My Research Interests

How do epithelia develop and maintain shape? A) Epithelia are composed of mostly identical cells that form sheets. Cartoon shows a classic simple columnar epithelial monolayer. B) Histological image of simple columar human gall bladder epithelium stained with hematoxylin-eosin showing the apical-basal axis of epithelia, which has been largely understudied due to technical limitations. Source: Atlas of plant and animal histology. C and D) Our approach to study epithelial shape using experiments, analysis and modelling in MDCK mammalian cultured cells. We study both the tissue- and the apical-basal- plane of the tissue. These 2 approaches allow us to study of epithelial cell behaviors in four dimensions: three spatial dimensions, through time.

My broad research interest is the effect of physical force and topology on the behavior of cells in the context of tissues.

I am particularly interested in how tissue-level, cell extrinsic forces affect the behavior of cells during tissue remodeling. My work so far has focused on these questions in a developmental context, using the fruit fly Drosophila melanogaster as a convenient model system.

I received my PhD training from the University of Cambridge, UK in 2018 under the supervision of Dr Bénédicte Sanson. My PhD work focused on the morphogenetic movements of Drosophila early embryogenesis. I discovered that vertices (points where 3 of more cells meet) are unique sites of high junctional tension, and that the remodeling of these sites is distinct from that of bicellular cell junctions (Finegan and Hervieux et al. PLoS Biology, 2019). Defects in the remodeling of vertices results in topological changes in tissue architecture in response to the extrinsic forces imposed by neighboring tissues.

 My postdoctoral work at the University of Rochester has addressed questions concerning the remodeling of an epithelial monolayer in the Drosophila ovary. I discovered that cells in this tissue break a fundamental law of cell biology- their shape does not determine their division orientation (Hertwig’s law, 1884). Instead, the orientation of cell division is determined by tissue-level tension. (Finegan et al. EMBO J, 2019 and review article Finegan and Bergstralh Cell Cycle, 2019). I also determined the molecular mechanism by which cells can incorporate into a tissue layer following misplacement due to misoriented divisions (Cammarota and Finegan et al Current Biology, 2020).

My work stands out because it bridges biological scales- I have investigated the role and behavior of subcellular biological units (proteins), tracked the behavior of individual cells, and quantified tissue shape and remodeling to address my research questions. My research is also unique in the context of the field because it addresses the remodeling of tissues in 3 dimensions and has revealed novel roles for non-cadherin-based cell adhesion complexes in tissue morphogenesis, which have been previously overlooked (Finegan and Bergstralh Phil Trans R Soc London B Biol Science 2020).

My Postdoctoral Work

I spent one year receiving postdoctoral training at Syracuse University with J.M. Schwarz and M. Lisa Manning in computational modelling and quantitative methods. I worked on a project to investigate how tissue shape and rheology influences metastatic potential. I developed a Python-based vertex model code base (Sansivieria). The manuscript from this work remains in progress.

For cancer to metastasize, i.e. spread to other parts of the body, cancer cells must first escape from a localized tumor and invade their surroundings. Cancer cells exhibit myriad invasion strategies that are challenging to predict in vivo. Therefore, this phenomenon is studied in vitro using tumor spheroids, multi-cellular aggregates embedded in a collagen matrix. To determine how the geometry and the rheology of the spheroid affects how cells escape a tumor,  we are constructing and studying a minimal computational model in two dimensions for the outer edge of a spheroid that allows us to connect larger-scale geometric and rheological properties of the spheroid to the shapes of individual cells. We are testing the hypothesis that rigid spheroids undergo brittle, single cell break-out, whereas more fluid spheroids exhibit more ductile, multi-cell break-out to allow us to formulate experimentally-testable predictions for the metastatic potential of spheroids and, ultimately, cancerous tumors.

My Doctoral Research

In Brief:

I studied how cells in tissues rearrange to drive the building of animal bodies and organs.
Broadly, the questions that I addressed in my doctoral research were:

  • How do cells in epithelial tissues rearrange whilst maintaining adhesion?

  • What are the sub-cellular components that drive junctional rearrangements, and how do they do this?

  • What are the relative contribution of intrinsic and extrinsic mechanisms that drive tissue morphogenesis?

I used the fruit fly Drosophila melanogaster as a model system to study these questions. This is because they share many fundamental physiological and cell biological features with humans, are genetically tractable and easy to image. Find out more about why we use Drosophila in research here.

My PhD Thesis is available online here.

A publication resulting from my doctoral research is found here.