Ph.D. Chemistry, Wayne State University

Single-molecule methods are powerful techniques to study complex and diverse biological processes because of their capability to provide detailed information about molecular mechanisms, which are hidden in conventional ensemble experiments. The long-term goal of my research is to make significant contributions to understanding how complex biological entities and interactions take place at the molecular level. Understanding how the dynamic interactions between biomolecules control their assembly pathway will help us to predict potential defects in such processes caused by different diseases. Detailed information on biomolecular assembly pathways will ultimately guide us towards the design and development of therapeutics targeting each step of assembly.

Research in my lab focuses on the application and advancement of single-molecule fluorescence in the study of conformational dynamics and activation mechanism of G protein-coupled receptors. We are also interested in real-time visualization of trafficking of HIV-1 RNA (RRE) in the cellular environment.

Agyemang, E., Gonneville, A., Tiruvadi-Krishnan, S., and Lamichhane, R., Exploring GPCR conformational dynamics using single-molecule fluorescence. Methods., 226, 2024, 35-48.

Wei, S., Pour, N.G., Tiruvadi-Krishnan, S., Ray, A.P., Thakur, N., Eddy, M.T., and Lamichhane, R., Single-molecule visualization of human A_2A adenosine receptor activation by a G protein and constitutively activating mutations. Commun Biol., 6, 2023, 1218.

Liu, T., Khanal, S., Hertslet, G.D., Lamichhane, R., Single-molecule analysis reveals that a glucagon-bound extracellular domain of the glucagon receptor is dynamic. J Biol Chem., 2023, 105160.

Thakur, N., Wei, S., Ray, A.P., Lamichhane, R.*, and Eddy, M.T.*, Production of human A_2AAR in lipid nanodiscs for ¹⁹F-NMR and single-molecule fluorescence spectroscopy. STAR Protoc., 2022, 16;3(3):101535.

Wei, S., Thakur, N., Ray, A.P., Beining, J., Obeng, S., McCurdy, C.R., McMahan, L.R., Gutiérrez-de-Terán, Eddy, M.T., and Lamichhane, R. Slow conformational dynamics of the human A_2A adenosine receptor are temporally ordered. Structure, 2021, 30, 329-337.

Lamichhane, R., Liu J.J., White, K.L., Katritch, V., Wüthrich, K., Stevens, R.C., and Millar, D.P. Biased Signaling of the G-Protein-Coupled Receptor β₂AR Is Governed by Conformational Exchange Kinetics. Structure, 2020, 28, 1-7.

Lamichhane, R.* Liu J.J.*, Pljevaljcic, G., van der Schans, E., Katritch, V., Wüthrich, K., Stevens, R.C., and Millar, D.P. Single-molecule view of basal activity and activation mechanisms of the G protein-coupled receptor β₂AR. PNAS, 2015, 112, 14254-59.

Lamichhane, R., Berezhna, S.Y., Gill, P.J., Van der Schans, E., and Millar, D.P. Dynamics of site switching in DNA polymerase I. JACS, 2013, 135, 4735-42.

Lamichhane, R., Solem, A., Black, W., and Rueda, D. Single molecule FRET of nucleic acid-protein and protein-protein interactions: surface passivation and immobilization. Methods, 2010, 52, 192-200.

Lamichhane, R., Daubner, G., Thomas-Crusells, J., Auweter, S.D., Manatchal, C., Austin_, K.S., Vaniuk, O., Allain, F.H., and Rueda, D. RNA looping by PTB: evidence using FRET and NMR spectroscopy and for a role in splicing repression. PNAS, 2010, 107, 4105-10.