Austin N. Southard-Smith
A5038774175- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Immune cells in cancer
- Pancreatic function and diabetes
- Innovative Microfluidic and Catalytic Techniques Innovation
- Helicobacter pylori-related gastroenterology studies
- Gastrointestinal motility and disorders
- CRISPR and Genetic Engineering
- Cell Image Analysis Techniques
- IL-33, ST2, and ILC Pathways
- Inflammatory Bowel Disease
- Genetic factors in colorectal cancer
- Congenital gastrointestinal and neural anomalies
- Microfluidic and Bio-sensing Technologies
- Mycobacterium research and diagnosis
- Colorectal Cancer Treatments and Studies
- Cellular Mechanics and Interactions
- Gene Regulatory Network Analysis
- Erythrocyte Function and Pathophysiology
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- Colorectal Cancer Screening and Detection
- Pancreatic and Hepatic Oncology Research
- Immunodeficiency and Autoimmune Disorders
Washington University in St. Louis
2022-2025
James S. McDonnell Foundation
2022-2024
Vanderbilt University
2019-2022
Vanderbilt University Medical Center
2020-2022
Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic imaging atlas of the two most common human colorectal polyps, conventional adenomas serrated their resulting CRC counterparts. Integrative analysis 128 datasets 62 participants reveals WNT-driven expansion stem cells, while derive differentiated...
Countries endemic for parasitic infestations have a lower incidence of Crohn's disease (CD) than nonendemic countries, and there been anecdotal reports the beneficial effects helminths in CD patients. Tuft cells small intestine sense direct immune response against eukaryotic parasites. We investigated activities tuft patients with mouse models intestinal inflammation.
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
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...
Anti-tumor necrosis factor (anti-TNF) therapy resistance is a major clinical challenge in inflammatory bowel disease (IBD), due, part, to insufficient understanding of disease-site, protein-level mechanisms. Although proteomics data from IBD mouse models exist, and phenotype discrepancies contribute confounding translation preclinical animal cohorts. We developed an approach called translatable components regression (TransComp-R) overcome interspecies trans-omic between human subjects....
Abstract Pancreatic ductal adenocarcinoma PDAC has been observed to arise in the context of diverse pre-cancerous cystic (intraductal papillary mucinous neoplasms (IPMN) and (MCNs)) pre-cystic (pancreatic intraepithelial neoplasia (PanIN)) lesions clinic. While mouse models these precancerous have existed for a decade, only recently transcriptional signature dysplastic progression one (PanIN) thoroughly characterized at single cell resolution. Utilizing multimodal, spatial interrogation via...
The increasing demand of single-cell RNA-sequencing (scRNA-seq) experiments, such as the number experiments and cells queried per experiment, necessitates higher sequencing depth coupled to high data quality. New high-throughput sequencers, Illumina NovaSeq 6000, enables this be filled in a cost-effective manner. However, current scRNA-seq library designs present compatibility challenges with newer technologies, index-hopping, their ability generate quality has yet systematically evaluated....
Droplet-based single-cell RNA-seq (scRNA-seq) data are plagued by ambient contaminations caused nucleic acid material released dead and dying cells. This is mixed into the buffer co-encapsulated with cells, leading to a lower signal-to-noise ratio. Although there exist computational methods remove post-hoc, reliability of algorithms in generating high-quality from low-quality sources remains uncertain. Here, we assess quality before filtering set quantitative, contamination-based metrics...
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...
Swi-independent 3a and 3b (Sin3a Sin3b) are paralogous transcriptional coregulators that direct cellular differentiation, survival, function. Here, we report mouse Sin3a Sin3b coproduced in most pancreatic cells during embryogenesis but become much more enriched endocrine adults, implying continued essential roles mature cell Mice with loss of
The Gut Cell Atlas (GCA), an initiative funded by the Helmsley Charitable Trust, seeks to create a reference platform understand human gut, with specific focus on Crohn's disease. Although primary of GCA is focusing single-cell profiling, we seek provide framework integrate other analyses multi-modality data such as electronic health record data, radiological images, and histology tissues/images. Herein, use research capture (REDCap) system central tool for secure web application that...
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...
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...
Abstract Most colorectal cancers (CRCs) develop from either adenomas (ADs) or sessile serrated lesions (SSLs). The origins and molecular landscapes of these histologically distinct pre-cancerous polyps remain incompletely understood. Here, we present an atlas at single-cell resolution sporadic conventional tubular/tubulovillous ADs, SSLs, hyperplastic (HPs), microsatellite stable (MSS) unstable (MSI-H) CRC, normal colonic mucosa. Using transcriptomics multiplex imaging, studied 69 datasets...
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 Achieving high data quality in single-cell RNA-seq (scRNA-seq) experiments has always been a significant challenge stemming from minute signal that can be detected individual cells. Droplet-based scRNA-seq additionally suffers ambient contamination, comprising nucleic acid materials released by dead cells into the loading buffer and co-encapsulated with real cells, which further washes out biological signals. Here, we developed quantitative, contamination-based metrics an associated...
The role of intratumor heterogeneity is becoming increasingly apparent in part due to expansion single cell technologies. Clinically, tumor poses several obstacles effective cancer therapy dealing with biomarker variability and treatment responses. Matrix stiffening known occur during progression contribute pathogenesis hallmarks, including angiogenesis metastasis. However, the effects matrix on have not been thoroughly studied. In this study, we applied single-cell RNA sequencing...
Abstract Anti-TNF therapy resistance is a major clinical challenge in Crohn’s Disease (CD), partly due to insufficient understanding of disease-site, protein-level mechanisms CD and anti-TNF treatment resistance. Although some proteomics data from mouse models exists, type phenotype discrepancies contribute confounding attempts translate between preclinical animal disease human cohorts. To meet this important challenge, we develop demonstrate here an approach called Translatable Components...
Longitudinal analysis of Crohn's disease (CD) incidence has identified an inverse correlation with helminth infestation and recent studies have revealed that intestinal tuft cell hyperplasia is critical for response. Tuft frequency was decreased in the inflamed ilea CD patients a mouse model TNFα-induced Crohn's-like ileitis (TNFΔARE). Single-cell RNA sequencing paired unbiased differential trajectory lineage genetic (AtohKO) demonstrated had increased tricarboxylic acid (TCA) cycle gene...
Abstract The increasing demand of single-cell RNA-sequencing (scRNA-seq) experiments, such as the number experiments and cells queried per experiment, necessitates higher sequencing depth coupled to high data quality. New high-throughput sequencers, Illumina NovaSeq 6000, enables this be filled in a cost-effective manner. However, current scRNA-seq library designs present compatibility challenges with newer technologies, index-hopping, their ability generate quality has yet systematically...