INTEGRATIVE SINGLE-CELL ATLAS OF HOST AND MICROENVIRONMENT IN COLORECTAL NEOPLASTIC TRANSFORMATION

Image
Image


OVERVIEW

COLON MAP: Colon Molecular Atlas Project

Colorectal cancer (CRC) is among the top three most prevalent cancers in global incidence and mortality. Most of these cancers develop from pre-cancerous adenomas. There is an unmet need to develop new preventive strategies and risk stratification models to decrease incidence, improve early detection, and prevent deaths from CRC.

We believe that the ability to provide the most effective precision diagnostics and preventive strategies can only be achieved with single-cell analysis. As such, we will map spatial relationships across the spectrum of normal colon, early polyps, and late adenomas, including their unique stromal and microbial microenvironments to identify unique molecular phenotypes.

Our goal will be accomplished through prospective, standardized collection and analysis of colorectal tissue, associated biospecimens, and related clinical and epidemiological data from participants undergoing colonoscopy or surgical resection. The biospecimens from these participants will be used for single-cell RNA sequencing, whole exome sequencing, multiplex immunofluorescence, species-specific bacterial fluorescence in situ hybridization, and other approaches.  Finally, the information from these approaches will be integrated to develop a single-cell pre-cancer atlas with defined molecular phenotypes for dissemination to the broader scientific community.


PRINCIPAL  INVESTIGATORS

ROBERT COFFEY, M.D.

Dr. Robert Coffey is John B. Wallace Professor of Medicine, Professor in the Department of Cell and Developmental Biology, and an Ingram Professor of Cancer Research at Vanderbilt University Medical Center. He directs the Vanderbilt Epithelial Biology Center and is principal investigator of Vanderbilt’s NCI-funded GI Specialized Programs of Research Excellence (SPORE), which focuses on colorectal cancer. He recently received an NCI Outstanding Investigator Award. His basic research focuses on the spatial compartmentalization of the EGF receptor (EGFR), its cognate ligands, and relevant signaling molecules in the context of polarized epithelial cells and how their dysregulation contributes to cancer. His lab identified a new mode of EGFR ligand signaling via exosomes, and he was a principal investigator within the U19 Common Fund initiative to understand the biogenesis and function of exosome-associated secreted RNAs. Other prior studies led by Dr. Coffey found that a pan-ERBB negative regulator, LRIG1, marks colonic stem cells and acts as a tumor suppressor in vivo. As part of a Common Fund NCI partnership grant with GE Healthcare, his lab also helped develop the optimized multiplex immunofluorescence (MxIF) platform used in this project.


KEN LAU, Ph.D.

Dr. Ken Lau earned his B.S. degree and his Ph.D. in Proteomics and Bioinformatics from the University of Toronto. After a joint postdoctoral fellowship at MIT and Massachusetts General Hospital, he joined the faculty at Vanderbilt as an Assistant Professor of Cell and Developmental Biology in 2013. Dr. Lau is an active member of the Vanderbilt Epithelial Biology Center and is currently an Associate Professor of Cell and Developmental Biology. Dr. Lau’s research revolves around how different cell populations in the gut integrate into tissue function with a specific focus on the gut’s role in microbial sensing and stem cells in colorectal cancer. His lab applies systems biology tools to understand tissue ecosystems as cell networks, spanning the realms of both experimental and computational biology. Dr. Lau has made various contributions to single-cell technologies, including multiplex microscopy, mass cytometry, and single-cell transcriptomics.


MARTHA J. SHRUBSOLE, Ph.D.

Dr. Martha Shrubsole is Research Professor of Medicine at Vanderbilt University Medical Center where she leads a research portfolio of molecular, nutritional, and interventional epidemiology. A major focus of Dr. Shrubsole’s research is to understand the etiology of gastrointestinal neoplasia. She seeks to identify and evaluate modifiable factors, biomarkers, and molecular mechanisms for the prevention, early detection, and precision-based interception of cancer and its precursor lesions with emphasis on sessile serrated polyps and conventional colorectal adenomas. Some of these areas of study include nutrients such as one-carbon metabolism, inflammatory markers, gut microbiome, molecular landscape of colorectal polyps, health disparities, and predictors of metachronous adenomas. In addition, Dr. Shrubsole has had leading roles in multiple randomized trials and large-scale epidemiologic studies based in the United States and globally.