A5061563172- Insect Resistance and Genetics
- Cancer Cells and Metastasis
- Malaria Research and Control
- Invertebrate Immune Response Mechanisms
- Mosquito-borne diseases and control
- Insect symbiosis and bacterial influences
- Cancer and Skin Lesions
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Estrogen and related hormone effects
- Skin and Cellular Biology Research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Wnt/β-catenin signaling in development and cancer
- Insect Pest Control Strategies
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- Single-cell and spatial transcriptomics
- Biosensors and Analytical Detection
University of Colorado Anschutz Medical Campus
2020-2024
University of Colorado Denver
2024
Tata Institute for Genetics and Society
2022-2023
Institute of Bioinformatics and Applied Biotechnology
2020-2022
National Centre for Biological Sciences
2022
Yale Cancer Center
2018-2022
Biotech Park
2020-2022
Yale University
1991-2018
The mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis vectorial capacity and engineering interventions are both impeded by limitations vector's genome assembly. existing assemblies An. draft-quality contain thousands sequence gaps, potentially missing elements important for its biology evolution.
Environmental surveillance (ES) of a pathogen is crucial for understanding the community load disease. As an early warning system, ES SARS-CoV-2 has complemented routine diagnostic by capturing near real-time virus circulation at population level.In this longitudinal study conducted between January 2022 and June in 28 sewershed sites Bengaluru city (∼11 million inhabitants), we quantified weekly RNA concentrations to track infection dynamics provide evidence change relative abundance...
Abstract Background Breast cancer is a highly heterogeneous disease characterized by multiple histologic and molecular subtypes. While myriad of breast cell lines have been developed over the past 60 years, estrogen receptor alpha (ER)+ some mutations associated with this subtype remain underrepresented. Here we describe six derived from patient-derived xenografts (PDX) their general characteristics. Methods Established PDX were processed into suspensions placed standard 2D culture; emerged...
Abstract For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor (CTCs) other peripheral blood mononuclear (PBMCs) may provide valuable prognostic information. The purpose this study was to use single‐cell RNA‐sequencing (scRNA‐seq) liquid biopsies from breast patients begin defining intravascular interactions. We captured...
Progesterone receptors (PR) are potent modifiers of endocrine responses. In aberrant signalling cancer contexts, phosphorylation events dramatically alter steroid hormone receptor action.The transcriptomes primary tumours and metastases in mice harbouring ER+ breast patient-derived xenografts (PDXs) were analysed following single-cell RNAseq. vitro assays employed to delineate mechanisms resistance stemness.A 16-gene phospho-Ser294 PR (p-PR) signature predicted poor outcome cancer. Relative...
Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of world. Its fitness reported be a direct consequence adapting laying eggs over-head water tanks with street-side puddles polluted by oil and sewage. Large frequent inversions genome vectors are implicated adaptation. We report assembly strain An. type-form, collected from construction site Chennai (IndCh) 2016. The here L50 4, completes trilogy high-resolution genomes strains respect 16.5 Mbp 2Rb...
Musashi 2 (MSI2) is an RNA binding protein (RBP) that regulates asymmetric cell division and fate decisions in normal cancer stem cells. MSI2 appears to repress translation by 3' untranslated regions (3'UTRs) of mRNA, but the identity functional targets remains unknown. Here, we used individual nucleotide resolution cross-linking immunoprecipitation (iCLIP) identify direct partners integrated these data with polysome profiling obtain insights into function. iCLIP revealed specific thousands...
Malaria remains a major healthcare risk to growing economies like India and chromosome-level reference genome of Anopheles stephensi is critical for successful vector management understanding evolution using comparative genomics. We report assemblies an Indian strain, STE2, Pakistani strain SDA-500 by combining draft genomes the two strains homology-based iterative approach. The resulting assembly IndV3/PakV3 with L50 9/12 N50 6.3/6.9 Mb respectively, had scaffolds long enough building 90%...
Metabolic reprogramming remains largely understudied in relation to hormones estrogen receptor (ER) and progesterone (PR) positive breast cancer. In this study, we investigated how estrogens, progestins, or the combination, impact metabolism three ER PR cancer cell lines. We measured metabolites treated cells using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Top metabolic processes upregulated each treatment involved glucose metabolism, including Warburg...
Abstract Basal-like breast cancers (BLBC) are the most common triple-negative subtype (hormone receptor and HER2 negative) with poor short-term disease outcome commonly identified by expression of basal cytokeratins (CK) 5 17. The goal this study was to investigate whether CK5 CK17 play a role in adverse behavior BLBC cells. cell lines contain heterogeneous populations cells expressing CK5, CK17, mesenchymal filament protein vimentin. Stable shRNA knockdown either or compared non-targeting...
Cancer-associated mutations of the core splicing factor 3 B1 (SF3B1) result in selection novel 3' splice sites (3'SS), but precise molecular mechanisms oncogenesis remain unclear. SF3B1 stabilizes interaction between U2 snRNP and branch point (BP) on pre-mRNA. It has hence been speculated that a change BP is basis for 3'SS selection. Direct quantitative determination utilization however technically challenging. To define by SF3B1-mutant spliceosomes, we used an overexpression approach human...
Abstract Background The mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis vectorial capacity and engineering interventions are both impeded by limitations vector’s genome assembly. existing assemblies An. draft-quality contain thousands sequence gaps, potentially missing elements important for its biology evolution. Results To access previously intractable genomic regions, we generated reference-grade assembly full...
Abstract The tumor microenvironment (TME) is an important modulator of response and resistance to endocrine therapy in estrogen receptor alpha (ER) positive breast cancer. Endocrine highly effective at reducing burden preventing recurrence most cancers. Existing drugs work either directly by targeting tumor‐cell ER or indirectly inhibiting production stromal cells with aromatase inhibitors (AI). However, many also express the direct impact therapies on + remain unclear. In this study, we...
Abstract Environmental surveillance (ES) of a pathogen is crucial for understanding the community load disease. As an early warning system, ES SARS-CoV-2 has complemented routine diagnostic by capturing near real-time virus circulation at population level. In this longitudinal study in 28 sewershed sites Bangalore city, we quantified RNA to track infection dynamics and provide evidence change relative abundance emerging variants. We describe system using exponentially weighted moving average...
Abstract Malaria remains a major healthcare risk to growing economies like India and chromosome-level reference genome of Anopheles stephensi is critical for successful vector management an understanding evolution. We report assembly Indian strain from draft genomes two strains using homology-based iterative approach. The resulting with L50 9 had long enough scaffolds building 90% the three chromosomes physical markers. sequencing individuals reveals genetic diversity ten times higher than...
Obesity has reached epidemic proportions in the United States, emerging as a risk factor for onset of breast cancer and harbinger unfavorable outcomes [1], [2], [3]. Despite limited understanding precise mechanisms, both obesity are associated with extracellular matrix (ECM) rewiring [4], [5], [6]. Utilizing total tissue proteomics, we analyzed normal-weight (18.5 to < 25 kg/m
ABSTRACT Progesterone receptors (PR) can regulate transcription by RNA Polymerase III (Pol III), which transcribes small non-coding RNAs, including all transfer RNAs (tRNAs). We have previously demonstrated that PR is associated with the Pol complex at tRNA genes and progestins downregulate transcripts in breast tumor models. To further elucidate mechanism of PR-mediated regulation III, we studied interplay between PR, repressor Maf1, TFIIIB, a core component. ChIP-seq was performed for...
ABSTRACT Purpose The development of endocrine resistance remains a significant challenge in the clinical management estrogen receptor-positive ( ER+ ) breast cancer. Metabolic reprogramming is prominent component and potential therapeutic intervention point. However, limited understanding which metabolic changes are conserved across heterogeneous landscape cancer or how factor into ER DNA binding patterns hinder our ability to target adaptation as treatment strategy. This study uses dimethyl...
Abstract How transcription factors (TF) selectively occupy a minute subset of their binding sites from sizeable pool putative in large mammalian genomes remains an important unanswered question. In part, nucleosomes help by creating formidable barriers to TF binding. concentration itself plays crucial role the competition between TFs and nucleosomes. case nuclear receptors, ligand adds another layer complexity. Estrogen receptor alpha (ER) is classic example where its main estradiol (E2) can...