Dr. Ashwani Sharma

Ashwani-pic-1

Scientist

Paul Scherrer Institute
Forschungsstrasse 111
5232 Villigen PSI
Switzerland
Telefon
+41 56 310 40 47

Ashwani completed his doctoral studies at ICGEB (New Delhi India), on a project that aimed at the structural and functional characterization of malaria parasite proteins involved in crosstalk with the human cell components. He performed his postdoctoral research at PSI and then at EPFL where he successfully applied a combination of structural and biophysical techniques to study mammalian tubulin-protein and tubulin-drug complexes. Subsequently, with the support from a Novartis FreeNovation grant and a SNF Spark grant, he initiated a project together with Dr. Natacha Gaillard on the Apicomplexan microtubule cytoskeleton at PSI. Additionally, Ashwani is leading and managing Biophysics Resources at PSI (https://www.psi.ch/en/lbr/facilities).   

Eukaryotic parasites belonging to the phylum Apicomplexa invade host cells via a complex and active process which involves the coordinated action of multiple organelles located at the apical end of the parasites (apical complex, APC). The APC comprises of a tubulin based conoid, multiple secretory organelles (rhoptries and micronemes) and inter-conoidal microtubules (MTs). Although, the APC is implicated in parasite invasion by secreting parasite proteins into the host cells, to date, molecular details of the role of the MTs in APC secretion and host cell invasion remains largely unknown. Towards this end, we are using recombinant protein technologies in combination with biochemical and structural methods to discover the interactions of host and parasite MTs with the parasite proteins involved in host cell invasion.

Inhibition of cell division by using tubulin targeting, antimitotic compounds has been the most successful strategy for cancer treatment up to now. Implementing a similar strategy to arrest parasite replication using apicomplexan tubulin specific inhibitors offers a completely new and attractive avenue towards anti-apicomplexan drug discovery. Our research interest is to exploit the structural peculiarities of apicomplexan tubulin drug-binding sites in comparison to their mammalian counterparts to develop novel anti-tubulin drugs specific for protozoan parasites.

2019

AIMS Award, Principal Investigator

Award from Atomwise Inc. for AI based anti-parasite drug discovery

2019

Spark, SNF, Principal Investigator 

Host cytoskeleton manipulation by Apicomplexan parasites: structural and functional investigation of the RON complex

2017

Novartis Freenovation Grant, Co-Principal Investigator

Towards the Structure Based Design of Broad Spectrum Anti-Apicomplexan Drugs

2012

EMBO Long Term Fellowship

(2012)
  • Mühlethaler T, Olieric N, Ehrhard VA, Wranik M, Standfuss J, Sharma A, et al.
    Crystallization systems for the high-resolution structural analysis of tubulin-ligand complexes
    In: Inaba H, ed. Microtubules. Methods and protocols. Methods in molecular biology. New York: Humana Press; 2022:349-374. https://doi.org/10.1007/978-1-0716-1983-4_23
    DORA PSI
  • Gaillard N, Sharma A, Abbaali I, Liu T, Shilliday F, Cook AD, et al.
    Inhibiting parasite proliferation using a rationally designed anti-tubulin agent
    EMBO Molecular Medicine. 2021; 13(11): e13818 (12 pp.). https://doi.org/10.15252/emmm.202013818
    DORA PSI
  • Sharma A, Olieric N, Steinmetz MO
    Centriole length control
    Current Opinion in Structural Biology. 2021; 66: 89-95. https://doi.org/10.1016/j.sbi.2020.10.011
    DORA PSI
  • Kashyap AS, Fernandez-Rodriguez L, Zhao Y, Monaco G, Trefny MP, Yoshida N, et al.
    GEF-H1 signaling upon microtubule destabilization is required for dendritic cell activation and specific anti-tumor responses
    Cell Reports. 2019; 28(13): 3367-3380.e1. https://doi.org/10.1016/j.celrep.2019.08.057
    DORA PSI
  • La Sala G, Olieric N, Sharma A, Viti F, de Asis Balaguer Perez F, Huang L, et al.
    Structure, thermodynamics, and kinetics of plinabulin binding to two tubulin isotypes
    Chem. 2019; 5(11): 2969-2986. https://doi.org/10.1016/j.chempr.2019.08.022
    DORA PSI
  • Aher A, Kok M, Sharma A, Rai A, Olieric N, Rodriguez-Garcia R, et al.
    CLASP suppresses microtubule catastrophes through a single TOG domain
    Developmental Cell. 2018; 46(1): 40-58.e8. https://doi.org/10.1016/j.devcel.2018.05.032
    DORA PSI
  • Sharma A, Gerard SF, Olieric N, Steinmetz MO
    Cep120 promotes microtubule formation through a unique tubulin binding C2 domain
    Journal of Structural Biology. 2018; 203(1): 62-70. https://doi.org/10.1016/j.jsb.2018.01.009
    DORA PSI
  • Sharma A, Sáez-Calvo G, Olieric N, de Asís Balaguer F, Barasoain I, Lamberth C, et al.
    Quinolin-6-yloxyacetamides are microtubule destabilizing agents that bind to the colchicine site of tubulin
    International Journal of Molecular Sciences. 2017; 18(7): 1336 (11 pp.). https://doi.org/10.3390/ijms18071336
    DORA PSI
  • Sáez-Calvo G, Sharma A, de Asís Balaguer F, Barasoain I, Rodríguez-Salarichs J, Olieric N, et al.
    Triazolopyrimidines are microtubule-stabilizing agents that bind the vinca inhibitor site of tubulin
    Cell Chemical Biology. 2017; 24(6): 737-750. https://doi.org/10.1016/j.chembiol.2017.05.016
    DORA PSI
  • Burger D, Stihle M, Sharma A, Di Lello P, Benz J, D'Arcy B, et al.
    Crystal structures of the human doublecortin C- and N-terminal domains in complex with specific antibodies
    Journal of Biological Chemistry. 2016; 291(31): 16292-16306. https://doi.org/10.1074/jbc.M116.726547
    DORA PSI
  • Sharma A, Aher A, Dynes NJ, Frey D, Katrukha EA, Jaussi R, et al.
    Centriolar CPAP/SAS-4 imparts slow processive microtubule growth
    Developmental Cell. 2016; 37(4): 362-376. https://doi.org/10.1016/j.devcel.2016.04.024
    DORA PSI
  • Purification, crystallization and preliminary crystallographic studies of C-terminal RNA recognition motif (RRM-3) of human ELAV-type RNA-binding protein 3 (ETR-3).
    Kashyap M, Sharma A, Bhavesh NS.
    Acta Crystallogr Sect F Struct Biol Cryst Commun. 69(Pt 10), 1107-09 (2013).
    DOI: http://dx.doi.org/10.1107/S1744309113023439.
  • Structural insights into thioredoxin-2:a component of malaria parasite protein secretion machinery.
    Sharma A, Sharma A, Dixit S, Sharma A.
    Scientific Reports 1:179, (2011).
    DOI: http://dx.doi.org/10.1038/srep00179.
  • Crystal structure of soluble domain of malaria sporozoite protein UIS3 in complex with lipid.
    Sharma A, Yogavel M, Akhouri RR, Gill J, Sharma A.
    J Biol Chem. 283(35), 24077-88 (2008).
    DOI: http://dx.doi.org/10.1074/jbc.M801946200.
  • Role of Plasmodium falciparum thrombospondin-related anonymous protein in host-cell interactions.
    Akhouri RR, Sharma A, Malhotra P, Sharma A.
    Malar J. 7:63, (2008).
    DOI: http://dx.doi.org/10.1186/1475-2875-7-63.