A5105513919- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Lung Cancer Research Studies
- interferon and immune responses
- Cancer therapeutics and mechanisms
- Multiple Myeloma Research and Treatments
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Cutaneous Melanoma Detection and Management
- Bone Tumor Diagnosis and Treatments
- Genomics and Phylogenetic Studies
- Radio Frequency Integrated Circuit Design
- Radiomics and Machine Learning in Medical Imaging
- Epigenetics and DNA Methylation
- Digestive system and related health
- Cancer Treatment and Pharmacology
- Chemokine receptors and signaling
- Melanoma and MAPK Pathways
- Advanced Data Storage Technologies
- Cancer-related gene regulation
University College London
2019-2023
Cancer Research UK
2019-2022
CRUK Lung Cancer Centre of Excellence
2020
University of Manchester
2016-2020
London Cancer
2020
Cancer Research UK Manchester Institute
2016-2018
Indian Institute of Technology Delhi
2010-2014
Abstract Purpose: Introduced in 1987, platinum-based chemotherapy remains standard of care for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor. Prominent barriers to progress are paucity tumor tissue identify drug targets and patient-relevant models interrogate novel therapies. Following our development circulating patient–derived explants (CDX) as that faithfully mirror patient disease, here we exploit CDX examine new therapeutic options SCLC. Experimental Design: We...
BackgroundOver the past decade, numerous reports describe generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling preclinical drug testing, requirement a biopsy limits available patient population, particularly those with advanced oligometastatic disease. Conversely, 'liquid biopsies' such as circulating tumour cells (CTCs) are minimally invasive easier to obtain. Here,...
We report here a novel method for predicting melting temperatures of DNA sequences based on molecular-level hypothesis the phenomena underlying thermal denaturation DNA. The model presented attempts to quantify energetic components stabilizing structure such as base pairing, stacking, and ionic environment which are partially disrupted during process denaturation. gives Pearson product-moment correlation coefficient (r) ∼0.98 between experimental predicted over 300 varying lengths ranging...
Patient-derived xenograft (PDX) and circulating tumor cell-derived explant (CDX) models are powerful methods for the study of human disease. In cancer research, these have been applied to multiple questions, including metastatic progression, genetic evolution, therapeutic drug responses. As PDX CDX can recapitulate highly heterogeneous characteristics a patient tumor, as well their response chemotherapy, there is considerable interest in combining them with next-generation sequencing monitor...
Expression of the transcription factor brachyury (TBXT) is normally restricted to embryo, and its silencing epigenetically regulated. TBXT promotes mesenchymal transition in a subset common carcinomas, chordoma, rare cancer showing notochordal differentiation, acts as putative oncogene. We hypothesized that expression controlled through epigenetic inhibition promote chordoma cell death. Screening five human lines revealed pharmacologic histone 3 lysine 27 demethylases KDM6A (UTX) KDM6B...
Small cell lung cancer (SCLC) is an aggressive disease with median survival of <2 years. Tumour biopsies for research are scarce, especially from extensive-stage patients, repeat sampling at progression rarely performed. We overcame this limitation relevant preclinical models by developing SCLC circulating tumour derived explants (CDX), which mimic the donor pathology and chemotherapy response. To facilitate compound screening identification clinically biomarkers, we developed short-term ex...
Abstract CD4+ T cell functional inhibition (exhaustion) is a hallmark of malaria and correlates with impaired parasite control infection chronicity. However, the mechanisms exhaustion are still poorly understood. In this study, we show that Ag-experienced (Ag-exp) during Plasmodium yoelii nonlethal occurs alongside reduction in mammalian target rapamycin (mTOR) activity restriction glycolytic capacity. We demonstrate loss metabolism mTOR within exhausted Ag-expCD4+ population coincides T-bet...
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 often fused with NuA4/TIP60 JAZF1. We show that JAZF1-SUZ12 dysregulates composition, genome occupancy, modification, expression, Loss of N terminus in fusion protein abrogates interaction specific accessory factors, reduces occupancy at target genes, diminishes...
Physicochemical properties of DNA sequences as a guide to developing insights into genome organization has received little attention. Here, we utilize the energetics further advance knowledge on its language at molecular level. Specifically, ask question whether physicochemical different functional units genomes differ. We extract intramolecular and solvation energies base pair steps from comprehensive set dynamics simulations. then investigate behavior coding for mRNAs tRNAs. Distinguishing...
We advance here a novel concept for characterizing different classes of RNA genes on the basis physico-chemical properties DNA sequences. As knowledge-based approaches could yield unsatisfactory outcomes due to limitations training available experimental data sets, alternative that utilize intrinsic are needed supplement based methods and eventually provide molecular insights into genome organization. Based comprehensive series dynamics simulations Ascona B-DNA consortium, we extracted...
The benefit of autologous stem cell transplantation (ASCT) in newly diagnosed myeloma patients, apart from supporting high dose chemotherapy, may include effects on T function the bone marrow (BM). We report our exploratory findings infiltrating cells early post-ASCT (day+100), examining phenotype and receptor (TCR) repertoire, seeking correlations with timing relapse. Compared to healthy donors (HD), we observed an increase regulatory (CD4+FoxP3+, Tregs) reduction CD4 cells, leading lower...
Treating Mucoceles in small children is a complicated task as do not sit still and cooperate during surgical procedures.Also, on seeing the armamentarium required for removal of mucocele suturing, many their parents become anxious fearful.The location size lesion also dictates, whether surgery has to be done under GA or LA.This technique involves passing 1 more sutures through base create alternate drainage pathway collected mucus so that cyst dissolves dissipates by itself thereby avoiding...
Categorical data has always posed a challenge in analysis through clustering.With the increasing awareness about Big analysis, need for better clustering methods categorical and mixed arisen.The prevailing algorithms are not suitable majorly because distance functions used continuous applicable data.Recent research focuses on several different approaches data.However, complexity of makes them unsuitable use big data.Emphasis should be which faster.Thus paper proposes simple, fast method...
Abstract Precision medicine holds great promise to improve outcomes in cancer, including haematological malignancies. However, there are few biomarkers that influence choice of chemotherapy clinical practice. In particular, multiple myeloma requires an individualized approach as exist several active therapies, but little agreement on how and when they should be used combined. We have previously shown a transcriptomic signature can identify specific bortezomib- lenalidomide-sensitivity. gene...
ABSTRACT Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain repression of genes specific for other cell types and is essential differentiation. In endometrial stromal sarcoma, the PRC2 subunit SUZ12 often fused with NuA4/TIP60 JAZF1. Here, we show that JAZF1-SUZ12 dysregulates composition, recruitment, modification, gene expression The loss N-terminus in fusion protein disrupted interaction accessory factors JARID2, EPOP PALI1 prevented recruitment...