Andrew Shinkle
- Multiple Myeloma Research and Treatments
- Renal cell carcinoma treatment
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- Cancer Cells and Metastasis
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Mechanisms of cancer metastasis
- RNA modifications and cancer
- FOXO transcription factor regulation
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Genetics, Aging, and Longevity in Model Organisms
- Colorectal Cancer Treatments and Studies
- MicroRNA in disease regulation
- Glycosylation and Glycoproteins Research
- Renal and related cancers
- Advanced biosensing and bioanalysis techniques
- Mathematical Biology Tumor Growth
- Pancreatic and Hepatic Oncology Research
- Birth, Development, and Health
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
University of Kentucky
2024-2025
Washington University in St. Louis
2022-2025
Markey Cancer Center
2024
Texas A&M University
2024
Columbia University Irving Medical Center
2024
James S. McDonnell Foundation
2022-2024
Texas A&M Health Science Center
2024
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...
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,...
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...
Abstract Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single-cell transcriptomic profiling, yielding 38 marker genes encoding cell-surface proteins and 15 intracellular proteins. Of...
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 A key feature common to triple-negative breast cancer is metabolic reprogramming that contributes the malignant phenotype. Dysregulation of phosphoglycerate kinase 1 (PGK1), an essential player in glycolysis, involved several oncogenic pathways. In current study, we aimed determine whether PGK1-mediated glucose metabolism impacts induction ferroptosis cancer. We found expression PGK1 varies TNBC cell lines, with MDA-MB-231, MDA-MB-458 and MDAMB-453 lines showing significantly higher...
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 Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to heterogeneity and drug resistance. Combination therapies that leverage molecular profiles could offer an avenue enhancing efficacy addressing the limitations of current therapies. To identify effective strategies treating RCC, we selected ten drugs guided by biology test six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor...
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...
<title>Abstract</title> Triple negative breast cancer (TNBC) is a particularly lethal (BC) subtype driven by stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated protein 1 (NAC1), member of the BTB/POZ gene family, plays crucial role in TNBC maintaining tumor stemness influencing myeloid-derived suppressor (MDSCs). High NAC1 expression correlates with worse prognosis. knockdown reduced CSC markers cell proliferation, migration,...
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...
<p>Pearson R correlation values between bulk RNA expression and scRNA in PCs for target genes.</p>
<p>supplementary figures</p>
<p>supplementary figures</p>
<p>NetMHC analysis output for tissue-specific intracellular genes. Only peptides identified as strong binders (% rank <0.5) are shown. Detailed explanation of each column can be found here: http://www.cbs.dtu.dk/services/NetMHC/output.php.</p>
<p>NetMHC analysis output for tissue-specific intracellular genes. Only peptides identified as strong binders (% rank <0.5) are shown. Detailed explanation of each column can be found here: http://www.cbs.dtu.dk/services/NetMHC/output.php.</p>
<p>List of recurrent mutations with potential utility as neoantigens</p>
<p>List of recurrent mutations with potential utility as neoantigens</p>
<p>Pearson R correlation values between bulk RNA expression and scRNA in PCs for target genes.</p>