 and ADAR2), suggesting that other regulatory factors help shape landscape. Here, we show splicing factor SRSF9 selectively controls of many brain-specific sites in primates. is more lowly expressed brain than non-brain Gene perturbation experiments minigene analysis candidate demonstrated could robustly repress...

10.1093/nar/gky615 article EN cc-by-nc Nucleic Acids Research 2018-06-26

Abstract Background Pancreatic cancer is one of the most difficult cancers to detect early and patients die from complications arising due distant organ metastases. The lack bona fide biomarkers primary reasons for late diagnosis pancreatic cancer. It a multifactorial disease warrants novel approach identify biomarkers. Methods In order characterize proteome, Extracellular vesicles (EVs) isolated different in vitro conditions mimicking tumor-microenvironment interactions between epithelial...

10.1186/s13046-022-02425-y article EN cc-by Journal of Experimental & Clinical Cancer Research 2022-08-24

Combining RNA fluorescent in situ hybridization (FISH) with immunofluorescence (immuno-FISH) creates a technique that can be employed at the single cell level to detect spatial dynamics of localization simultaneous insight into proteins, epigenetic modifications and other details which highlighted by immunofluorescence. X-chromosome inactivation is paradigm for long non-coding (lncRNA)-mediated gene silencing. X-inactive specific transcript (Xist) lncRNA accumulation (called an Xist cloud)...

10.3791/52053 article EN Journal of Visualized Experiments 2014-11-26

Tumor cells dissociate from the primary site and enter into systemic circulation (circulating tumor cells, CTCs) either alone or as microemboli (clusters); latter having an increased predisposition towards forming distal metastases than single CTCs. The formation of clusters is, in part, created by contacts between cell–cell junction proteins and/or cytokine receptor pairs with other such neutrophils, platelets, fibroblasts, etc. In present study, we provide evidence for extravesicular (EV)...

10.3390/cancers13112727 article EN Cancers 2021-05-31

SUMMARY PARAGRAPH The dynamically organized chromatin complexes often involve multiplex interactions and sometimes chromatin-associated RNA (caRNA) 1–3 . Chromatin complex compositions change during cellular differentiation aging, are expected to be highly heterogeneous among terminally differentiated single cells 4–7 Here we introduce the Mu lti-Nucleic Acid Interaction Mapping in Si ngle C ell (MUSIC) technique for concurrent profiling of interactions, gene expression, RNA-chromatin...

10.1101/2023.06.28.546457 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2023-06-29

Abstract The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether architecture modulates spatial distribution of caRNA vice versa. Here, we generate a resource genome-wide RNA-DNA DNA-DNA contact maps human cells. These reveal chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined domains. Further, spreading constrained boundaries topologically associating (TADs),...

10.1101/2021.06.10.447969 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2021-06-11

RNA-protein interactions are crucial for regulating gene expression and cellular functions, with their dysregulation potentially impacting disease progression. Systematically mapping these is resource-intensive due to the vast number of potential RNA protein interactions. Here, we introduce PRIM-seq (Protein-RNA Interaction Mapping by sequencing), a method concurrent

10.1101/2024.09.04.611288 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2024-09-04

Bronchopulmonary dysplasia (BPD), a chronic lung disease, is the most common major complication of preterm birth. Supplemental oxygen administration, while lifesaving in neonatal period, remains key determinant BPD pathophysiology. Exposure immature to increased levels elicits an inflammatory response resulting abnormal development. However, not every premature infant equally sensitive develop BPD. Using genetically diverse mouse strains, we show that innate immune activated lungs mice...

10.1101/2024.09.13.612775 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-09-19

Background: Current strategies in circulating tumor cell (CTC) isolation pancreatic cancer heavily rely on the EpCAM and cytokeratin status. is generally not considered a good marker given its transitory change during Epithelial to Mesenchymal Transition (EMT) or reverse EMT. There need identify other surface markers capture complete repertoire of PDAC CTCs. The primary objective study characterize alternate biomarkers CTCs that express low negligible levels patients. Methods: Flow cytometry...

10.3390/biomedicines10081983 article EN cc-by Biomedicines 2022-08-16

Combining RNA fluorescent in situ hybridization (FISH) with immunofluorescence (immuno-FISH) creates a technique that can be employed at the single cell level to detect spatial dynamics of localization simultaneous insight into proteins, epigenetic modifications and other details which highlighted by immunofluorescence. X-chromosome inactivation is paradigm for long non-coding (lncRNA)-mediated gene silencing. X-inactive specific transcript (Xist) lncRNA accumulation (called an Xist cloud)...

10.3791/52053-v article EN Journal of Visualized Experiments 2014-11-26
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