UVA’s Center for Systems Analysis of Stress-adapted Cancer Organelles (SASCO) hosted this summer its second annual symposium, showcasing the latest cancer systems biology research focused on sub-cellular components and their role in the disease.
Established in 2022 with a $12 million National Cancer Institute (NCI) U54 research grant and co-led by Kevin Janes, PhD, the John Marshall Money Professor of Biomedical Engineering, and Matthew J. Lazzara, PhD, Professor of Chemical and Biomedical Engineering, SASCO pursues new targets for cancer prevention, detection and treatment, with three primary research projects focusing on breast cancer, colorectal cancer, and glioblastoma.
“The projects look at separate cancers, and the organelles that are stressed in the context of those cancers. The goal is to use systems approaches to understand how those cancers adapt to the stress on the organelles, and overcome it with the ultimate viewpoint that those stresses and adaptations create targetable vulnerabilities in the end that one might think about focusing on for therapeutics,” Dr. Lazzara said.
SASCO is part of the of the NCI Cancer Systems Biology Consortium, a group of nine U54 research centers and 21 research projects focused on cancer biology research that adopt a research approach focused on iterations between quantitative experiments and mathematical models.
This year’s event drew approximately 100 participants and spotlighted nine publications, multiple preprints and 16 invited talks since the inaugural SASCO symposium in 2024.
Keynote speaker Andrew Gentles, PhD, Associate Professor of Pathology, Medicine and Biomedical Data Science at the Stanford Center for Cancer Systems Biology, shared new insights gained from research using a variety of computational methods to identify cellular links between specific genetic profiles and cancer outcomes.
“In each data set, we know the association between the level of gene expression of each gene at diagnosis with the outcome for patients in that particular data set,” Gentles said, adding that “We can actually go from cell states to cell ecosystems in terms of predicting clinical outcomes” toward the ultimate goal of identifying predictive cell types.
SASCO researchers presented the latest progress on the program’s three main research projects and supporting work.
Todd Stukenberg, PhD, Professor, Biochemistry and Molecular Genetics, presented population-health research on molecular pathways related to health disparities in triple-negative breast cancer, which was complemented by presentations on the same pathway and cancer subtype from two Janes Lab researchers: postdoctoral trainee Sarah Groves, PhD, and Biochemistry and Molecular Genetics MD-PhD candidate Jeffrey Hsu. The overall project seeks to examine the role of a dynamic organelle that forms during cell division, which is important for the proper separation of chromosomes between daughter cells.
Jennifer Kashatus, Senior Lab Specialist in the Kashatus Lab, presented on the separation of mitochondrial proteins that occurs when this organelle is fragmented in colorectal cancer. Using a quantitative model from the SASCO team, she predicted that a key metabolic enzyme was at such a low abundance that its protein copies would not distribute equally in fragmented mitochondria. This prediction was validated with high-resolution images of the enzyme in 3D-reconstructed mitochondria from colorectal cancer cells.
Sarah Lee, PhD graduate in the Lazzara Lab, focused on organelles that form at the plasma membrane when cells receive growth signals from their environment. The number and movement of these compartments from the cell surface impact how normal and cancer cells process this information to grow, change state, or move.
SASCO relies heavily on microscopic imaging to count and track organelles within cells. As part of the Center’s imaging core, Professor of Biomedical Engineering Gustavo Rohde, PhD, and Biomedical Engineering postdoctoral fellow Zeinab Chitforoush, PhD of the Fallahi-Sichani Lab, presented updates on high-dimensional imaging and analysis of cells and chromosomes. By painting these features with different colors that mark proteins of interest, SASCO investigators can define cellular properties in molecular terms.
The day wrapped up with lightning talks and a poster session with prizes awarded to Vicki Remley, a PhD candidate in the Department of Pathology’s Molecular and Cellular Basis of Disease Program and the Department of Surgery, and a member of the Bauer and Kashatus Labs; Catalina Alvarez, a Biomedical Engineering PhD candidate of the Janes Lab; and Varna Selvakumar, an undergraduate in the Bauer Lab.
Dr. Janes concluded by saying, “We are happy to make the annual NCI site visit of SASCO open to the UVA Comprehensive Cancer Center and the University as a whole. Cancer systems biology should welcome as many perspectives as possible in tackling cancer as a complex disease.”
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