Klaus Michael Hahn is an American scientist and educator, recognized for his work developing methods to study molecular behavior inside living cells, especially fluorescent biosensors, optogenetics and chemogenetics.

Education and academic career Hahn earned his B.S in biochemistry and philosophy from the University of Pennsylvania, and his Ph.D. in chemistry from the University of Virginia. After postdoctoral training at Carnegie Mellon University and the Scripps Research Institute, he became an associate professor at Scripps in the Cell Biology Department. He is currently the Ronald Thurman Distinguished Professor of Pharmacology at the University of North Carolina at Chapel Hill. He was co-founder of the Olympus Imaging Center at UNC, and served on advisory boards for the National Cancer Institute’s Frederick National Laboratory, national funding agencies, and NIH imaging centers.

Awards and recognition Hahn is a Fellow of the American Association for the Advancement of Science and was awarded a Transformative R01 Award and the James Shannon Director’s Award from the National Institutes of Health. Nature Reviews Molecular Cell Biology named his work on fluorescent biosensors one of the “ten breakthroughs of the decade”. In 2019 he was awarded the Pearse Prize of the Royal Microscopy Society.

Notable lectures: Pearse Prize Lecture, Royal Microscopy Society, 2019; ABRF national meeting, 2016; Leica Scientific Forum France 2012; Korean Society for Biochemistry and Molecular Biology 2010; International Conference of Systems Biology 2009; Annual Meeting of the Japanese Biochemical Society 2003

Research Hahn has spent his career in academic research and education. He initially developed fluorescent biosensors, molecules that report on control mechanisms within living cells. He and his colleagues pioneered early biosensor designs, including the use of fluorescence resonance energy transfer Kraynov, V. S., C. E. Chamberlain, G. M. Bokoch, M. A. Schwartz, S. Slabaugh and K.M. Hahn. Localized Rac Activation Dynamics Visualized in Living Cells. Science, 290:333-337, 2000.Pertz, O., Hodgson, L., Klemke, R., and Hahn, K.M. Spatio-temporal dynamics of RhoA activity in migrating cells. Nature, 440:1069-1072, 2006. and environment-sensing dyes.Toutchkine, A., Kraynov, V. and Hahn, K.M. Solvent-sensitive dyes to report protein conformational changes in living cells. J. Am. Chem. Soc., 125: 4132-4145, 2003.Nalbant, P., L. Hodgson, V. Kraynov, A. Toutchkine, K. M. Hahn. Activation of Endogenous Cdc42 Visualized in Living Cells. Science, 305:1615-1619, 2004. His laboratory has extended biosensor imaging to study conformational changes of single molecules inside living cells.Machacek, M., Hodson, L., Welch, C., Elliot, H., Pertz, O., Nalbant, P., Abell, A., Johnson, G., Hahn, K.M.* and Danuser, G.* Coordination of Rho GTPase activities during cell protrusion. Nature, 461: 99-103, 2009. PMC2885353 These studies revealed how localized, transient protein activation events, especially of small GTPases, generate cell movement.Liu, B., Stone, O.J., Pablo, M., Herron, C.J., Nogueira, A.T., Dagliyan, O., Grimm, J.B., Lavis, L.D., Elston, T.C., and Hahn, K.M. Biosensors based on peptide exposure show single molecule conformations in live cells. Cell, 184(22): 5670-5685, 2021. PMC8556369Marston, D.J., Vilela, M., Huh, J., Ren, J., Azoitei, M., Glekas, G., Danuser, G., Sondek, J., and Hahn, K.M. Multiplexed GTPase and GEF biosensor imaging enables network connectivity analysis. Nature Chem. Biol., 16(8): 826-833, 2020. PMC7388658

More recently, the Hahn lab focused on precisely controlling specific cell components within cells and animals. They showed how proteins can be engineered to respond to light Wu, Y, Frey, D., Lungu, O. I., Jaehrig, A., Schlichting, I., Kuhlman, B. and Hahn, K.M. Genetically-encoded photoactivatable Rac reveals spatiotemporal coordination of Rac and Rho during cell motility. Nature, 461: 104-110, 2009. PMC2766670Wang, H., Vilela, M., Winkler, A., Tarnawski, T., Schlichting, I., Yumerefendi, H., Kuhlman, B., Liu, R., Danuser, G., and Hahn, K.M. LOVTRAP, An Optogenetic System for Photo-induced Protein Dissociation. Nature Methods, 13(9): 755-8, 2016. PMC5137947Dagliyan, O., Tarnawski, M., Chu, P-H., Shirvanyants, D., Schlichting, I., Dokholyan, N.V., and Hahn, K.M. Engineering extrinsic disorder to control protein activity in living cells. Science. 354(6318):1441-1444, 2016. PMC5362825Stone, O.J., Pankow, N., Liu, B., Sharma, V.P., Eddy, R.J., Wang, H., Putz, A.T., Teets, F.D., Kuhlman, B., *Condeelis, J.S., and *Hahn, K.M. Optogenetic control of Cofilin and aTAT in living cells using Z-lock. Nature Chem. Biol., 15: 1183-1190, 2019. PMC6873228Dagliyan, O., Tarnawski, M., Chu, P-H., Shirvanyants, D., Schlichting, I., *Dokholyan, N.V. and *Hahn, K.M. Engineering extrinsic disorder to control protein activity in living cells. Science, 354: 1441-1444, 2016. PMC5362825 or small molecules,Karginov, A., Ding, F., Kota, P., Dokholyan, N.V., and Hahn, K.M. Engineered allosteric activation of kinases in living cells. Nature Biotech., 28(7): 743-7, 2010. PMC2902629Dagliyan, O., Shirvanyants, D., Karginov, A.V., Ding, F., Fee, L., Chandrasekaran, S.N., Freisinger, C.M., Smolen, G.A., Huttenlocher, A., *Hahn, K.M. and *Dokholyan, N.V. Rational design of a ligand-controlled protein conformational switch. Proc. Natl. Acad. Sci. U.S.A., 110(17): 6800-6804, 2013. PMC3637791Karginov, A., Tsygankov, D., Berginski, M., Chu, P-H., Trudeau, E., Yi, J.J., Gomez, Shawn, Elston, T.C. and Hahn, K.M. Dissecting motility signaling through activation of specific Src-effector complexes. Nat. Chem. Bio. 10(4):286-90, 2014. PMC4064790 using a variety of generalizable techniques. This was especially valuable for the broad range of proteins that, unlike rhodopsins and channel proteins used earlier, had not evolved to respond to light. By inserting engineered domains into specific cell constituents, they and their collaborators elucidated mechanisms of memory,Hayashi-Takagi, A., Yagishita, S., Nakamura, M., Shirai, F., Wu, Y.I., Loshbaugh, A.L., Kuhlman, B., Hahn, K.M., and Kasai, H. Labelling and optical erasure of synaptic memory traces in the motor cortex. Nature 525:333-338, 2015. PMC4634641. immune function,Yoo, S.K., Deng, Q., Cavnar, P.J., Wu, Y.I., Hahn, K.M. and Huttenlocher, A. Differential regulation of protrusion and polarity by PI(3)K during neutrophil motility in live zebrafish. Dev. Cell, 18: 226-236, 2010. PMC2824622Koivusalo, M., Welch, C., Hayashi, H., Scott, C.C., Kim, M., Alexander, T., Touret, N., Hahn, K.M. and Grinstein, S. Amiloride inhibits macropinocytosis by lowering submembranous pH and preventing Rac1 and Cdc42 signalling. J. Cell Biol., 188: 547-563, 2010. PMC2828922 cell motility Wang, X., He, L., Wu, Y., Hahn, K.M. and Montell, D. Light-mediated activation reveals a key role for Rac in collective guidance of cell movement in vivo. Nature Cell Biol., 12(6): 591-597, 2010. PMC2929827 and others.

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