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  • Malka B. Finkelstein, M.D.

Malka B. Finkelstein, M.D.

Malka B. Finkelstein

Research Assistant Professor, Department of Biochemistry

Contact Information

718.430.3451matthieu.benoit@einsteinmed.edu

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus

1300 Morris Park Avenue
Ullmann Building, Room 217
Bronx, NY 10461

Research Profiles

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Professional Interests

Biological molecular motors use chemical energy to generate mechanical work. They are at the center of many cell processes like cell division, DNA replication, cellular homeostasis, organelle movement, axonal transport, cilia motility, establishment of the main axes during development, etc. As a consequence anomalies at the level of these motor or their abnormal expressions are associated to severe diseases (neurological and development disorders, cancers, etc.).

I'm interested in the understanding of biological molecular motors at the atomic level. I'm also interested in two translational research topics that benefit from this understanding. First the design of drugs to modulate the activity of these motors in a pathological context. Second, the design of biologically-derived synthetic motors that can have applications in biotechnology and medicine.

I'm currently focusing on kinesins, a superfamily of motor proteins that couples ATP hydrolysis to a wide range of activities in the cell. Some kinesins transport cellular cargos (organelles, messenger RNA, etc) along microtubules. Many others are key players during cell division where they support activities like microtubule depolymerization or polymerization, sliding of antiparallel microtubules, chromosome movement, etc.  It is however not well understood how members of the kinesin superfamily can have such a wide range of activities. Obtaining high resolution information of these motors during the ATP hydrolysis cycle enable to identify the chemo-mechanical couplings that underpin their activity. Kinesins appear increasingly attractive as target for anticancer therapies and I'm also interested in the modulation of kinesin motors using drugs. The design of these drugs strongly benefits from the understanding of the mechanism of these kinesins at high spatial and temporal resolutions.

Methodology wise, I use primarily cryo-electron microscopy which depending of the question is combined with other molecular biophysical methods including single molecules fluorescence techniques, multidimensional liquid state Nuclear Magnetic Resonance, Electron paramagnetic resonance, Analytical Ultracentrifugation, Isothermal Calorimetry and Multiple-angle Laser Light Scattering. I'm also working on methodological development in cryo-EM image processing and single molecules methods to tackle challenging questions regarding molecular motors.


Selected Publications

Benoit MPMH, Asenjo AB, Paydar M, Dhakal S, Kwok BH, Sosa H. Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14. Nature Communications. 2021 Jun 15;12(1):3637. doi: 10.1038/s41467-021-23581-3. PMID: 34131133
BioRxiv, https://doi.org/10.1101/2020.06.01.128371

Benoit MPMH, Asenjo AB, Sosa H. Cryo-EM Reveals the Structural Basis of Microtubule Depolymerization by Kinesin-13s. Nature Communications. 2018; 9: 1662. doi: 10.1038/s41467-018-04044-8. PMID: 29695795.
- Recommanded in F1000Prime, 10.3410/f.733100735.793547057.
- BioRxiv, https://doi.org/10.1101/206268

Benoit MPMH, Sosa H. Use of Single Molecule Fluorescence Polarization Microscopy to Study Protein Conformation and Dynamics of Kinesin-Microtubule Complexes. Methods Mol Biol. 2018;1665:199-216. doi: 10.1007/978-1-4939-7271-5_11. PMID: 28940071.

Chatterjee C*, Benoit MPMH*, DePaoli V, Diaz-Valencia JD, Asenjo AB, Gerfen GJ, Sharp DJ, Sosa H. Distinct Interaction Modes of the Kinesin-13 Motor Domain with the Microtubule. Biophys J. 2016 Apr 12;110(7):1593-604. doi: 10.1016/j.bpj.2016.02.029. PMID: 27074684. (* equal contribution).

Suarez IP, Burdisso P, Benoit MPMH, Boisbouvier J, Rasia RM. Induced folding in RNA recognition by Arabidopsis thaliana DCL1. Nucleic Acids Res. 2015 Jul 27;43(13):6607-19. doi: 10.1093/nar/gkv627. PMID: 26101256.

Benoit MPMH, Imbert L, Palencia A, Pérard J, Ebel C, Boisbouvier J, Plevin MJ. The RNA-binding region of human TRBP interacts with microRNA precursors through two independent domains. Nucleic Acids Res. 2013 Apr;41(7):4241-52. doi: 10.1093/nar/gkt086. PMID: 23435228.

Benoit MPMH, Plevin MJ. Backbone resonance assignments of the micro-RNA precursor binding region of human TRBP. Biomol NMR Assign. 2013 Oct;7(2):229-33. doi: 10.1007/s12104-012-9416-8. PMID: 22875687.

Related News

  • Snapshots of a Molecular Motor
    Research Brief
    Snapshots of a Molecular Motor

    Jul 12, 2021

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