Arne Gennerich, Ph.D.

The Gennerich Lab investigates the molecular mechanisms by which biomolecular motors generate force and motion in eukaryotic cells. We focus on understanding how defects in these processes contribute to human disease. Our research combines single-molecule biophysics, molecular biology, and biochemistry to study the function and regulation of microtubule-based motors—kinesins and cytoplasmic dynein—as well as RNA polymerase II during transcription elongation through chromatin.

Using a multidisciplinary approach that includes high-resolution optical trapping, single-molecule fluorescence microscopy, and CRISPR-Cas9-based genetic tools, we dissect how these motor proteins convert chemical energy into mechanical work and how their activity is modulated in different cellular contexts. Our long-term goal is to uncover the design principles of biomolecular motors and to elucidate the molecular basis of diseases caused by impaired motor function.

Shatarupa A.*, L. Rao*, A. B. Asenjo, A. Gennerich^#, and H. Sosa^#. Pathogenic KIF1A R350 mutations disrupt a conserved and conformation-dependent kinesin-tubulin salt bridge. 2026. Nat. Commun.17:5175 (bioRxiv 2025.08.30.673262) (*: co-first authors; ^#: corresponding authors).

Rao L.*, X. Liu, M. Arnold, R. McKenney, K. Stengel, S. Sidoli, F. Berger, and A. Gennerich*. Adaptor-mediated recruitment of three dyneins to dynactin enhances force generation. 2026. Nat. Cell Biol.28:480-491 (bioRxiv 2025.01.14.632505) (*: corresponding authors)

Rao L., W. Li, Y. Shen, W. Chung^#, and A. Gennerich^#. Distinct Clinical Phenotypes in KIF1A-Associated Neurological Disorders Result from Different Amino Acid Substitutions at the Same Residue in KIF1A. 2025. Biomolecules 15, 656 (bioRxiv 2025.02.26.640415) (^#: corresponding authors)

Liu. X*., L. Rao*, W. Qiu, F. Berger^#, A. Gennerich^#. Kinesin-14 HSET and KlpA are non-processive microtubule motors with load-dependent power strokes. 2024. Nat. Commun. 3:6564 (bioRxiv 2023.06.09.544415) (*: co-first authors; ^#: corresponding authors).

Benoit, M. P. M. H*., L. Rao*, A. B. Asenjo, A. Gennerich^#, and H. Sosa^#. Cryo-EM Unveils Kinesin KIF1A Processivity Mechanism and the Impact of its Pathogenic Variant P305L. 2024. Nat. Commun. 15:5530 (bioRxiv 2023.02.02.526913) (*: co-first authors; ^#: corresponding authors).

Rao^#, L., and A. Gennerich^#. Structure and Function of Dynein's Non-Catalytic Subunits. 2024. Cells, 13:330. (^#: corresponding authors)

Fu, X*,^#, L. Rao*, P. Li, X. Liu, Q. Wang, A. I. Son, A. Gennerich^#, J. S.-H. Liu^#. Doublecortin and JIP3 are neural-specific counteracting regulators of dynein-mediated retrograde trafficking. 2022. eLife, e82218 (bioRxiv 2022.08.10.503449) (*: co-first authors; ^#: corresponding authors).

Pant, D.C.*, J. Parameswaran*, L. Rao L, L. Shi, G. Chilukuri, Z. McEachin, G. Bassell, S. Atienzar-Saez, B. Traynor, J. Glass, A. Gennerich, J. Jiang. ALS-linked KIF5A Δexon27 mutant causes neuronal toxicity through gain of function. 2022. EMBO Rep., e54234 (*: co-first authors)

Impastato, A.C.*, A. Shemet*, N. Vepřek, G. Saper, L. Rao, H. Hess, A. Gennerich^#, D. Trauner^#. Optical control of mitosis with photoswitchable Eg5 inhibitor. 2022. Angew. Chem. Int. Ed., 61:e202115846 (*: co-first authors; ^#: corresponding authors).

Lam, A. J., L. Rao, Y. Anazawa, K. Okada, K. Chiba, S. Niwa, A. Gennerich*, D. W. Nowakowski*, R. J. McKenney*. A highly conserved 310 helix within the kinesin motor domain is critical for kinesin function and human health. 2021. Sci. Adv. 7:eabf1002 (*: corresponding authors)

Boyle, L., L. Rao, S. Kaur, X. Fan, C. Mebane, L. Hamm, A. Thornton, J. T. Ahrendsen, M. P. Anderson, J. Christodoulou, A. Gennerich, Y. Shen, W. K. Chung. Genotype and Defects in Microtubule-Based Motility Correlate with Clinical Severity in KIF1A Associated Neurological Disorder. 2021. HGG Adv. 2:100026.

Budaitis, B. G.*, S. Jariwala*, L. Rao*, Y. Yue, D. Sept^#, K. J. Verhey^#, A. Gennerich^#. Pathogenic Mutations in the Kinesin-3 Motor KIF1A Diminish Force Generation and Movement Through Allosteric Mechanisms. 2021. J. Cell Biol. 220:e202004227 (*: co-first authors listed alphabetically; ^#: corresponding authors). 

Liu, X., L. Rao, and A. Gennerich. The regulatory function of the AAA4 ATPase domain of cytoplasmic dynein. 2020. Nat. Commun. 11:5952 (bioRxiv 2020.09.20.305243)

Brenner, S., F. Berger, L. Rao, M. P. Nicholas, and A. Gennerich. Force production of human cytoplasmic dynein is limited by its processivity. 2020. Sci. Adv. 6:eaaz4295.

Rao, L., F. Berger, M. P. Nicholas, and A. Gennerich. Molecular mechanism of cytoplasmic dynein tension sensing. 2019. Nat. Commun.10:3332. 

Nicholas, M. P., F. Berger, L. Rao, S. Brenner, C. Cho, and A. Gennerich. Cytoplasmic dynein regulates its attachment to microtubules via nucleotide state-switched mechanosensing at multiple AAA domains. 2015. PNAS12:6371-6376. 

Nicholas, M. P.*, P. Höök*, S. Brenner, C. Lazar, R. B. Vallee^#, and A. Gennerich^#. Control of cytoplasmic dynein force production and processivity by its C-terminal domain. 2015. Nat. Commun.6:6206 (*: co-first authors; ^#: corresponding authors). 

Gennerich, A. Molecular Motors: DNA Takes Control. 2014. Nat. Nanotechnol. 9:11-12.