A5059702195- Single-cell and spatial transcriptomics
- Genetic and Kidney Cyst Diseases
- Cell Image Analysis Techniques
- Cancer Cells and Metastasis
- Immune cells in cancer
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Protein Degradation and Inhibitors
- Melanoma and MAPK Pathways
- Cancer Mechanisms and Therapy
- Cancer, Hypoxia, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Ubiquitin and proteasome pathways
- Metabolism, Diabetes, and Cancer
- Protease and Inhibitor Mechanisms
- Diet, Metabolism, and Disease
- Peptidase Inhibition and Analysis
- Metabolomics and Mass Spectrometry Studies
- TGF-β signaling in diseases
Emory University
2020-2025
Piedmont Cancer Institute
2024
Winship Cancer Institute
2024
Navicent Health
2023
Johns Hopkins University
2023
National Institutes of Health
2023
University of North Carolina at Chapel Hill
2020-2021
UNC Lineberger Comprehensive Cancer Center
2020
Specialized leader cells use stable filopodia to create linear fibronectin tracks promote collective cancer invasion.
Highlights•p130Cas and βIII-tubulin support PDAC growth by enhancing MYC expression•p130Cas transcriptionally regulates through SRC-p130Cas-DOCK1-RAC1-β-catenin•Microtubules post-translationally regulate stability calpains•Triple targeting of ERK/p130Cas/tubulin with ERKi KX2-391 inhibits growthSummaryTo identify therapeutic targets for KRAS mutant pancreatic cancer, we conduct a druggable genome small interfering RNA (siRNA) screen determine that suppression BCAR1 sensitizes cancer cells to...
Phenotypic heterogeneity poses a significant hurdle for cancer treatment but is under-characterized in the context of tumor invasion. Amidst range phenotypic across solid types, collectively invading cells and single have been extensively characterized as independent modes invasion, their intercellular interactions rarely explored. Here, we isolated from heterogeneous 4T1 cell line observed extensive transcriptional epigenetic diversity these subpopulations. By integrating datasets,...
Numerous techniques have been employed to deconstruct the heterogeneity observed in normal and diseased cellular populations, including single cell RNA sequencing, situ hybridization, flow cytometry. While these approaches revolutionized our understanding of heterogeneity, isolation they cannot correlate phenotypic information within a physiologically relevant live-cell state with molecular profiles. This inability integrate phenotype—such as invasiveness, cell:cell interactions, changes...
ELMODs are a family of three mammalian paralogues that display GTPase-activating protein (GAP) activity toward uniquely broad array ADP-ribosylation factor (ARF) GTPases includes ARF-like (ARL) proteins. ubiquitously expressed in tissues, highly conserved across eukaryotes, and ancient origin, being present the last eukaryotic common ancestor. We described functions ELMOD2 immortalized mouse embryonic fibroblasts (MEFs) regulation cell division, microtubules, ciliogenesis, mitochondrial...
Abstract Metastatic disease drives cancer patient mortality. One primary mode of metastasis is collective invasion, whereby cohesive groups cells invade into the adjacent stroma while maintaining cell-cell contacts. Importantly, these cellular packs harbor genetically and phenotypically heterogeneous subpopulations that cooperate to drive invasion. To deconstruct how phenotypic heterogeneity facilitates distinct molecular profiles within a single tumor, we established technique...
Targeting cancer metabolism to limit cellular energy and metabolite production is an attractive therapeutic approach. Here, we developed analogs of the bisbiguanide, alexidine, target lung cell assess a structure-activity relationship (SAR). The SAR led identification two analogs, AX-4 AX-7, that growth via G1/G0 cell-cycle arrest are tolerated
Abstract Metastasis accounts for 90% of cancer-related deaths; however, the molecularmechanisms by which cancer cells invade and metastasize remain poorly understood.Around 80% lung patients present with metastatic disease have only a 5%5-year relative survival. Metastases are often seeded heterogeneous that invadecollectively in cellular packs. However, most studies treatments focus on bulk cellularpopulations leaving subpopulations drive metastasis masked. We previouslypublished metabolic...
ABSTRACT Numerous techniques have been employed to deconstruct the heterogeneity observed in normal and diseased cellular populations, including single cell RNA sequencing, situ hybridization, flow cytometry. While these approaches revolutionized our understanding of heterogeneity, isolation they cannot correlate phenotypic information within a physiologically relevant live-cell state, with molecular profiles. This inability integrate historical phenotype, such as invasiveness, cell:cell...
To identify therapeutic targets for KRAS-mutant pancreatic cancer, we conducted a druggable genome siRNA screen and determined that suppression of BCAR1 sensitizes cancer cells to ERK inhibition. Integrative analysis genome-scale CRISPR-Cas9 screens also identified as top synthetic lethal interactor with mutant KRAS. encodes the SRC substrate p130Cas. We inhibitor-mediated p130Cas phosphorylation impairs MYC transcription through DOCK1-RAC1-beta-catenin dependent mechanism. Additionally,...
ABSTRACT ELMODs are a family of three mammalian paralogs that display GTPase activating protein (GAP) activity towards uniquely broad array ADP-ribosylation factor (ARF) GTPases includes ARF-like (ARL) proteins. ubiquitously expressed in tissues, highly conserved across eukaryotes, and ancient origin, being present the last eukaryotic common ancestor. We described functions ELMOD2 immortalized mouse embryonic fibroblasts (MEFs) regulation cell division, microtubules, ciliogenesis,...
Numerous techniques have been employed to deconstruct the heterogeneity observed in normal and diseased cellular populations, including single cell RNA sequencing, situhybridization, flow cytometry. While theseapproaches revolutionized our understanding of heterogeneity, isolation they cannot correlate phenotypic information within a physiologically relevant live-cell state with molecular profiles. This inability integrate phenotype - such as invasiveness, cell:cell interactions, changes...