Dissecting Cell Type-Specific Metabolism in Pancreatic Ductal Adenocarcinoma
This week we profile a recent publication in eLife from Allison Lau (pictured) the laboratory of Dr. Matthew Vander Heiden at MIT.
Can you provide a brief overview of your lab’s current research focus?
Our laboratory is working to understand how metabolism supports cell physiology, with a focus on cancer. We are defining how environmental factors impact metabolism at the cell, tissue, and organism level, and identifying aspects of metabolism that are limiting for cell proliferation in different contexts. Our current interests include identifying which products of metabolism create bottlenecks for cell proliferation and understanding how different cancers repurpose metabolism to enable tumor growth. We are also interested in how diet and whole body metabolism influence cell metabolism in tissues to modify cancer and other disease phenotypes. Through our work, we aim to advance understanding of metabolic pathway biochemistry and its relationship to cancer and mammalian physiology.
What is the significance of the findings in this publication?
This work provides new insight into the metabolic differences between cancer and stromal cells in their endogenous microenvironments. Our data suggest that stable isotope tracing into macromolecules can be utilized to deconvolute complex tracing patterns in mammalian tissues, including tumors, to identify increased pathway activity in a particular cell type. Understanding the metabolic similarities and differences between cancer cells and stroma within pancreatic ductal adenocarcinoma and other tumors will be important in further delineating cancer-specific dependencies.
What are the next steps for this research?
This approach can be applied to studying other metabolic pathways in cancer cells and stroma by combining use of multiple different isotope-labeled nutrients and examining isotope-labeling patterns in other stable end products of metabolism including lipids and nucleic acids. These methods can also be expanded for use in studying metabolism in other heterogeneous systems including other types of cancer, metastases, and normal tissues.
This work was funded by:
The first author, Allison Lau, was a Robert Black Fellow of the Damon Runyon Cancer Research Foundation, DRG-2241-15, and is currently supported by a NIH Pathway to Independence Award (K99CA234221).
Matthew Vander Heiden acknowledges support from the Lustgarten Foundation, a Faculty Scholar grant from the Howard Hughes Medical Institute, SU2C a division of the Entertainment Industry Foundation, the MIT Center for Precision Cancer Medicine, the Ludwig Center at MIT, the Emerald Foundation, and the NCI (R01CA168653, R01CA201276, R35CA242379, P30CA14051).