Participants at this year’s third-annual SASCO Symposium.
UVA’s Center for Systems Analysis of Stress-adapted Cancer Organelles (SASCO) recently held its annual symposium, hosting a pair of leading figures in breast cancer research and sharing findings including identification of a new potential avenue for developing treatments for colon cancer.
While basic-science cancer research often drills down on specific disease factors, SASCO studies the effects of oncogenes on sub-cellular components (organelles) at the system level. Its three primary projects address breast and colorectal cancer and glioblastoma through computational and experimental research. Established in 2022 with a five-year, $12 million National Cancer Institute U54 grant, SASCO is a member of the multi-institution, NCI-supported Cancer Systems Biology Consortium.
“Four years into the Center’s work, we were excited with this year’s symposium to shift from presenting research-in-progress to sharing findings, which we’re increasingly hopeful will lead to therapeutic discoveries benefitting patients,” said Kevin Janes, PhD, SASCO co-lead and the John Marshall Money Professor of Biomedical Engineering.
Associate Professor of Microbiology, Immunology, and Cancer Biology Dave Kashatus, PhD, shared his team’s discovery that when colon cancer cells fragment their mitochondria, a key metabolic pathway for the cancer’s growth fragments with them, presenting a potential target for inhibitor therapy.
Biomedical Engineering PhD candidate Alexander DeWalle of the Lazzara Lab presents at this year’s SASCO Symposium.
SASCO Co-Lead and Professor of Chemical and Biomedical Engineering Matthew Lazzara, PhD, presented on his team’s pursuit of methuosis or “death by drinking” in glioblastoma cells. They found that cytoskeletal changes combined with RAS oncogene activity help glioblastoma cells survive nutrient-poor tumor microenvironments to a point, but that runaway activities of these processes without cellular adaptation surprisingly lead to cell death. Studying the adaptation mechanisms may identify new cancer vulnerabilities.
“It’s more evident than ever that the individual projects are working collaboratively on common problems,” Dr. Lazzara said, noting that his glioblastoma team’s work involving mitochondrial morphology was inspired by that of Dr. Kashatus’ team. Meanwhile, a new cross-consortium project with Dennis Discher, PhD, the Robert D. Bent Professor of Chemical and Biomolecular Engineering at the University of Pennsylvania, involves SASCO’s breast cancer team and focuses on how chromosome numbers change in cancer.
The symposium featured dual keynotes from UNC School of Medicine and Lineberger Comprehensive Cancer Center colleagues Chuck Perou, PhD, the May Goldman Shaw Distinguished Professor of Molecular Oncology and Co-Leader of UNC Lineberger’s Breast Cancer Research Program, and Lisa Carey, MD, ScM, FASCO, the L. Richardson and Marilyn Jacobs Preyer Distinguished Professor for Breast Cancer Research and UNC Lineberger’s Deputy Director for Clinical Sciences.
Introduced by Dr. Janes as “the founding father” of cancer transcriptomics, who in 2000 established the five primary molecular subtypes of breast cancer, Dr. Perou shared new advancements in disease profiling and assay development. He argued that intrinsic molecular profiling combined with measures of patients’ immune cell microenvironment can better support personalized treatments.
While early detection and improved therapies have improved breast cancer outcomes in recent decades, Dr. Carey noted that available biomarkers do not adequately reflect differences within subtypes, so development of new assays to guide clinical decision-making has lagged. The gap is especially impactful in early breast cancer, and better understanding of genomic, phenotypic, and immune features is needed to improve its treatment, she said.
UVA breast cancer research presentations included the work of Janes Lab MD-PhD candidate Rusty Hawes and Biomedical Engineering undergraduate Alice Chang on a CSBC cross-consortium project. The pair classified cell-state changes in premalignant ductal carcinoma in situ cases treated at UVA, improving understanding of cell expression states in these breast precancers.
Associate Professor of Public Health Sciences Aakrosh Ratan, PhD, shared findings from a supplement project examining the molecular and biological mechanisms underlying racial disparities in breast cancer, which has 40 percent higher mortality for Black women. SASCO’s breast cancer project seeks to identify treatments for highly aneuploid tumors, and work by Dr. Ratan’s team could determine whether those treatments could benefit a higher percentage of black patients.
Breast cancer project team member Catalina Alvarez, a biomedical engineering PhD candidate in the Janes Lab, presented “A Physico-Chemical Theory for the Chromosome Passenger Complex” – a complete computer model for how chromosomes tell cells they are ready to divide.
Dr. Janes shared program highlights from SASCO’s fourth year, including seven publications and three preprints, as well as career advancements: former postdoctoral researcher Sarah Groves is now an Assistant Professor in the School of Data Science, and former predoctoral researcher Sarah Lee is a Senior Scientist with AbbVie pharmaceuticals.
The day culminated in a research poster session and awards with first-place winners, by group:
- Undergraduate Devora Slodowitz of Texas A&M University, embedding in the Janes Lab: “Optimizing the Single-Cell Segmentation and Quality Control Pipeline for Highly Multiplexed Prealignment Breast Tissue”
- Biomedical Engineering PhD candidate William Shao of Jason Papin, PhD’s lab: “Automated Curation of Human Metabolic Gene-Reaction Annotations Using Large Language Models
- Postdoctoral researcher Zuping Wang, PhD, of the Lazzara Lab: “Markov Chain Monte Carlo-Based Parameter Estimation in a Moving Boundary Model of Epidermal Growth Factor Receptor Trafficking”
- Senior Laboratory Specialist Jen Kashatus of the Kashatus Lab: “Unequal Enzyme Distribution in Fragmented Mitochondria Creates Vulnerabilities in Colorectal Cancer Cells.”