Hahn Lab News

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04/2013 - Congratulations to Chris MacNevin (at right in picture), who placed second for his research poster entitled "The small molecule based biosensor CaMbio reports calmodulin activation dynamics in cells and in vivo." The 3rd Annual Oliver Smithies Nobel Symposium Postdoctoral Research Poster Forum was held Friday, April 19 at UNC. The forum provides an opportunity for fellows to hear inspiring stories presented by previous Nobel Prize winners and to highlight their current research. The poster presentations followed the keynote speech by Dr. Harold E. Varmus.
04/2013 - Denis Tsygankov was invited to give a platform talk on “Dissecting kinase-mediated pathways with temporal and spatial control of their activation” at the Moscow Conference on Computational Molecular Biology.
04/2013 - Welcome to Andrey Krokhotin, who just joined our lab and the lab of Nikolay Dokholyan to work on our collaborative project controlling Rho family GTPase networks with light.
02/2013 - Onur Dagliyan and Hui Wang presented platform talks at the Annual Meeting of the Biophysical Society, Onur on “Rational design of protein conformational switch”, and Hui on “LOV-TRAP: A broadly applicable, genetically encoded system to control protein activity with light through controlled sequestration at membranes.”
12/2012- Hui Wang and Andrei Karginov are invited to speak at the 2012 American Society for Cell Biology meeting, describing their work on photomanipulation, and engineered allosteric control of proteins in living cells.
10/2012- Amy Hsu becomes Dr. Hsu - an impressive and amazing transformation on Halloween. Amy is leaving for her new haunts at the NIH.
8/2012- Onur Dagliyan has been awarded an MCC Travel Grant of $1000 to attend "Exploring Protein Interactions through Theory and Experiements" on 2012-09-24.
8/2012- Onur Dagliyan wins a Howard Hughes International Research Fellowship to work on new methods to control protein activity in vivo using engineered allosteric regulation. Congratulations to Onur!
7/2012- Goodbye and much luck to Janet Doolittle, who just struck a triple play. Within one month she received the American Heart Association Predoctoral Fellowship, graduated with her PhD, and was awarded a postdoctoral fellowship from the NextGen Oral Health program at UNC. She will be studying viral pathogenesis in the laboratory of Dr. Webster-Cyriaque.
7/2012- Klaus and Anna Huttenlocher of U. Wisc., Madison receive a multiPI grant from the NIH to develop a live cell imaging ‘toolchest’ for zebrafish research, focusing on photomanipulation, engineered allosteric activation and biosensors in studies of EMT.
7/2012- Klaus, Claire Doerschuck and Keith Burridge receive a multiPI grant from the NIH to study transendothelial migration in animals using multiplexed biosensors and Rho family photoactivation.
6/2012- Congratulations to Jason Yi, invited to lecture at the 36th meeting of the American Society for Photobiology in Montreal, Canada, on techniques for controlling cell physiology with light.
6/2012- Scott Slattery receives American Heart Association fellowship to study the role of the cytoskeleton in transendothelial migration. Scott will be developing new approaches to control one signaling molecule while monitoring another in vivo.
5/2012- Farewell to Andrei and congratulations. Good luck as a new Assistant Professor at the U. of Illinois - Chicago.
3/2012- Klaus is selected by the medical students to present their Pharmacology review lecture for the national boards.
4/2012- Best wishes and congratulations to Richard Allen, who is joining Pfizer in Cambridge as a senior scientist.
4/2012- Our work with light-activated proteins is highlighted in an article in Nature Methods on "Direct protein control."
2/2012 - Klaus is funded by the Autism Speaks foundation to pursue our discovery of signaling pathways underlying autism.
2/2012- Congratulations to Jason Yi, who received an NIH Ruth L. Kirschstein postdoctoral fellowship for his proposal examining the role of protein dynamics in autism.
12/2011- Congratulations to Oana Lungu for becoming a Doctor! Oana is on her way to U. Texas–Austin Chemical Engineering Dept. for postdoctoral studies with George Georgiou.
11/2011- Pei-Hsuan Chu wins first place in the poster contest at our Pharmacology annual retreat. Her poster describes the role different Src isoforms play in cell motility, and activation and inhibition of Src isoforms with light.
9/2011- We make the cover of Nature Reviews Molecular Cell Biology for our review article on imaging multiple signaling activities in living cells, by Chris Welch, Hunter Elliott, Gaudenz Danuser and Klaus.
7/2011- Chris Welch receives his PhD for his work studying the control of cell polarity by GTPase trafficking. He is given a ‘high pass’, a rare distinction at UNC. Chris is returning to UNC Med for the clinical portion of his MD/PhD training.
7/2011- Welcome to Onur Dagliyan who is joining our lab as a grad student. Onur will be jointly mentored by Klaus and Nikolay Dokholyan, applying computational approaches for new methods to quantify endogenous protein activity.
7/2011- Farewell and much happiness to Jianrong Wu, who leaves the lab to become a Research Scientist at Intel in Arizona.
6/2011- Welcome to Li Li who is joining the lab as a postdoc, using FLIM and correlation analysis to examine GTPase trafficking.
6/2011- Congratulations to Hui Wang for receiving an Arthritis Foundation Postdoctoral Fellowship, for studies on transendothelial migration using novel methods to control protein function with light.
6/2011- Congratulations to Ellen O’Shaughnessy for receiving a Lineberger Cancer Center Fellowship to work on quantitative models of cancer signaling in a project bridging our lab, the Elston lab and the Der lab at UNC.
6/2011- Welcome to Ellen O’Shaughnessy who is joining the lab as a postdoctoral fellow to develop quantitative models of signaling pathways regulating cancer motility.
5/2011- Congratulations-Jason Yi is named the Christina Castellana Postdoctoral Fellow of the Foundation of Angelman Syndrome Therapeutics.
2/2011- Congratulations to Christopher Welch who has received the Joseph S. Pagano Award from the Lineberger Cancer Center for his graduate thesis studies, including a $5000 cash prize.
2/2011- Congratulations to Oanu Lungu, invited to give a Young Investigator talk at the Protein Society Annual Meeting, focused on our collaboration with Brian Kuhlman to develop caged peptides using computational modeling of the LOV domain.
1/2011- Congratulations to Andrei Karginov, whose poster on engineered allosteric control of kinases was selected for a presentation at the Keystone Conference “Evolution of Protein Kinases.”
10/2010- Nature Reviews Molecular Cell Biology names our work one of the “Ten breakthroughs of the decade” in their 10th anniversary issue, highlighting our work with biosensors and photoactivatable proteins.
10/2010- Nature Methods highlights our work with rapid allosteric activation.
9/2010- Our lab is funded to work with the NIH Protein Structure Initiative to study “Assembly, dynamics and evolution of cell-cell and cell-matrix adhesions.”
8/2010- Klaus, Haruo Kasai and Brian Kuhlman receive a grant from the Human Frontiers in Science Program to develop “Optogenetics for small G-proteins and protein kinases in neuroscience.”
8/2010- Congratulations to Eric Vitriol, who is taking his new PhD to Emory, where he will be doing postdoctoral work in the Zheng lab.
7/2010- "The Scientist" highlights our work illuminating cell mobility using light to activate Rac proteins.
7/2010- Congratulations to Chris MacNevin on being awarded an American Cancer Society Postdoctoral Fellowship.
7/2010- Farewell and heartfelt wishes for success to Yi Wu as he leaves to become an Assistant Professor at the U. of Conn. Medical School.
7/2010- Congratulations-Jason Yi is Awarded a Fellowship from the Carolina Institute of Developmental Disabilities.
7/2010- Welcome to Scott Slattery who is joining the lab as a postdoc. Scott will work on high throughput and high content analysis of signaling behavior, and combining photomanipulation and sensing of signaling pathways.
7/2010- Congratulations to Akash Gulyani who received a UNC Post-Doctoral Mentoring Award for his work with undergraduate students developing new fluorescent dyes.
7/2010- Farewell and much luck to Jon Zawistowski, who is leaving to become a Research Assistant Professor in the Johnson lab here at UNC.
5/2010- Welcome to Janet Doolittle who is joining the lab as a grad student to study transendothelial migration.
5/2010- Welcome to Jason Yi who is joining the lab as a postdoctoral fellow to apply biosensors to pathways important in autism.
5/2010- Yi Wu is invited to present at the “Science at the Interface Symposium”, U. Chicago.
3/2010- Congratulations to Chia-Wen Hsu who presented her work on novel dyes and biosensors for studying endogenous proteins at the 8th International Student Seminar, Kyoto University, Japan.
2/ 2010- Congratulations to Yi Wu, invited to present his work on optogenetics of GTPase proteins at the High Content Analysis meeting, San Francisco.
2/2010- Klaus joins UNC Bioinformatics and Computational Biology curriculum.
2/2010- Klaus is named a Fellow of the American Association for the Advancement of Science.
1/2010- Chia-Wen Hsu visits and presents at the Institute of Biology, Humboldt University, Berlin, Germany.
10/2009- Klaus is awarded an NIH Transformational Roadmap Award with Gaudenz Danuser to study “Quantitative imaging of signaling networks.”
9/2009- We publish back to back papers in Nature! One is with Gaudenz Danuser, developing and applying new methods to study the coordination of multiple GTPases in living cells, and the second demonstrates the control of Rac1 by light in living cells using a new optogenetics approach capable of ‘caging’ cytosolic proteins.
6/2009- Farewell to Professor Jung Weon Lee who returns to Seoul U., Korea, after a 2 year visit to our lab.
5/2009- Congratulations to Christopher Welch, invited to present at the Symposium on Adhesion and Migration in Inflammation.
3/2009- Welcome to Richard Allen who is joining the lab as a postdoc, jointly mentored by Klaus and Tim Elston. Richard is developing new image analysis methods and associated quantitative models of signaling dynamics.
3/2009- Christopher Welch is invited to present at the Annual MD/PhD student conference organized by Keystone and NIGMS.
3/ 2009- We are issued a patent on our live cell biosensor technologies: US 7,592,188.
3/2009- Congratulations to Oana Lungu for her American Heart Association Graduate Student Fellowship, focused on studies of adhesion dynamics using photocontrol of adhesion proteins.
1/2009- Welcome to Chris MacNevin who is joining the lab as a postdoc. Chris will work on development of biosensors for endogenous proteins in a collaboration with Stephen Frye at UNC.
2009- Congratulations to Christopher Welch who has received an NRSA Predoctoral Fellowship Award from the NIH.

research

Our lab is essentially two labs: One is focused on developing new techniques and molecules to study dynamic signaling behaviors in living cells and animals; the other uses these tools to decipher basic biology principles and their roles in cancer and immune surveillance. We are currently focused on cell motility and polarization driven by adhesion, in metastasis and trans-endothelial migration. 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 organic synthesis, used to build novel 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 between pure tool development/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:

GTPase networks. This broad area encompasses multiple related projects that have been a major focus of our laboratory for years. We began by studying GTPase proteins, and now are moving upstream to decipher the ‘logic’ of signaling networks that integrate and relay information from receptors to GTPases to control cell movement. Ultimately we hope to not only elucidate signaling networks, but to engineer cells whose responses and movements can be controlled to serve in the clinic. Network imaging and modeling drive the development of tools to quantify and control specific protein activities, to understand the interactions of adhesion, cytoskeletal and trafficking systems, and currently 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), Enrico Gratton (UC Irvine), 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 on 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)

Molecules 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 an integral part of the biological studies above, and a major focus as we continue to develop new approaches to see and manipulate signaling in vivo. We are also using organic synthesis to build small molecules that interface with engineered proteins, and to synthesize fluorophores for biosensors with valuable new capabilities. Much of this work is made possible by collaborations with Nikolay Dokholyan (UNC), and Brian Kuhlman (UNC), experts in protein modeling and design. We are beginning an exciting new area in which we couple our design of molecules with novel microscopes and biophysical techniques developed by Enrico Gratton at the Laboratory for Fluorescence Dynamics at UC Irvine. (Image: Activation of Rac1 (spot) leads to gradient of Pak activity; Yi Wu, Hahn lab)

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:

hahn lab

Hahn Lab News

research

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: