Michelle Mendoza

The Mendoza lab mission is to help patients with lung cancer and other solid tumors through the discovery of fundamental mechanisms of cancer progression. We apply physical science perspectives to understand biochemical and biomechanical signaling in tumor cells and their microenvironment.

We are interested in the signaling of cell migration and cancer invasion. Questions addressed in the lab include:

• How do signaling pathways synergistically control actin and adhesion dynamics for cell movement?
• How biomechanical forces cooperate with ERK signaling to drive lung cancer invasion?
• How do activated fibroblasts communicate with tumor cells to promote cancer progression?

We approach these and other biological problems with a combination of experimental and computational techniques, including biochemistry, quantitative imaging, simulations, and mouse models. Students in the lab receive interdisciplinary training spanning cancer biology, biomechanics, and translational science through collaborations across Huntsman Cancer Institute and the University of Utah

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Cell migration requires coordinated regulation of actin assembly, adhesion dynamics, and force generation. We investigate how signaling pathways integrate these processes to direct cell movement, and how this is activated during cancer invasion.

Integrated Forces for Cell Migration
How do cells convert signaling information into physical movement? Our laboratory investigates the molecular and mechanical mechanisms that power cell migration. We have shown that ERK signaling coordinates actin assembly, adhesion dynamics, and cellular contractility to generate productive movement. Current projects explore how these forces are integrated across cells and their surrounding extracellular matrix, providing new insight into both normal cell behavior and the invasive migration of cancer cells.

Tumor Biomechanics and Cancer Invasion
When cancers spread throughout the body, tumor cells navigate altered tumor microenvironments and foreign structures. A computational modeling collaboration with the Weiss lab in Biomedical Engineering showed that tensile strain can be amplified at the edge of early lung tumors and in the tumor microenvironment. We are characterizing the roles of strain signaling in early lung tumors by experimentally stretching tumor cells and tumor-associated fibroblasts. With continued modeling, we are identifying mechanisms by which the altered mechanical forces promote tumor invasion.

Lung Cancer Progression
Our lung cancer research also seeks to understand how environmental exposures interact with genetic mutations to drive disease progression. We study how toxic exposures and tissue injury promote fibroblast activation, extracellular matrix remodeling, and tumor progression. Students in the lab use a combination of mouse models, human tissue, quantitative imaging, and collaborations with population scientists to understand how these interactions cause aggressive lung cancer phenotypes and resistance to therapeutics.