Wagma Caravan
A5089882737- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- Renal and related cancers
- Biochemical and Molecular Research
- HIV/AIDS drug development and treatment
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Research on Leishmaniasis Studies
- Epigenetics and DNA Methylation
- Adenosine and Purinergic Signaling
- Mechanical and Optical Resonators
- Mechanisms of cancer metastasis
- Ubiquitin and proteasome pathways
- Reproductive tract infections research
- Molecular Biology Techniques and Applications
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- CAR-T cell therapy research
- AI in cancer detection
- Advanced Biosensing Techniques and Applications
- Cancer Research and Treatments
- Cell Image Analysis Techniques
- Protein Degradation and Inhibitors
James S. McDonnell Foundation
2021-2024
Washington University in St. Louis
2019-2024
Adelphi University
2018-2019
Cornell University
2019
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...
Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, transcriptomics cellular imaging. Subpopulations of tumor cells exhibited signatures proliferation, KRAS signaling, cell stress epithelial-to-mesenchymal transition. Mapping mutations copy number events distinguished populations normal transitional...
Clear cell renal carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- intratumoral heterogeneity (ITH) results in varying prognosis treatment outcomes. To obtain the comprehensive profile ccRCC, we perform integrative histopathologic, proteogenomic, metabolomic analyses on 305 ccRCC tumor segments 166 paired adjacent normal tissues from 213 cases. Combining histologic molecular profiles reveals ITH 90% ccRCCs, with 50% demonstrating immune...
Chromatin accessibility is essential in regulating gene expression and cellular identity, alterations have been implicated driving cancer initiation, progression metastasis
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,...
Non-clear cell renal carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis aggressive disease, therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, metabolic aberrations in RCC subtypes. RCCs high genome instability display overexpression IGF2BP3 PYCR1. Integration...
Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, post-translational modifications (PTMs) with transcriptomic measurements uncover multi-scale regulatory interactions governing tumor development evolution. Applying 14 proteogenomic...
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 Gliomas account for over 80% of primary malignant brain tumors. Among the most aggressive these is IDH-wildtype high-grade glioma (HGG), known as glioblastoma, which resistant to treatment and carries a median survival 15 months. Genomic transcriptomic characterization HGG demonstrate strong inter- intra-tumor heterogeneity. Distinct from IDH-mutant notably exhibit diffuse infiltrative histology with hypermethylated molecular phenotype, circumferentially organize around necrotic...
Abstract Renal cell carcinoma (RCC) is a heterogeneous malignancy with complex genetic underpinnings. While short-read sequencing has provided valuable insights into RCC genomics, the detection of large and structural variants (SVs) remains limited. In this study, we analyzed 17 pairs samples identified 555 somatic SVs in tumor using both long-read sequencing. All except repeat expansions are singleton variants, indicating high inter-tumor heterogeneity. Repeat recurrent, GAAGGG expansion...
Abstract Clear cell renal carcinoma (ccRCC) is the most prevalent subtype of carcinoma, accounting for approximately 70% cases. Strikingly, ccRCC exhibits a marked sex disparity in prevalence, being significantly more common men than women. This underscores importance systematically investigating differences to elucidate their implications diagnosis, prognosis, and therapeutic strategies ccRCC. To address this, we generated comprehensive single-nucleus sequencing atlas (snRNA-seq snATAC-seq)...
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 Renal cell carcinomas (RCC) are highly heterogeneous and aggressive cancers with diverse histological subtypes, molecular profiles, tumor microenvironments (TMEs), clinical behaviors. Intratumoral heterogeneity (ITH), a hallmark of RCC, arises from distinct subclones within the same that vary histopathologically molecularly. To elucidate biological mechanisms underlying RCC tumorigenesis at single-cell resolution, we examined 155 specimens 78 cases, encompassing clear (ccRCC),...
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...
Nanophotonic waveguides have enabled on-chip optical trap arrays for high-throughput manipulation and measurements. However, the realization of full potential these devices requires trapping enhancement applications that need large force. Here, we demonstrate a solution via fabrication high refractive index cylindrical particles. Using two different processes, cleaving method novel lift-off method, produced silicon nitride (Si3N4) particles characterized their properties using recently...
Trichomonas vaginalis infects approximately 300 million people worldwide annually. Infected individuals have a higher susceptibility to more serious conditions such as cervical and prostate cancer. The parasite has developed increasing resistance current drug therapies, with an estimated 5% of clinical cases resulting from resistant strains, creating the need for new therapeutic strategies novel mechanisms action. Nucleoside salvage pathway enzymes represent targets these pathways are...
Abstract Non-clear cell renal carcinomas (non-ccRCCs) represent ~15-20% RCCs cases comprising nearly 20 different disease subtypes and a wide spectrum of clinical behavior from benign to highly aggressive course. Clinically, metastatic non-ccRCC patients, regardless with distinct genomic aberrations, are all treated the same standard care therapies, underscoring need for precision therapeutic strategies. Diagnostic challenges also exist as malignant entities often display overlapping...
Trichomoniasis is caused by the parasitic protozoan Trichomonas vaginalis. The increasing prevalence of strains resistant to current 5-nitroimidazole treatments creates need for novel therapies. T. vaginalis cannot synthesize purine and pyrimidine rings requires salvage pathway enzymes obtain them from host nucleosides. uridine nucleoside ribohydrolase was screened using an 19F NMR-based activity assay against a 2000-compound fragment diversity library. Several series inhibitors were...
Abstract Clear cell renal carcinoma (ccRCC) is the most prevalent subtype of carcinoma, accounting for approximately 70% all cases. Therapeutic treatment metastatic ccRCC involve tyrosine kinase inhibitors or mTOR inhibiters. While these drugs extend patient survival, it also introduces a range adverse side effects. Utilizing snRNA sequencing, snATACseq, and spatial transcriptomics, two potential tumor specific markers have been identified: ceruloplasmin (CP) UCHL1. These are notably...
Abstract BAP1 mutations are associated with increased T cell and tumor-associated macrophage infiltration in clear renal carcinoma (ccRCC) predictive of poor prognosis. have also been found to be T-cell peritoneal mesothelioma uveal melanoma. Because known aggressive disease survival, we hypothesize that these lead a more immunosuppressive microenvironment. Using single nucleus RNA sequencing high-resolution spatial transcriptomics, confirmed mutant tumors immune hot high fraction Treg,...
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...