Publications by authors named "Richard Kumaran Kandasamy"

4 Publications

  • Page 1 of 1

A widespread role for SLC transmembrane transporters in resistance to cytotoxic drugs.

Nat Chem Biol 2020 04 9;16(4):469-478. Epub 2020 Mar 9.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

Solute carriers (SLCs) are the largest family of transmembrane transporters in humans and are major determinants of cellular metabolism. Several SLCs have been shown to be required for the uptake of chemical compounds into cellular systems, but systematic surveys of transporter-drug relationships in human cells are currently lacking. We performed a series of genetic screens in a haploid human cell line against 60 cytotoxic compounds representative of the chemical space populated by approved drugs. By using an SLC-focused CRISPR-Cas9 library, we identified transporters whose absence induced resistance to the drugs tested. This included dependencies involving the transporters SLC11A2/SLC16A1 for artemisinin derivatives and SLC35A2/SLC38A5 for cisplatin. The functional dependence on SLCs observed for a significant proportion of the screened compounds suggests a widespread role for SLCs in the uptake and cellular activity of cytotoxic drugs and provides an experimentally validated set of SLC-drug associations for a number of clinically relevant compounds.
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http://dx.doi.org/10.1038/s41589-020-0483-3DOI Listing
April 2020

SLAMF1 is required for TLR4-mediated TRAM-TRIF-dependent signaling in human macrophages.

J Cell Biol 2018 04 12;217(4):1411-1429. Epub 2018 Feb 12.

Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.

Signaling lymphocytic activation molecule family 1 (SLAMF1) is an Ig-like receptor and a costimulatory molecule that initiates signal transduction networks in a variety of immune cells. In this study, we report that SLAMF1 is required for Toll-like receptor 4 (TLR4)-mediated induction of interferon β (IFNβ) and for killing of Gram-negative bacteria by human macrophages. We found that SLAMF1 controls trafficking of the Toll receptor-associated molecule (TRAM) from the endocytic recycling compartment (ERC) to phagosomes. In resting macrophages, SLAMF1 is localized to ERC, but upon addition of , it is trafficked together with TRAM from ERC to phagosomes in a Rab11-dependent manner. We found that endogenous SLAMF1 protein interacted with TRAM and defined key interaction domains as amino acids 68 to 95 of TRAM as well as 15 C-terminal amino acids of SLAMF1. Interestingly, the SLAMF1-TRAM interaction was observed for human but not mouse proteins. Overall, our observations suggest that SLAMF1 is a new target for modulation of TLR4-TRAM-TRIF inflammatory signaling in human cells.
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http://dx.doi.org/10.1083/jcb.201707027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881497PMC
April 2018

Toward effective sharing of high-dimensional immunology data.

Nat Biotechnol 2014 Aug;32(8):755-9

The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

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http://dx.doi.org/10.1038/nbt.2974DOI Listing
August 2014

Protein interaction networks in innate immunity.

Trends Immunol 2013 Dec 2;34(12):610-9. Epub 2013 Jul 2.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

The immune response to pathogens is controlled by complex and tightly regulated molecular networks. Recent technological advances have empowered approaches to investigate innate immune signaling and monitor host-pathogen interactions at a systems level. Protein complexes are key players in pathogen recognition and integrate much of the host molecular responses that occur at the transcriptional and translational level. The ability to monitor protein complex abundance, dynamics, and composition is therefore important to understand the ability of cells to mount the appropriate immune response. Here, we focus on current proteomics technologies applied to identify the protein complexes involved, and highlight recent studies illustrating the power of these approaches to unravel how the dedicated molecular machinery is integrated with other cellular processes to safeguard homeostasis.
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http://dx.doi.org/10.1016/j.it.2013.05.002DOI Listing
December 2013