hahn lab

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Our lab focuses on two synergistic areas: development of proteins and small molecules to visualize and control protein activity in live cells and animals, and applying these tools to address basic questions re spatio-temporal control of signaling. Our biological studies center on the role of cytoskeletal and adhesion dynamics in signaling crosstalk, directed motility, and the role of immune cells in disease. We are extending our cell biology studies to examine metastasis and macrophage motility in 3D models and in vivo.

While addressing specific molecules for our biological studies, we have produced generally applicable approaches to visualize and control signaling. These include new fluorescent biosensor designs to quantify conformational changes of endogenous proteins, and biosensors based on engineered protein scaffolds for otherwise inaccessible molecules. We are developing fluorescent dyes for single molecule microscopy of protein conformational changes in vivo, and engineered domains that can be inserted into target proteins to control protein function using either light or small molecules. Other new methods selectively activate specific protein behaviors.

We greatly benefit from interactions with collaborators who focus on computational image analysis, modeling of signaling dynamics, and developing novel microscopes.


Ongoing research directions in our laboratory:

See publications for complete list of references.

Rac1 FLARE biosensor reveals dynamics of Rac activation in protrusions
Rac1 FLARE biosensor reveals dynamics of Rac activation in protrusions; Chris Welch

Fluorescent biosensors. We are working on multiple facets of biosensor technology for quantitative visualization of protein activity (conformational change, post-translational modification, ligand interactions etc) in living cells and animals;   We are pursuing multiplexed imaging (for protein visualization and control), novel modes of detection and quantitation, FRET, affinity reagents, novel dyes to report endogenous protein activity, and high content screening of engineered scaffolds for access to otherwise inaccessible targets.

UniRapR domain confers drug sensitivity on kinases in vivo
UniRapR domain confers drug sensitivity on kinases in vivo; Onur Daglilyan
Engineering proteins to confer regulation by light or by small molecules. Our goal is to produce broadly applicable approaches that can inhibit or activate proteins of many different families with either light or small molecules. By controlling protein activity at precise times and places within cells we probe the role of activation dynamics in cellular ‘decision making’.  This is based on understanding allosteric networks, high content screening, and analysis of protein structure and dynamics.

Leucocytes induce cups in endothelial cells
Leucocytes induce cups in endothelial cells; Jaap Schroeder, Burridge Lab, UNC
Examining the spatio-temporal dynamics and regulation of Rho family GTPase signaling pathways. How do the cytoskeleton and adhesion complexes produce transient activation events with precise kinetics and location; What role do these play in cell ‘decision making’?  Our own work is now focused on cell behaviors in the tumor microenvironment and on unique functions of blood cells (eg macrophage phagocytosis and megakaryocyte platelet formation). We have been able to help collaborators apply our biosensors and protein manipulation tools to examine other cellular functions, and the physiology of larger organisms.


Dmitriy Gremyachinskiy sheds light on dye chemistry
Dmitriy Gremyachinskiy sheds light on dye chemistry.
Novel dyes to illuminate cell biology and protein behaviors. We are trying to understand the physical basis of dye fluorescence properties, to generate dyes whose fluorescence responds to the environment. The dyes are designed for living cells (bright, long wavelength, photostable) but are also valuable for in vitro biochemical/biophysical applications.  We have used them to report protein conformational changes and protein interactions in vivo and in drug screening applications. We are now focused on making dye-based biosensors more practical by coupling dyes to proteins inside living cells etc.

Biosensor fluctuation analysis reveals GEF/GTPase feedback loops. Hunter Elliot, Danuser lab, Harvard
Biosensor fluctuation analysis reveals GEF/GTPase feedback loops. Hunter Elliot, Danuser lab, Harvard
Quantitative microscopy and analysis of signaling circuits / systems biology. We interact with other labs who push the limits of imaging technology. We produce biosensors and protein manipulation tools to take advantage of novel microscopes, and collaborate closely with several groups to develop image analysis methods and quantitative models to understand the 3D/rapid signaling we are studying.

Thanks to our collaborators!

Thanks to the following organizations,  and to the US and NC taxpayers,  for their support:

NIH logo American Cancer Society logoNational Heart Assn logo
The Leukemia Lymphoma Society logoArthritis Foundation LogoCell Migration Consortium logo
US Dept. of Defense LogoDeutche Forschungsgemeinschaft logo
UNC CIDD logoUniversity Cancer Research Fund logo
NIDKK logo Autism Speaks logo Terran funding logo


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