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Christy Heidema

Mentor: Kris A. DeMali, PhD

Year Entered Into Program: 2014

PhD Institution: University of Iowa, 2018

Affiliations

  • Molecular Medicine

Research Description

The role of cell stiffening in cancer metabolism

All cells are subjected to mechanical forces throughout their lifetimes. These forces are sensed by cell surface adhesion receptors, known as integrins and cadherins. Upon sensing force, adhesion receptors trigger robust actin cytoskeletal rearrangements and prompt growth of the associated adhesion complex. This process is called reinforcement or cell stiffening. The ability of a cell to modulate its stiffness is critical for maintaining a balance of forces between the cell and its environment. Imbalances underlie the etiology and progression of many diseases, including cancer, hypertension, and cardiovascular disease. In particular, alterations in cell stiffness modify how cells grow and migrate. These events have been best studied in cancer, where alterations in cell stiffness can promote tumor growth and metastasis. 

In response to force, adhesion receptors increase intracellular enzymatic activities, actin polymerization, and actomyosin contractility. These events support cytoskeletal rearrangements and growth of the adhesion complex needed for cell stiffening. However, each of these processes requires energy. Where cells derive the necessary energy to support cytoskeletal rearrangements that enable cell stiffening remains an unanswered question and is the focus of my research. To address this research question, we have two goals: (1) to determine the energy source for cytoskeletal changes that occur when cadherins experience force and (2) to identify the physiological relevance of cell stiffening in mouse models of breast cancer.

Awards

  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2016-2017
  • Institutional support on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2015-2016
  • Presidential Graduate Research Fellowship, 2014-present

Publications

  1. Bays, J.L., Campbell H.K., Heidema, C., Sebbagh, M. and K.A. DeMali, K.A.:  Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK.  Nat. Cell Biol. 19(6):724-731, 2017.  PMCID: PMC5494977

Research