Victor SHAHIN
Institute of Physiology II, University of Muenster Medical Faculty,
Germany

Facilitating nuclear delivery of pharmacological
nanoparticles by interfering with the selectivenuclear pore barrier

Contact : shahin [at sign] uni-muenster.dePlease replace [at sign] with @.

Victor SHAHIN
Institute of Physiology II, Medical Faculty of Münster University, Germany

Research Interests
Atomic Force Microscopy, Nanomedicine, Nanotechnology, Physiology, Cancer Physiology

Nuclear pore complexes (NPCs) are elaborate nano-transporters built from diverse proteins termed nucleoporins(Nups). They control all nucleocytoplasmic transport and form a stringent barrier between the cytosol and thenucleus. While selective nucleocytoplasmic transport enables translocation of macromolecules up to striking sizes
approaching megadalton-scale, the upper cutoff for unselective diffusion is at 40 kDa. Elevating the cutoff is ofEducation
2002

particular importance for nuclear delivery of therapeutic nanoparticles that are destined to act inside the nucleus.
We study compounds that interfere with the biophysical and functional properties of NPC. The ultimate goal is toDoctor of Pharmacy and Physiology, Pharmacy and Medical Faculties ofraise the upper NPC cutoff for passive nuclear delivery to a substantial degree, relevant for therapeutic

Münster University, Germany

nanoparticles. We present two different classes of compounds that significantly lower the stringency of the NPC
barrier, by two distinct modes of action, interfering with either the NPC channel barrier or the NPC scaffold. Our
ongoing research reveals that former class facilitates nuclear delivery of 5kbp pDNA in up to 10-20% of the tested

Professional Career

cells, compared to no delivery at all in control conditions. We envisage that the various tested compounds of this2002 - 2006

Postdoc, Medical Faculty of Münster/Germany, and University of Cambridge UK

therapeutic nanoparticles.

2006 - 2015

Associate Prof. and group leader, Inst. of Physiology II, Medical Faculty of Münster Univ.

2015 - present

Prof. for Physiology, Inst. of Physiology II, Medical Faculty of Münster Univ.

class may serve as lead substances and usher in the design of potent new strategies to increase nuclear delivery ofHonors
2011

Rolf-Dierichs-Stiftung, ‘Innovative Medical Research’ award at the Medical Faculty, Münster

2018

Distinguished lecturer of the year award’ Medical Faculty, Münster

Publications
Liashkovich, I., Rosso, G., Shahin, V., (2019). Nuclear envelope permeability barrier as a fast-response intracellular mechanostat. Advanced Science,

1. 2019 Aug 29;6(21):1900709. doi: 10.1002/advs.201900709.

Azzam, I., Liashkovich, I., Luchtefeld, I., Kouzel IU, Shahin, V., (2019). Facilitating plasmid nuclear delivery be interfering with the selective nuclear

2. pore barrier. Bioeng Transl Med. 2019 Jun 22;4(3):e10136. doi: 10.1002/btm2.10136.

Kramer, A., Liashkovich, I., Oberleithner, H., Ludwig, S., Mazur, I., Shahin, V. 2008. Apoptosis leads to a degradation of vital components of active

3. nuclear transport and a dissociation of the nuclear lamina. PNAS. 105:11236-41.

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Fig. 1. A: Scheme of the cell nucleus. B: AFM images of the cytoplasmic face of the nuclear
envelope (large image, 4 x 4 μm) and selected NPCs (magnification, bottom right, 280 x 280 nm)
of Xenopus laevis oocytes.From: Shahin,V. (2006). The nuclear barrier is structurally andfunctionally highly responsive to glucocorticoids. BioEssays 28, 935-942.

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