Ken Lau, professor of cell and developmental biology, and Jeff Spraggins, associate professor of cell and developmental biology and director of the Mass Spectrometry Research Center, are joint project leaders on a National Cancer Institute project to build a three-dimensional, multimodal molecular atlas of colorectal cancer across different ages of disease onset.
CRC is the fourth most diagnosed cancer and the second leading cause of cancer-related deaths in the U.S. Incidence of CRC is rising at alarming rates amongst people under 50, now accounting for around 10 percent of newly diagnosed cases. The causative factors for early-onset CRC continue to befuddle scientists as these tumors are not genetically different from their average-onset counterparts.
The Vanderbilt effort will result in the first spatially mapped atlas characterizing the progression trajectories of early-onset CRC versus average-onset CRC as they transition from precancerous lesions to malignant cancers, providing insights into the causative molecular factors driving earlier onset of CRC.
Lau, Spraggins, and their team—expert epidemiologists, gastroenterologists, pathologists, surgeons, systems biologists, biochemists, bioinformaticians, and cancer biologists—will integrate advanced techniques to visualize the molecular and cellular factors associated with CRC onset, the tumor immune microenvironment, and histological status. Leveraging computational and machine learning approaches, the team will provide unprecedented insights into the genetic, transcriptomic, metabolomic, microbial, and architectural features that accelerate tumor growth.
“This effort results from a timely culmination of Vanderbilt’s world-leading technological capabilities, renowned strength in colorectal cancer research, and burgeoning expertise in computational systems biology to leverage human multimodal data to solve an emerging, medically significant problem,” Lau said. “Vanderbilt cannot be a more perfect place for this type of highly collaborative research.”
This five-year, $5 million grant will create the Vanderbilt Human Tumor Atlas Network center, which will have close ties with the national Human Tumor Atlas Network, an NCI-funded Cancer Moonshot initiative. Lau and Spraggins have served as steering committee co-chairs in the current HTAN and the Human BioMolecular Atlas Program consortium, respectively. The Vanderbilt HTAN center will be the formal collaboration among HTAN and HuBMAP and follows a pilot grant from the Vanderbilt Digestive Diseases Research Center to Lau for the development of technologies that will be leveraged in this project.
“HuBMAP has allowed us to develop a toolbox for systems biology that combines imaging mass spectrometry, multiplexed immunofluorescence, and spatial transcriptomics at cellular resolution,” Spraggins said. “We now get to apply this unique set of integrated technologies to understand how molecular distributions and cellular organization are altered in CRC.”
This multidisciplinary, multi-institute research initiative brings together a distinguished team of investigators, including:
- Robert Coffey, an internationally recognized expert with more than 30 years of continuous NCI-based funding related to studying CRC and more than a decade of collaborative research with Lau
- Martha Shrubsole, the co-leader of the Cancer Epidemiology Research Program and a principal investigator of Vanderbilt’s previous HTAN center
- Qi Liu, professor of biostatistics who recently helped identify a clinically actionable epigenetic cause of cetuximab resistance in CRC. Liu is a longstanding collaborator with Coffey and Lau.
- M. Kay Washington, chief pathologist in Vanderbilt’s previous HTAN center who will reprise her role in the new center. Washington also serves as director of the Cooperative Human Tissue Network at the Vanderbilt University Medical Center and collaborates with Coffey and Lau.
- Angela Kruse, an expert in spatial multi-omics and MSRC faculty member who has led the creation of pancreas and eye tissue atlases for the Vanderbilt HuBMAP team.
- Melissa Farrow, a cell biologist specializing in spatial biology, team lead for the HuBMAP Kidney Tissue Mapping Center, and MSRC faculty member who will serve as the project manager for the Vanderbilt HTAN center.
Other collaborators include Dr. Cynthia Sears and Abby Geis from Johns Hopkins University and Raf Van de Plas and Joana Gonçalves from the Delft University of Technology in the Netherlands.
The Lau and Coffey labs recently discovered why most colorectal tumors escape detection and destruction by the body’s immune system and received a grant from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation to support research aimed at dramatically expanding the efficacy of immunotherapy for CRC. Lau also received funding from the Stanley Cohen Innovation Fund through the School of Medicine Basic Sciences for his pathbreaking CRC research.