Alla Karpova
A5042931968- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Renal cell carcinoma treatment
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Advanced Proteomics Techniques and Applications
- Telomeres, Telomerase, and Senescence
- Bioinformatics and Genomic Networks
- Cancer Cells and Metastasis
- Renal and related cancers
- AI in cancer detection
- Immune cells in cancer
- Colorectal Cancer Treatments and Studies
- Barrier Structure and Function Studies
- MicroRNA in disease regulation
- Image Processing and 3D Reconstruction
- Advanced Fluorescence Microscopy Techniques
- Mathematical Biology Tumor Growth
- Neurological Disease Mechanisms and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Gene Regulatory Network Analysis
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- Gene expression and cancer classification
Washington University in St. Louis
2019-2024
James S. McDonnell Foundation
2020-2023
N. I. Lobachevsky State University of Nizhny Novgorod
2018
Privolzhsky Research Medical University
2018
To elucidate the deregulated functional modules that drive clear cell renal carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration proteogenomic measurements uniquely protein dysregulation cellular mechanisms impacted by alterations, including...
Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification metabolomic data on 99 treatment-naive GBMs provides insights GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 PLCG1) as potential switches mediating oncogenic pathway activation, well targets for EGFR-, TP53-, RB1-altered tumors. Immune...
The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued preserve post-translational modifications, including protein phosphorylation acetylation. Proteogenomics challenged standard cancer diagnoses, provided detailed analysis the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint...
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences perturbations to the p53 Wnt/β-catenin pathways, identified potential role for circRNAs in epithelial-mesenchymal transition, provided information about proteomic markers clinical genomic tumor subgroups, including relationships known druggable pathways. An extensive genome-wide...
Chromatin accessibility is essential in regulating gene expression and cellular identity, alterations have been implicated driving cancer initiation, progression metastasis
To study the spatial interactions among cancer and non-cancer cells
Abstract Identifying tumor-cell-specific markers and elucidating their epigenetic regulation spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq snATAC-seq in 34 28 human clear cell renal carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific through a multi-omics tiered approach, reveal an association between higher ceruloplasmin ( CP ) expression reduced survival. knockdown,...
Abstract Viruses drive carcinogenesis in human cancers through diverse mechanisms that have not been fully elucidated but include promoting immune escape. Here we investigated associations between virus-positivity and pathway alteration for 2009 tumors across six virus-related cancer types. Analysis revealed 3 of 72 papillomavirus (HPV)-positive head neck squamous cell carcinoma (HNSC) the HPV genome integrated checkpoint genes PD-L1 or PD-L2 , driving elevated expression corresponding gene....
There is a sex bias in the incidence and progression of many kidney diseases. To better understand such sexual dimorphism, we integrated data from six platforms, characterizing 76 samples 68 mice at developmental adult time points, creating molecular atlas mouse across lifespan for both sexes. We show that proximal tubules have most sex-biased differentially expressed genes emerging after 3 weeks age are associated with hormonal regulations. reveal potential mechanisms involving direct...
Abstract scATAC-seq data presents unprecedented opportunities to identify somatic mutations in regulatory regions. However, existing tools struggle reliably detect from due the unbalanced coverage between tumor and normal cells. To address this, we developed scVar, a pipeline designed data. Applying scVar snATAC-Seq about 200 samples spanning 10 cancer types, identified over 70, 000 mutations, with 95% located non-coding Comparison bulk WGS WXS demonstrated that achieves high accuracy...
Abstract Liver senescence involves the gradual deterioration of hepatic cell function and reduction regenerative capacity due to aging, chronic liver disease, cancer. To elucidate role in aging cancer, we employed single-cell sequencing, spatial omics, imaging approaches, collectively over 100 assays, characterize 43 normal samples from a cohort 95 donors, across ages selected based on histology clinical data. We conducted similar assays 24 patients with colorectal cancer metastasis liver....
Abstract Breast cancer (BC) is defined by distinct molecular subtypes with different cells of origin. The transcriptional networks that characterize the subtype-specific tumor-normal lineages are not established. In this work, we applied bulk, single-cell and single-nucleus multi-omic techniques as well spatial transcriptomics multiplex imaging on 61 samples from 37 patients BC to show characteristic links in gene expression chromatin accessibility between their putative Regulatory network...
Abstract Accurately defining spatial characteristics of tumors has been a challenge in cancer research. Specifically, there is still lack transcriptomic (ST) bioinformatic methods that infer tumor boundaries, necessity for microenvironment (TME) analyses, are fully automated and handle non-rectangular grids (like the one found Visium). Here we introduce Morph, toolset not only addresses these limitations, but also accurately extracts regions, layers surrounding them, distances related to...
Abstract A comprehensive understanding of the spatial localization cellular processes is necessary to fully describe tissue biology. Numerous techniques exist identify neighborhoods in datasets, however, these are limited that they either only capture two-dimensional phenomena - and can't full, 3-dimensional tumor volume, or restricted one technology (i.e. IF, 10X Visium, Xenium, MERFISH, etc.). To address this, we developed Mushroom, a tool for identification three-dimensional...
Abstract Patients with ductal carcinoma in situ (DCIS) are frequently overtreated. Identifying markers that accurately predict which cases of would progress to invasive (IDC) is crucial personalized medicine but remains a challenge. Deciphering the process DCIS progression at cellular, molecular and genetic levels helps identify biomarkers, allowing for better informed clinical decision-making. To study signatures associated from IDC, we collected samples breast cancer patients co-occurring...
Abstract Liver senescence, marked by the progressive decline in hepatic cell function and regenerative capacity, plays a vital role context of aging, chronic liver diseases, cancer progression, particularly when influenced anti-cancer therapies. This study is designed to extensively characterize senescence under two specific conditions: replicative aging therapy-induced changes. We examined samples from 20 individuals, covering wide age range (young, <40 years; old, >60 years),...
Abstract Several immune cell types have been successfully targeted for immunomodulatory therapy; however, the efficacies of such therapies are hindered by incompatible activation states. CD8+ T-cell exhaustion is one most studied states in context cancer and was shown to limit checkpoint blockade efficacy. Although studies mice showed this state tightly regulated chromatin accessibility cis-regulatory elements (CREs) transcription factor activation, exploration these mechanisms, their...
Breast cancer is a heterogeneous disease, and treatment guided by biomarker profiles representing distinct molecular subtypes. arises from the breast ductal epithelium, experimental data suggests subtypes have different cells of origin within that lineage. The precise for each subtype transcriptional networks characterize these tumor-normal lineages are not established. In this work, we applied bulk, single-cell (sc), single-nucleus (sn) multi-omic techniques as well spatial transcriptomics...
The use of single-cell methods is expanding at an ever-increasing rate. While there are established algorithms that address cell classification, they limited in terms cross platform compatibility, reliance on the availability a reference dataset and classification interpretability. Here, we introduce Pollock, suite for type identification compatible with popular analysis platforms, provides set pretrained human cancer models, reports interpretability scores identify genes drive...
Abstract Glioblastoma (GBM) is the most aggressive nervous system cancer, with median survival under 2 years. Understanding its molecular pathogenesis crucial for improving diagnosis and treatment. We performed an integrated analysis of genomic, proteomic, post-translational modification metabolomic data on 99 treatment-naive GBMs. identified key phosphorylation events (e.g., phosphorylated PTPN11 PLCG1) as potential switches mediating oncogenic pathway activation well targets EGFR-, TP53-...
Abstract Glioblastoma (GBM) is the most aggressive nervous system cancer, with median survival under 2 years. Understanding its molecular pathogenesis crucial for improving diagnosis and treatment. We performed an integrated analysis of genomic, proteomic, post-translational modification metabolomic data on 99 treatment-naive GBMs. identified key phosphorylation events (e.g., phosphorylated PTPN11 PLCG1) as potential switches mediating oncogenic pathway activation well targets EGFR-, TP53-...