satinder samra | University College London (original) (raw)

Papers by satinder samra

Research paper thumbnail of Microglial Expression of the Wnt Signaling ModulatorDKK2Differs between Human Alzheimer’s Disease Brains and Mouse Neurodegeneration Models

eneuro

Wnt signaling is crucial for synapse and cognitive function. Indeed, deficient Wnt signaling is c... more Wnt signaling is crucial for synapse and cognitive function. Indeed, deficient Wnt signaling is causally related to increased expression ofDKK1,an endogenous negative Wnt regulator, and synapse loss, both of which likely contribute to cognitive decline in Alzheimer’s disease (AD). Increasingly, AD research efforts have probed the neuroinflammatory role of microglia, the resident immune cells of the CNS, which have furthermore been shown to be modulated by Wnt signaling. TheDKK1homologDKK2has been previously identified as an activated response and/or disease-associated microglia (DAM/ARM) gene in a mouse model of AD. Here, we performed a detailed analysis ofDKK2in mouse models of neurodegeneration, and in human AD brain. InAPP/PS1andAPPNL-G-FAD mouse model brains as well as inSOD1G93AALS mouse model spinal cords, but not in control littermates, we demonstrated significant microgliosis and microglialDkk2mRNA upregulation in a disease-stage-dependent manner. In the AD models, these DAM...

Research paper thumbnail of Microglial expression of the Wnt signalling modulator DKK2 differs between human Alzheimer’s disease brains and mouse neurodegeneration models

Wnt signalling is crucial for synapse and cognitive function. Indeed, deficient Wnt signalling is... more Wnt signalling is crucial for synapse and cognitive function. Indeed, deficient Wnt signalling is causally related to increased expression of DKK1, an endogenous negative Wnt regulator, and synapse loss, both of which likely contribute to cognitive decline in Alzheimer’s disease (AD). Increasingly, AD research efforts have probed the neuroinflammatory role of microglia, the resident immune cells of the central nervous system (CNS), which have furthermore been shown to be modulated by Wnt signalling.The DKK1 homologue DKK2 has been previously identified as an activated response and/or disease-associated microglia (DAM/ARM) gene in a mouse model of AD. Here we performed a detailed analysis of DKK2 in mouse models of neurodegeneration, and in human AD brain. In APP/PS1 and APPNL-G-F AD mouse model brains as well as in SOD1G93A ALS mouse model spinal cords, but not in control littermates, we demonstrated significant microgliosis and microglial Dkk2 mRNA upregulation in a disease-stage d...

Research paper thumbnail of PGN 1091, a novel 5-HT2B receptor antagnist for the treatment of irritable bowel syndrome

Gastroenterology, 2003

volume. Neostigmine increased colonic tone by ~ 35% in all patients, I compliance, i.e. Prl/2 inc... more volume. Neostigmine increased colonic tone by ~ 35% in all patients, I compliance, i.e. Prl/2 increased from [14.6(1.5) before vs 22.0(2.0) after neostigmine; p<0.001l and induced HAPCs (mean: 11, range: 0-43) in 8/9 patients. Conclusions: Pressure-volume curves reveal increased or reduced colonic compliance after SCL Though gastrocolonic response is reduced, response to neostigmine was preserved, arguing against colonic inertia

Research paper thumbnail of Upstream Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Element-1, a Novel and Essential Regulatory DNA Motif in the Human TIMP-1 Gene Promoter, Directly Interacts with a 30-kDa Nuclear Protein

Journal of Biological Chemistry, 2000

Elevated expression of the tissue inhibitor of metalloproteinases-1 (TIMP-1) protein and mRNA has... more Elevated expression of the tissue inhibitor of metalloproteinases-1 (TIMP-1) protein and mRNA has been reported in human diseases including cancers and tissue fibrosis. Regulation of TIMP-1 gene expression is mainly mediated at the level of gene transcription and involves the activation of several well known transcription factors including those belonging to the AP-1, STAT, and Pea3/Ets families. In the current study, we have used DNase-1 footprinting to identify a new regulatory element (5-TGTGGTTTCCG-3) present in the human * This work was carried out in collaboration with Zeneca Pharmaceuticals UK and was supported in part by Wellcome Trust Grant 050443/Z (to M. J. P. A. and D. A. M.) and a grant from the Sir James Knott Trust (to M. J. P. A.

Research paper thumbnail of Abstract B30: Development of robust in vitro 3D models of human tumors for the identification and evaluation of anti-cancer drugs

Cancer Research, 2017

Currently in vivo testing of animals is still the gold standard for drug development and testing ... more Currently in vivo testing of animals is still the gold standard for drug development and testing of cytotoxic compounds. With the demand for non-animal alternatives raising here we compared the development and functionality of two 3D culture models for tumor spheroids. Firstly 3D tumor spheroids were generated from lung cancer cell lines (NCI-H1650, NCI-H2170, NCI-H1975 and HCC-827) with known EGFR pathway mutations, and also primary isolated lung cancer epithelial cells, by encapsulation within an Alginate matrix to produced isogenic cell populations. Additionally, spheroids were co-cultured alongside primary Cancer-Associated Fibroblasts (CAFs). Following generation (7 days), spheroids (up to 500µm diameter) were treated with cytotoxic agents. The presence of CAFs attenuated the growth of smaller tumor spheroids (<100μm) although drug responses were not markedly changed in larger spheroids. Secondly, 3D tumor spheroids were generated using the OrganDot system (Asterand Bioscien...

Research paper thumbnail of Microglial Expression of the Wnt Signaling ModulatorDKK2Differs between Human Alzheimer’s Disease Brains and Mouse Neurodegeneration Models

eneuro

Wnt signaling is crucial for synapse and cognitive function. Indeed, deficient Wnt signaling is c... more Wnt signaling is crucial for synapse and cognitive function. Indeed, deficient Wnt signaling is causally related to increased expression ofDKK1,an endogenous negative Wnt regulator, and synapse loss, both of which likely contribute to cognitive decline in Alzheimer’s disease (AD). Increasingly, AD research efforts have probed the neuroinflammatory role of microglia, the resident immune cells of the CNS, which have furthermore been shown to be modulated by Wnt signaling. TheDKK1homologDKK2has been previously identified as an activated response and/or disease-associated microglia (DAM/ARM) gene in a mouse model of AD. Here, we performed a detailed analysis ofDKK2in mouse models of neurodegeneration, and in human AD brain. InAPP/PS1andAPPNL-G-FAD mouse model brains as well as inSOD1G93AALS mouse model spinal cords, but not in control littermates, we demonstrated significant microgliosis and microglialDkk2mRNA upregulation in a disease-stage-dependent manner. In the AD models, these DAM...

Research paper thumbnail of Microglial expression of the Wnt signalling modulator DKK2 differs between human Alzheimer’s disease brains and mouse neurodegeneration models

Wnt signalling is crucial for synapse and cognitive function. Indeed, deficient Wnt signalling is... more Wnt signalling is crucial for synapse and cognitive function. Indeed, deficient Wnt signalling is causally related to increased expression of DKK1, an endogenous negative Wnt regulator, and synapse loss, both of which likely contribute to cognitive decline in Alzheimer’s disease (AD). Increasingly, AD research efforts have probed the neuroinflammatory role of microglia, the resident immune cells of the central nervous system (CNS), which have furthermore been shown to be modulated by Wnt signalling.The DKK1 homologue DKK2 has been previously identified as an activated response and/or disease-associated microglia (DAM/ARM) gene in a mouse model of AD. Here we performed a detailed analysis of DKK2 in mouse models of neurodegeneration, and in human AD brain. In APP/PS1 and APPNL-G-F AD mouse model brains as well as in SOD1G93A ALS mouse model spinal cords, but not in control littermates, we demonstrated significant microgliosis and microglial Dkk2 mRNA upregulation in a disease-stage d...

Research paper thumbnail of PGN 1091, a novel 5-HT2B receptor antagnist for the treatment of irritable bowel syndrome

Gastroenterology, 2003

volume. Neostigmine increased colonic tone by ~ 35% in all patients, I compliance, i.e. Prl/2 inc... more volume. Neostigmine increased colonic tone by ~ 35% in all patients, I compliance, i.e. Prl/2 increased from [14.6(1.5) before vs 22.0(2.0) after neostigmine; p<0.001l and induced HAPCs (mean: 11, range: 0-43) in 8/9 patients. Conclusions: Pressure-volume curves reveal increased or reduced colonic compliance after SCL Though gastrocolonic response is reduced, response to neostigmine was preserved, arguing against colonic inertia

Research paper thumbnail of Upstream Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Element-1, a Novel and Essential Regulatory DNA Motif in the Human TIMP-1 Gene Promoter, Directly Interacts with a 30-kDa Nuclear Protein

Journal of Biological Chemistry, 2000

Elevated expression of the tissue inhibitor of metalloproteinases-1 (TIMP-1) protein and mRNA has... more Elevated expression of the tissue inhibitor of metalloproteinases-1 (TIMP-1) protein and mRNA has been reported in human diseases including cancers and tissue fibrosis. Regulation of TIMP-1 gene expression is mainly mediated at the level of gene transcription and involves the activation of several well known transcription factors including those belonging to the AP-1, STAT, and Pea3/Ets families. In the current study, we have used DNase-1 footprinting to identify a new regulatory element (5-TGTGGTTTCCG-3) present in the human * This work was carried out in collaboration with Zeneca Pharmaceuticals UK and was supported in part by Wellcome Trust Grant 050443/Z (to M. J. P. A. and D. A. M.) and a grant from the Sir James Knott Trust (to M. J. P. A.

Research paper thumbnail of Abstract B30: Development of robust in vitro 3D models of human tumors for the identification and evaluation of anti-cancer drugs

Cancer Research, 2017

Currently in vivo testing of animals is still the gold standard for drug development and testing ... more Currently in vivo testing of animals is still the gold standard for drug development and testing of cytotoxic compounds. With the demand for non-animal alternatives raising here we compared the development and functionality of two 3D culture models for tumor spheroids. Firstly 3D tumor spheroids were generated from lung cancer cell lines (NCI-H1650, NCI-H2170, NCI-H1975 and HCC-827) with known EGFR pathway mutations, and also primary isolated lung cancer epithelial cells, by encapsulation within an Alginate matrix to produced isogenic cell populations. Additionally, spheroids were co-cultured alongside primary Cancer-Associated Fibroblasts (CAFs). Following generation (7 days), spheroids (up to 500µm diameter) were treated with cytotoxic agents. The presence of CAFs attenuated the growth of smaller tumor spheroids (<100μm) although drug responses were not markedly changed in larger spheroids. Secondly, 3D tumor spheroids were generated using the OrganDot system (Asterand Bioscien...