hahn lab

researchsee the contacts page for available positions

Our lab develops novel molecules that report and control protein behavior in vivo. We strive to develop broadly applicable approaches, but this is driven by addressing specific questions about immune cell function and cancer cell trafficking. We have a highly collaborative lab, where we leverage our strengths by interacting with other investigators to combine disparate fields and technical abilities. In technique development, our focus is on protein engineering and novel dyes, used to build proteins that report signaling behavior, or manipulate signaling networks in vivo using light or small molecules. In our biological studies, we focus on dynamic cellular processes, where spatio-temporal control of signaling is critical, and where communication occurs rapidly across many scales in living cells. Students and postdocs in our lab can work anywhere on a continuum from molecular engineering to biological studies. Our friends and collaborators work in the complementary fields of molecular modeling, computational image analysis, network modeling, development of novel microscopes and imaging hardware, or high throughput screening. Here are brief outlines of some current funded projects and new directions we are exploring:

photoactivation of rac with arrowMolecules and microscopes.We have published extensively on fluorescent biosensors, and more recently on controlling  protein function using engineered domains that respond to small molecules or light. This work is the foundation of our biological studies below, as we continue to develop new approaches to quantify, model and manipulate signaling in vivo.  We are synthesizing small molecules that interface with engineered proteins, and dyes to report protein behavior and diagnose disease. We are beginning an exciting new area in which we design molecules and approaches for novel microscopes developed by Eric Betzig and Leong Chew at Janelia Research Institute. (Image: Activation of Rac1 (spot) leads to gradient of Pak activity; Yi Wu, Hahn lab)

biosensorGTPase networks. In several related projects that have been a major focus of our laboratory for years, we are studying the rapid kinetics of GTPase signaling ‘circuits’ and how their transient construction at specific locations controls cell motility. We are focused now on the 'logic' of signaling networks that integrate and relay information from receptors to GTPases, with emphasis on the role of guanine exchange factors.  New approaches for network imaging are used to quantify and control specific protein activities, to understand the interactions of adhesion, cytoskeletal and trafficking systems, and  to decipher mechanisms of cell polarization, directionality and turning. New microscope techniques are helping us quantify signaling kinetics in individual cells with great accuracy for quantitative modeling and a deeper understanding of network architecture. This work involves close collaboration with the labs of John Sondek (UNC), Gaudenz Danuser (Harvard), Tim Elston (UNC), Shawn Gomez (UNC), Keith Burridge (UNC) and Alan Hall (Sloan Kettering). (Image: Biosensor fluctuation analysis reveals GEF/GTPase feedback loops. Hunter Elliot, Danuser lab, Harvard)

Zebrafish and engineered allostric activation. We are working on new tools to examine and control signaling in zebrafish, transparent animals that serve as excellent microscopy models for human disease and development. The bulk of our work on engineered allosteric control of proteins occurs here, using small molecule that can be added to the medium to activate proteins or specific pathways within larger networks. We are also examining how biosensors can be tailored for use in vivo, and exploring novel microscopes and biophysical approaches for deep tissue penetration and quantitative determination of signaling activity in complex environments like living tissues. These projects are being pursued together with Anna Huttenlocher and Kevin Elicieri at U. Wisconsin, studying EMT and neutrophil infiltration of tumors.

Transendothelial migration. Cells signal through adhesion molecules endothelial cupon blood vessel walls to pass through the blood vessels for immune surveillance, cancer metastasis and a host of other processes important in homeostasis and disease. Little is known about how the adhesion molecules coordinate synchronized changes in the cytoskeletons of the blood vessel endothelial cells and the transmigrating cells. We are using correlation and lifetime imaging, together with new techniques for examining multiple biosensors simultaneously, to probe the signaling that guides transendothelial migration. Using 3D force microscopy developed by our collaborator, Richard Superfine, we are asking how physiologically relevant forces affect adhesion molecule signaling to Rho family GTPases. We are working closely with the labs of Claire Doerschuck (UNC) and Keith Burridge (UNC). (Image: Leucocytes induce cups in endothelial cells; Jaap Schroeder, Burridge Lab, UNC)


Thanks to our collaborators for sharing their enthusiasm and for making exciting science possible. Here are the web sites of some of our current 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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