Position Title
Associate Professor
- Molecular and Cellular Biology
Research Interests
I have a long-standing research interest in the cytoskeleton, and in particular the motor proteins that utilize the cytoskeleton as tracks for intracellular transport. I was fortunate to have an opportunity at basic research beginning early in my undergraduate career, where I worked on signaling pathways related to cancer. This work afforded me valuable, early experience in the lab, and confirmed to me that I wanted to pursue research as a career. I pursued graduate research focused on the mechanochemical regulation of the microtubule motor cytoplasmic dynein. At Columbia University, I joined the lab of Dr. Richard Vallee, who discovered the motor protein cytoplasmic dynein. My work was the first to describe how two regulatory proteins, LIS1 and NudE, are able to modulate dynein’s motor output, transforming it from a weak to a persistent motor. This work combined biochemistry and biophysical approaches to provide insights into long-standing questions in the dynein and brain development fields, as LIS1 is the causative gene of the neurodevelopmental disease lissencephaly. I then moved to the lab of Dr. Ron Vale at UCSF to continue my studies on dynein using advanced single molecule microscopy. In Ron's lab I have made several contributions to the dynein field, including how dynein organizes microtubule networks, how it is activated and linked to cargo through the dynactin complex and adapter proteins, and how its motor activity is directly influenced by post-translational modification of the microtubule track itself.
My lab is interested in the fascinating world of molecular movement. We study how cells internally organize using molecular motor proteins. In particular, we focus on the microtubule cytoskeleton and the motor proteins that use this filament system for transport (kinesins and dyneins). We are interested in allosteric regulation of motor protein movement, how motor activity is balanced and coordinated, and how dysfunction in motor activity leads to human diseases such as cancer and neurodegeneration. The lab combines advanced molecular biology, biochemistry and single-molecule TIRF microscopy to address these problems.
Graduate Program Affiliations
- 2002 B.S. in Biology, Xavier University
- 2010 Ph.D. in Pathology and Cell Biology, Columbia University
- Chiba K, Ori-McKenney KM, Niwa S, McKenney RJ. Synergistic autoinhibition and activation mechanisms control kinesin-1 motor activity. Cell Rep. 2022 May 31;39(9):110900. doi: 10.1016/j.celrep.2022.110900. PubMed PMID: 35649356; NIHMSID:NIHMS1812260.
- Lam AJ, Rao L, Anazawa Y, Okada K, Chiba K, Dacy M, Niwa S, Gennerich A, Nowakowski DW, McKenney RJ. A highly conserved 310 helix within the kinesin motor domain is critical for kinesin function and human health. Science Advances. 2021 Apr 30;7(18):eabf1002. doi: 10.1126/sciadv.abf1002. PMID: 33931448.
- Sharma A, Preece B, Swann H, Fan X, McKenney RJ, Ori-McKenney KM, Saffarian S, Vershinin MD. Structural stability of SARS-CoV-2 virus like particles degrades with temperature. Biochem Biophys Res Commun. 2021 Jan 1;534:343-346. doi: 10.1016/j.bbrc.2020.11.080. Epub 2020 Nov 28. PMID: 33272571; PMCID: PMC7699159.
- Markus SM, Marzo MG, McKenney RJ. New insights into the mechanism of dynein motor regulation by lissencephaly-1. Elife. 2020 Jul 21;9:e59737. doi: 10.7554/eLife.59737. PMID: 32692650; PMCID: PMC7373426.
- Wormser O, Levy Y, Bakhrat A, Bonaccorsi S, Graziadio L, Gatti M, AbuMadighem A, McKenney RJ, Okada K, El Riati S, Har-Vardi I, Huleihel M, Levitas E, Birk OS, Abdu U. Absence of SCAPER causes male infertility in humans and Drosophila by modulating microtubule dynamics during meiosis. J Med Genet. 2021 Apr;58(4):254-263. doi: 10.1136/jmedgenet-2020-1069
- Doval F, Chiba K, McKenney RJ, Ori-McKenney KM, Vershinin MD. Temperature-dependent activity of kinesins is regulable. Biochem Biophys Res Commun. 2020 Jul 30;528(3):528-530. doi: 10.1016/j.bbrc.2020.05.157. Epub 2020 Jun 4. PMID: 32507595; PMCID: PMC7366363.