A5043032011- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Microbial Metabolic Engineering and Bioproduction
- Cancer, Hypoxia, and Metabolism
- Single-cell and spatial transcriptomics
- Advanced Proteomics Techniques and Applications
- Viral Infections and Immunology Research
- Cancer Risks and Factors
- Ferroptosis and cancer prognosis
- Diverse Musicological Studies
- Renal Transplantation Outcomes and Treatments
- Mitochondrial Function and Pathology
- Nutrition and Health in Aging
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Musicology and Musical Analysis
- Cancer-related Molecular Pathways
- Lung Cancer Treatments and Mutations
- BRCA gene mutations in cancer
- Transplantation: Methods and Outcomes
- RNA and protein synthesis mechanisms
- Cancer, Lipids, and Metabolism
Memorial Sloan Kettering Cancer Center
2022-2024
Kettering University
2024
The mitochondrial genome (mtDNA) encodes essential machinery for oxidative phosphorylation and metabolic homeostasis. Tumor mtDNA is among the most somatically mutated regions of cancer genome, but whether these mutations impact tumor biology debated. We engineered truncating mtDNA-encoded complex I gene, Mt-Nd5, into several murine models melanoma. These promoted a Warburg-like shift that reshaped microenvironments in both mice humans, consistently eliciting an anti-tumor immune response...
The extent of cell-to-cell variation in tumor mitochondrial DNA (mtDNA) copy number and genotype, the phenotypic evolutionary consequences such variation, are poorly characterized. Here we use amplification-free single-cell whole-genome sequencing (Direct Library Prep (DLP+)) to simultaneously assay mtDNA nuclear (nuDNA) 72,275 single cells derived from immortalized cell lines, patient-derived xenografts primary human tumors. Cells typically contained thousands copies, but was extensive...
Obesity is a risk factor for cancer, but whether obesity linked to specific genomic subtypes of cancer unknown. We examined the relationship between and tumor genotype in two clinicogenomic corpora. was associated with driver mutations lung adenocarcinoma, endometrial carcinoma cancers unknown primaries, independent clinical covariates, demographic factors genetic ancestry. therefore etiological heterogeneity some cancers. Analysis pan-cancer sequencing finds that body mass index associates...
Abstract Out of the thousands metabolites in a given specimen, most metabolomics experiments measure only hundreds, with poor overlap across experimental platforms. Here, we describe Metabolite Imputation via Rank-Transformation and Harmonization (MIRTH), method to impute unmeasured metabolite abundances by jointly modeling covariation datasets which have heterogeneous coverage features. MIRTH successfully recovers masked both within single multiple, independently-profiled datasets....
Abstract Obesity is a leading risk factor for cancer, but whether obesity linked to specific genomic subtypes of cancer unknown. Here, we examined the relationship between and tumor genotype in two large clinicogenomic corpora. was associated with driver mutations lung adenocarcinoma, endometrial carcinoma, cancers unknown primary, independent clinical covariates genetic ancestry. therefore putative etiologic heterogeneity across cancers.
Abstract Tumor metabolism is controlled by coordinated changes in metabolite abundance and gene expression, but simultaneous quantification of metabolites transcripts primary tissue rare. To overcome this limitation study gene-metabolite coregulation cancer, we assembled the Cancer Atlas Metabolic Profiles (cAMP) metabolomic transcriptomic data from 988 tumor/normal specimens spanning 11 cancer types. Meta-analysis cAMP revealed two classes Gene-Metabolite Interactions (GMIs) that...
Summary The mitochondrial genome encodes essential machinery for respiration and metabolic homeostasis but is paradoxically among the most common targets of somatic mutation in cancer genome, with truncating mutations respiratory complex I genes being over-represented 1 . While DNA (mtDNA) have been associated both improved worsened prognoses several tumour lineages 1–,3 , whether these are drivers or exert any functional effect on biology remains controversial. Here we discovered that...
Abstract The vast majority of recurrent somatic mutations arising in tumors affect protein-coding genes the nuclear genome. Here, through population-scale analysis 15,619 whole tumor genomes, we report discovery highly affecting both small (12S, MT - RNR1) and large (16S, RNR2) RNA subunits mitoribosome. In total, identified 70 recurrent, hotspot either subunit Compared to non-hotspot positions, rRNA hotspots preferentially positions participating Watson-Crick base pairing, tend arise at...
Abstract Cachexia is a debilitating syndrome characterized by loss of skeletal muscle tissue that affects over 50% cancer patients. Defining cachexia for the purposes epidemiologic analyses has historically been determined specific weight time, and more recently relied on technically challenging interpretation imaging studies. Subjective appetite or (AWL) as documented from clinician notes may offer another method defining similar phenotype. Although annotation free-text at scale...