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.
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.
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.
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.