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Nachiket Vartak

About Nachiket Vartak:
No description specified

SEEK ID: https://seek.lisym.org/people/34

Location: Germany

Expertise: Molecular Biology, Systems Biology, Signal transduction, in vivo imaging, Hepatocytes, Spatio-temporal Modelling, functional imaging

Tools: 3D reconstruction, in vivo 2-photon imaging, live cell imaging, confocal microscopy, image analysis

ORCID: Not specified

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LiSyM-Krebs Partnering

This generic project is intended to be a forum for all LiSyM partner and external stakeholders interested in participating in the BMBF initiative LiSyM-Krebs.

Public web page: https://www.ptj.de/projektfoerderung/gesundheitsforschung/lisym-krebs

LiSyM network

This comprises the whole LiSyM network

Public web page: http://www.lisym.org

Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM)

Lipid droplet accumulation is the primary cellular phenotype that is interpreted as fat deposition at organ level in steatosis. The goal of this project is to establish a model that bridges molecular lipogenic stimuli with compromised liver functions.
Approach:
– Functional imaging of hepatic transport mechanisms
– Systems modeling of lipid droplet formation

Public web page: Not specified

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Intravital multi-modal flux analysis reveals the transport mechanism of bile acids through hepatic microconduits
Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM)

Abstract (Expand)

Small-molecule flux in tissue-microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods applicable to live animals. We developed a methodology … based on dynamic and correlative imaging for quantitative intravital flux analysis. Application to the liver, challenged the prevailing ‘mechano-osmotic’ theory of canalicular bile flow. After active transport across hepatocyte membranes bile salts are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts, diffusion is augmented by regulatable advection. We corroborate these observations with in silico simulations and pan-species comparisons of lobule size. This study demonstrates a flux mechanism, where the energy invested in transmembrane transport entropically dissipates in a sub-micron scale vessel network.

Authors: Nachiket Vartak, Georgia Guenther, Florian Joly, Amruta Damle-Vartak, Gudrun Wibbelt, Jörns Fickel, Simone Jörs, Brigitte Begher-Tibbe, Adrian Friebel, Kasimir Wansing, Ahmed Ghallab, Marie Rosselin, Noemie Boissier, Irene Vignon-Clementel, Christian Hedberg, Fabian Geisler, Heribert Hofer, Peter Jansen, Stefan Hoehme, Dirk Drasdo, Jan Hengstler

Date Published: No date defined

Journal: Not specified

The ascending pathophysiology of cholestatic liver disease.
Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM)

Abstract (Expand)

In this review we develop the argument that cholestatic liver diseases, particularly primary biliary cholangitis and primary sclerosing cholangitis (PSC), evolve over time with anatomically an ascending … course of the disease process. The first and early lesions are in "downstream" bile ducts. This eventually leads to cholestasis, and this causes bile salt (BS)-mediated toxic injury of the "upstream" liver parenchyma. BS are toxic in high concentration. These concentrations are present in the canalicular network, bile ducts, and gallbladder. Leakage of bile from this network and ducts could be an important driver of toxicity. The liver has a great capacity to adapt to cholestasis, and this may contribute to a variable symptom-poor interval that is often observed. Current trials with drugs that target BS toxicity are effective in only about 50%-60% of primary biliary cholangitis patients, with no effective therapy in PSC. This motivated us to develop and propose a new view on the pathophysiology of primary biliary cholangitis and PSC in the hope that these new drugs can be used more effectively. These views may lead to better stratification of these diseases and to recommendations on a more "tailored" use of the new therapeutic agents that are currently tested in clinical trials. Apical sodium-dependent BS transporter inhibitors that reduce intestinal BS absorption lower the BS load and are best used in cholestatic patients. The effectiveness of BS synthesis-suppressing drugs, such as farnesoid X receptor agonists, is greatest when optimal adaptation is not yet established. By the time cytochrome P450 7A1 expression is reduced these drugs may be less effective. Anti-inflammatory agents are probably most effective in early disease, while drugs that antagonize BS toxicity, such as ursodeoxycholic acid and nor-ursodeoxycholic acid, may be effective at all disease stages. Endoscopic stenting in PSC should be reserved for situations of intercurrent cholestasis and cholangitis, not for cholestasis in end-stage disease. These are arguments to consider a step-wise pathophysiology for these diseases, with therapy adjusted to disease stage. An obstacle in such an approach is that disease stage-defining biomarkers are still lacking. This review is meant to serve as a call to prioritize the development of biomarkers that help to obtain a better stratification of these diseases. (Hepatology 2017;65:722-738).

Authors: Peter Jansen, Ahmed Ghallab, Nachiket Vartak, R. Reif, Frank Lammert, Jochen Hampe, Jan Hengstler

Date Published: 17th Feb 2017

Journal: Hepatology

Single cell polarity in liquid phase facilitates tumour metastasis.
Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM)

Abstract (Expand)

Dynamic polarisation of tumour cells is essential for metastasis. While the role of polarisation during dedifferentiation and migration is well established, polarisation of metastasising tumour cells … during phases of detachment has not been investigated. Here we identify and characterise a type of polarisation maintained by single cells in liquid phase termed single-cell (sc) polarity and investigate its role during metastasis. We demonstrate that sc polarity is an inherent feature of cells from different tumour entities that is observed in circulating tumour cells in patients. Functionally, we propose that the sc pole is directly involved in early attachment, thereby affecting adhesion, transmigration and metastasis. In vivo, the metastatic capacity of cell lines correlates with the extent of sc polarisation. By manipulating sc polarity regulators and by generic depolarisation, we show that sc polarity prior to migration affects transmigration and metastasis in vitro and in vivo.

Authors: A. Lorentzen, P. F. Becker, J. Kosla, M. Saini, K. Weidele, P. Ronchi, C. Klein, M. J. Wolf, F. Geist, B. Seubert, M. Ringelhan, D. Mihic-Probst, K. Esser, M. Roblek, F. Kuehne, G. Bianco, T. O'Connor, Q. Muller, K. Schuck, S. Lange, D. Hartmann, S. Spaich, O. Gross, J. Utikal, S. Haferkamp, M. R. Sprick, Amruta Damle Vartak, A. Hapfelmeier, N. Huser, U. Protzer, A. Trumpp, D. Saur, Nachiket Vartak, C. A. Klein, B. Polzer, L. Borsig, M. Heikenwalder

Date Published: 2nd Mar 2018

Journal: Nat Commun

3D visualization of the biliary tree by X-ray phase-contrast computed tomography
Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM)

Abstract

Not specified

Author: Amruta Damle Vartak

Date Published: 1st Dec 2018

Journal: Arch Toxicol

Bile micro-infarcts in cholestasis are initiated by rupture of the apical hepatocyte membrane and cause shunting of bile to sinusoidal blood
Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP)

Abstract

Not specified

Authors: Ahmed Ghallab, Ute Hofmann, Selahaddin Sezgin, Nachiket Vartak, Reham Hassan, Ayham Zaza, Patricio Godoy, Kai Markus Schneider, Georgia Guenther, Yasser A Ahmed, Aya A Abbas, Verena Keitel, Lars Kuepfer, Steven Dooley, Frank Lammert, Christian Trautwein, Michael Spiteller, Dirk Drasdo, Alan F Hofmann, Peter Jansen, Jan Hengstler, Raymond Reif

Date Published: 13th Aug 2018

Journal: HEP

Participant Abstracts LiSyM Retreat 2020
LiSyM network
No description specified

Creator: Nachiket Vartak

Contributor: Nachiket Vartak

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LiSyM Ph.D Postdoc Retreat 2020

Venue : Evangelische Tagungsstätte Hofgeismar, Kassel-Wilhelmshöhe

This young scientist retreat is being organized by the Junior Group Leaders, Madlen Matz-Soja, Matthias König, Ahmed Ghallab and Nachiket Vartak.

Start Date: 29th Jan 2020

End Date: 31st Jan 2020

Event Website: http://bit.ly/lisymretreat2020

Country:  DE

City: Hofgeismar

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