Research

Overview of research program:

How does a single set of genetic instructions give rise to hundreds of different cell types, each behaving in unique ways? And how do those behaviors go wrong in diseases like cancer? Our lab studies the molecular mechanisms that connect a cell's identity to its behavior – with a particular interest in understanding how cells that receive the same signals can end up doing completely different things.

Some of the broad questions driving this work include:

Transcription factors are proteins that act like molecular switches, turning genes on or off. How does the same transcription factor produce different outcomes depending on which cell it's in?
Proteins have functions that can be tuned by where they are located within a cell and which other proteins they associate with. How do these factors influence what a transcription factor actually does?
As an organism develops, cells must both divide to produce more cells and specialize into distinct types with unique jobs. How do these two processes – division and specialization – influence each other?
Cells are constantly receiving signals from their environment, but neighboring cells often respond to the same signal in completely different ways. How does a cell's identity shape the way it "reads" incoming messages?
Answering biological questions requires good tools. How can we build better ways to manipulate protein levels and locations – in living cells, in real time – to understand what they do?

Predoctoral research

As a Ph.D. student in Dr. David Matus’s lab at Stony Brook University, I investigated how conserved invasive programs [Medwig-Kinney & Matus, 2017] are transcriptionally regulated in the C. elegans anchor cell, a specialized uterine cell that invades to create a passage for egg-laying. I dissected the gene regulatory networks controlling anchor cell fate and invasion. Using CRISPR-tagged alleles and RNA interference (RNAi), I revealed previously undescribed roles for two pro-invasive transcription factors in cell cycle regulation [Medwig-Kinney* & Smith* et al., 2020]. These factors initially act in parallel with another pro-invasive transcription factor, NHR-67, to regulate anchor cell fate specification, but later form a feed-forward loop promoting cell cycle arrest and invasion, demonstrating how transcriptional networks can be dynamically rewired during development. I contributed to studies extending this network to other cell types [Yee et al., 2024] and identifying links to chromatin modifiers [Medwig-Kinney & Palmisano et al., 2021, Smith et al., 2022]. I then investigated how invasive and non-invasive states are maintained, tracking cell fate using tools to visualize Notch signaling [Medwig-Kinney et al., 2022, Pani et al., 2022]. I discovered that the default invasive state is actively suppressed – not only through transcriptional downregulation of nhr-67, but also via interactions between residual NHR-67 protein and the C. elegans ortholog of Groucho – revealing a role for transcriptional co-repressors in reinforcing fate [Medwig-Kinney et al., 2023].

Invasion of the anchor cell (magenta) through the basement membrane (green) during development of the reproductive system

Postdoctoral research

I joined Dr. Bob Goldstein’s lab at UNC Chapel Hill to study the cell biological mechanisms driving cell behavior. My research investigates how force-generating machinery is positioned to change cell shape, focusing on apical constriction of C. elegans endoderm precursor cells during gastrulation. I co-led a study using quantitative imaging of endogenously tagged proteins to define the actomyosin architecture underlying this process. We found that myosin and its activating kinase are broadly distributed across the apical cortex, and actin filaments lack radial polarization – distinct from patterns seen in Drosophila gastrulation [Zhang*, Medwig-Kinney* & Goldstein, 2023]. These findings reveal architectural diversity in conserved morphogenetic programs. Building on this work, I have contributed to studies of how actin regulation contributes to apical constriction [Zhang et al., 2024]. In parallel, my undergraduate mentees and I have been investigating how a broadly expressed myosin activator becomes apically enriched specifically in internalizing cells, using a transcriptomics-informed genetic screen to uncover regulators of its localization.

Internalization of endoderm precursor cells (magenta) during C. elegans embryogenesis

Tools and methods development

I have also contributed toward the development of tools and techniques. My collaborative efforts include optimizing techniques for live-cell imaging with lattice light sheet microscopy [Liu et al., 2018], C. elegans microinjection [Gibney et al., 2023], transcription factor profiling [Yee et al., preprint], and visualizing cell cycle state live [Adikes, Kohrman & Martinez et al., 2020]. I also helped with efforts to refine the auxin-inducible degron system by characterizing a water-soluble auxin analog for microfluidics [Martinez et al., 2020], generating cell- and tissue-specific TIR1 drivers [Ashley et al., 2021], and mitigating auxin-independent degradation [Hills-Muckey et al., 2022]. Together, these efforts have helped me establish both a foundation of technical resources and a collaborative network to draw from.

We are grateful to the following organizations for funding and support:

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