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Nachiket Vartak

About Nachiket Vartak:
No description specified

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

Location: Germany

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

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

ORCID: Not specified

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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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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

Cholestasis-induced adaptive remodeling of interlobular bile ducts.
Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM)

Abstract (Expand)

UNLABELLED: Cholestasis is a common complication in liver diseases that triggers a proliferative response of the biliary tree. Bile duct ligation (BDL) is a frequently used model of cholestasis in … rodents. To determine which changes occur in the three-dimensional (3D) architecture of the interlobular bile duct during cholestasis, we used 3D confocal imaging, surface reconstructions, and automated image quantification covering a period up to 28 days after BDL. We show a highly reproducible sequence of interlobular duct remodeling, where cholangiocyte proliferation initially causes corrugation of the luminal duct surface, leading to an approximately five-fold increase in surface area. This is analogous to the function of villi in the intestine or sulci in the brain, where an expansion of area is achieved within a restricted volume. The increase in surface area is further enhanced by duct branching, branch elongation, and loop formation through self-joining, whereby an initially relatively sparse mesh surrounding the portal vein becomes five-fold denser through elongation, corrugation, and ramification. The number of connections between the bile duct and the lobular bile canalicular network by the canals of Hering decreases proportionally to the increase in bile duct length, suggesting that no novel connections are established. The diameter of the interlobular bile duct remains constant after BDL, a response that is qualitatively distinct from that of large bile ducts, which tend to enlarge their diameters. Therefore, volume enhancement is only due to net elongation of the ducts. Because curvature and tortuosity of the bile duct are unaltered, this enlargement of the biliary tree is caused by branching and not by convolution. CONCLUSION: BDL causes adaptive remodeling that aims at optimizing the intraluminal surface area by way of corrugation and branching.

Authors: Nachiket Vartak, Amruta Damle Vartak, B. Richter, O. Dirsch, U. Dahmen, Seddik Hammad, Jan Hengstler

Date Published: 27th Nov 2015

Journal: Hepatology

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