shyam patel - Academia.edu (original) (raw)
Papers by shyam patel
Frontiers in Public Health
Background: Given the worldwide spread of the 2019 Novel Coronavirus (COVID-19), there is an urge... more Background: Given the worldwide spread of the 2019 Novel Coronavirus (COVID-19), there is an urgent need to identify risk and protective factors and expose areas of insufficient understanding. Emerging tools, such as the Rapid Evidence Map (rEM), are being developed to systematically characterize large collections of scientific literature. We sought to generate an rEM of risk and protective factors to comprehensively inform areas that impact COVID-19 outcomes for different sub-populations in order to better protect the public.Methods: We developed a protocol that includes a study goal, study questions, a PECO statement, and a process for screening literature by combining semi-automated machine learning with the expertise of our review team. We applied this protocol to reports within the COVID-19 Open Research Dataset (CORD-19) that were published in early 2020. SWIFT-Active Screener was used to prioritize records according to pre-defined inclusion criteria. Relevant studies were cat...
Scientific reports, Jan 12, 2017
In regenerative medicine applications, the differentiation stage of implanted stem cells must be ... more In regenerative medicine applications, the differentiation stage of implanted stem cells must be optimized to control cell fate and enhance therapeutic efficacy. We investigated the therapeutic potential of human induced pluripotent stem cell (iPSC)-derived cells at two differentiation stages on peripheral nerve regeneration. Neural crest stem cells (NCSCs) and Schwann cells (NCSC-SCs) derived from iPSCs were used to construct a tissue-engineered nerve conduit that was applied to bridge injured nerves in a rat sciatic nerve transection model. Upon nerve conduit implantation, the NCSC group showed significantly higher electrophysiological recovery at 1 month as well as better gastrocnemius muscle recovery at 5 months than the acellular group, but the NCSC-SC group didn't. Both transplanted NCSCs and NCSC-SCs interacted with newly-growing host axons, while NCSCs showed better survival rate and distribution. The transplanted NCSCs mainly differentiated into Schwann cells with no te...
PLoS ONE, 2011
BORIS (CTCFL) is the paralog of CTCF (CCCTC-binding factor; NM_006565), a ubiquitously expressed ... more BORIS (CTCFL) is the paralog of CTCF (CCCTC-binding factor; NM_006565), a ubiquitously expressed DNA-binding protein with diverse roles in gene expression and chromatin organisation. BORIS and CTCF have virtually identical zinc finger domains, yet display major differences in their respective C-and N-terminal regions. Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a ''cancer-testis'' antigen. However, the expression pattern of BORIS is both a significant and unresolved question in the field of DNA binding proteins. Here, we identify BORIS in the cytoplasm and nucleus of a wide range of normal and cancer cells. We compare the localization of CTCF and BORIS in the nucleus and demonstrate enrichment of BORIS within the nucleolus, inside the nucleolin core structure and adjacent to fibrillarin in the dense fibrillar component. In contrast, CTCF is not enriched in the nucleolus. Live imaging of cells transiently transfected with GFP tagged BORIS confirmed the nucleolar accumulation of BORIS. While BORIS transcript levels are low compared to CTCF, its protein levels are readily detectable. These findings show that BORIS expression is more widespread than previously believed, and suggest a role for BORIS in nucleolar function.
Current Stem Cell Research & Therapy, 2009
Stem cell therapy has a place for future application in the treatment of degenerative diseases. R... more Stem cell therapy has a place for future application in the treatment of degenerative diseases. Regardless of the origin of the stem cell, when placed within a milieu of inflammatory mediator, they will show varied functions. This review focuses on human mesenchymal stem cells (MSCs) and discusses neuronal replacement using multi-and interdisciplinary approaches. We caution the enthusiasm of scientists since there is always the potential for tumor formation, even for adult stem cells. The review places RE-1 silencing transcription factor (REST) gene as central to the understanding of stem cell behavior in the microenvironment of tissue injury. REST is relevant in the development of dopaminergic and peptidergic neurons from MSCs. Premature downregulation of REST by the pro-inflammatory mediator, IL-1 , can prematurely lead to the expression of neurotransmitters, which in turn, could develop rapid crosstalk with immune cells. In-depth inter-and multidisciplinary research will lead to rapid and safe translation of MSCs to patients. An understanding of the changes induced in MSCs by cytokines and other mediators will establish future application of MSCs and other stem cells for safe and effective treatments. This study also alludes to the potential of personalized medicine through engineering and mathematics.
Current Pharmacogenomics and Personalized Medicine, 2011
Bone marrow transplantation is a form of cell therapy that has been in practice for decades for t... more Bone marrow transplantation is a form of cell therapy that has been in practice for decades for the treatment of hematological disorders and solid tumors. Immunosuppressive therapy has been a mainstay for treatment, but the severity of the adverse effects has made it an undesirable choice. Mesenchymal stem cells (MSCs), which reside in the vascular regions of the bone marrow, have been shown to serve as cellular support for the hematopoietic stem cell (HSC) niche. Furthermore, the immune suppressive properties of MSCs have been explored in the treatment of inflammatory and autoimmune disorders. Thus, co-therapy with MSCs has been shown to facilitate engraftment of hematopoietic cells by suppressive graft versus host disease (GvHD). Although the mechanism by which MSCs suppress GvHD is unclear, the experimental evidence suggests that this partly occurs by modulation of immune response such as the induction of regulatory T cells. This paper discusses the role of MSCs as co-therapy for the future of stem cell transplantation, with the overarching theme of personalized medicine for cell-based health interventions.
Genes & …, 2007
Autophagy is a catabolic process involving self-digestion of cellular organelles during starvatio... more Autophagy is a catabolic process involving self-digestion of cellular organelles during starvation as a means of cell survival; however, if it proceeds to completion, autophagy can lead to cell death. Autophagy is also a haploinsufficient tumor suppressor mechanism for mammary tumorigenesis, as the essential autophagy regulator beclin1 is monoallelically deleted in breast carcinomas. However, the mechanism by which autophagy suppresses breast cancer remains elusive. Here we show that allelic loss of beclin1 and defective autophagy sensitized mammary epithelial cells to metabolic stress and accelerated lumen formation in mammary acini. Autophagy defects also activated the DNA damage response in vitro and in mammary tumors in vivo, promoted gene amplification, and synergized with defective apoptosis to promote mammary tumorigenesis. Therefore, we propose that autophagy limits metabolic stress to protect the genome, and that defective autophagy increases DNA damage and genomic instability that ultimately facilitate breast cancer progression.
Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engin... more Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering.
Alzheimer's & Dementia, 2006
Recently, a single nucleotide polymorphism (rs699947) within the promoter of the Vascular Endothe... more Recently, a single nucleotide polymorphism (rs699947) within the promoter of the Vascular Endothelial Growth Factor (VEGF) gene has been reported to be associated with the risk of developing AD in an Italian population (Del bo et al., Ann Neurol. 2005;57:373-80). To validate this observation, we assessed the impact of this SNP on the risk of developing AD in a large French case-control population (respectively nϭ630 and nϭ664). We also evaluated its association with the severity of vascular lesions (arteriosclerosis, white matter loss and cerebral amyloid angiopathy) in AD brains (nϭ76). No association of this SNP with the risk of developing AD was observed (ORϭ1.1, 95% CI [0.9-1.4], pϽ0.39 adjusted on age and gender). No relationship between this SNP and vascular lesions in AD was detected. We next focused on the MEOX2 gene coding for a transcriptional factor involved in vascular differentiation and strongly under-expressed in AD brain endothelial cells (Wu et al., Nat Med. 2005;11:959-65). We analyzed the association of 4 SNPs with the risk of developing AD in a sub-population obtained by drawing lots from our large French case-control population (respectively, nϭ223 and nϭ265). No association was found whatever the studied SNPs. Furthermore, the haplotype distribution did not differ between the AD cases and control sub-populations.
Frontiers in Public Health
Background: Given the worldwide spread of the 2019 Novel Coronavirus (COVID-19), there is an urge... more Background: Given the worldwide spread of the 2019 Novel Coronavirus (COVID-19), there is an urgent need to identify risk and protective factors and expose areas of insufficient understanding. Emerging tools, such as the Rapid Evidence Map (rEM), are being developed to systematically characterize large collections of scientific literature. We sought to generate an rEM of risk and protective factors to comprehensively inform areas that impact COVID-19 outcomes for different sub-populations in order to better protect the public.Methods: We developed a protocol that includes a study goal, study questions, a PECO statement, and a process for screening literature by combining semi-automated machine learning with the expertise of our review team. We applied this protocol to reports within the COVID-19 Open Research Dataset (CORD-19) that were published in early 2020. SWIFT-Active Screener was used to prioritize records according to pre-defined inclusion criteria. Relevant studies were cat...
Scientific reports, Jan 12, 2017
In regenerative medicine applications, the differentiation stage of implanted stem cells must be ... more In regenerative medicine applications, the differentiation stage of implanted stem cells must be optimized to control cell fate and enhance therapeutic efficacy. We investigated the therapeutic potential of human induced pluripotent stem cell (iPSC)-derived cells at two differentiation stages on peripheral nerve regeneration. Neural crest stem cells (NCSCs) and Schwann cells (NCSC-SCs) derived from iPSCs were used to construct a tissue-engineered nerve conduit that was applied to bridge injured nerves in a rat sciatic nerve transection model. Upon nerve conduit implantation, the NCSC group showed significantly higher electrophysiological recovery at 1 month as well as better gastrocnemius muscle recovery at 5 months than the acellular group, but the NCSC-SC group didn't. Both transplanted NCSCs and NCSC-SCs interacted with newly-growing host axons, while NCSCs showed better survival rate and distribution. The transplanted NCSCs mainly differentiated into Schwann cells with no te...
PLoS ONE, 2011
BORIS (CTCFL) is the paralog of CTCF (CCCTC-binding factor; NM_006565), a ubiquitously expressed ... more BORIS (CTCFL) is the paralog of CTCF (CCCTC-binding factor; NM_006565), a ubiquitously expressed DNA-binding protein with diverse roles in gene expression and chromatin organisation. BORIS and CTCF have virtually identical zinc finger domains, yet display major differences in their respective C-and N-terminal regions. Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a ''cancer-testis'' antigen. However, the expression pattern of BORIS is both a significant and unresolved question in the field of DNA binding proteins. Here, we identify BORIS in the cytoplasm and nucleus of a wide range of normal and cancer cells. We compare the localization of CTCF and BORIS in the nucleus and demonstrate enrichment of BORIS within the nucleolus, inside the nucleolin core structure and adjacent to fibrillarin in the dense fibrillar component. In contrast, CTCF is not enriched in the nucleolus. Live imaging of cells transiently transfected with GFP tagged BORIS confirmed the nucleolar accumulation of BORIS. While BORIS transcript levels are low compared to CTCF, its protein levels are readily detectable. These findings show that BORIS expression is more widespread than previously believed, and suggest a role for BORIS in nucleolar function.
Current Stem Cell Research & Therapy, 2009
Stem cell therapy has a place for future application in the treatment of degenerative diseases. R... more Stem cell therapy has a place for future application in the treatment of degenerative diseases. Regardless of the origin of the stem cell, when placed within a milieu of inflammatory mediator, they will show varied functions. This review focuses on human mesenchymal stem cells (MSCs) and discusses neuronal replacement using multi-and interdisciplinary approaches. We caution the enthusiasm of scientists since there is always the potential for tumor formation, even for adult stem cells. The review places RE-1 silencing transcription factor (REST) gene as central to the understanding of stem cell behavior in the microenvironment of tissue injury. REST is relevant in the development of dopaminergic and peptidergic neurons from MSCs. Premature downregulation of REST by the pro-inflammatory mediator, IL-1 , can prematurely lead to the expression of neurotransmitters, which in turn, could develop rapid crosstalk with immune cells. In-depth inter-and multidisciplinary research will lead to rapid and safe translation of MSCs to patients. An understanding of the changes induced in MSCs by cytokines and other mediators will establish future application of MSCs and other stem cells for safe and effective treatments. This study also alludes to the potential of personalized medicine through engineering and mathematics.
Current Pharmacogenomics and Personalized Medicine, 2011
Bone marrow transplantation is a form of cell therapy that has been in practice for decades for t... more Bone marrow transplantation is a form of cell therapy that has been in practice for decades for the treatment of hematological disorders and solid tumors. Immunosuppressive therapy has been a mainstay for treatment, but the severity of the adverse effects has made it an undesirable choice. Mesenchymal stem cells (MSCs), which reside in the vascular regions of the bone marrow, have been shown to serve as cellular support for the hematopoietic stem cell (HSC) niche. Furthermore, the immune suppressive properties of MSCs have been explored in the treatment of inflammatory and autoimmune disorders. Thus, co-therapy with MSCs has been shown to facilitate engraftment of hematopoietic cells by suppressive graft versus host disease (GvHD). Although the mechanism by which MSCs suppress GvHD is unclear, the experimental evidence suggests that this partly occurs by modulation of immune response such as the induction of regulatory T cells. This paper discusses the role of MSCs as co-therapy for the future of stem cell transplantation, with the overarching theme of personalized medicine for cell-based health interventions.
Genes & …, 2007
Autophagy is a catabolic process involving self-digestion of cellular organelles during starvatio... more Autophagy is a catabolic process involving self-digestion of cellular organelles during starvation as a means of cell survival; however, if it proceeds to completion, autophagy can lead to cell death. Autophagy is also a haploinsufficient tumor suppressor mechanism for mammary tumorigenesis, as the essential autophagy regulator beclin1 is monoallelically deleted in breast carcinomas. However, the mechanism by which autophagy suppresses breast cancer remains elusive. Here we show that allelic loss of beclin1 and defective autophagy sensitized mammary epithelial cells to metabolic stress and accelerated lumen formation in mammary acini. Autophagy defects also activated the DNA damage response in vitro and in mammary tumors in vivo, promoted gene amplification, and synergized with defective apoptosis to promote mammary tumorigenesis. Therefore, we propose that autophagy limits metabolic stress to protect the genome, and that defective autophagy increases DNA damage and genomic instability that ultimately facilitate breast cancer progression.
Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engin... more Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering.
Alzheimer's & Dementia, 2006
Recently, a single nucleotide polymorphism (rs699947) within the promoter of the Vascular Endothe... more Recently, a single nucleotide polymorphism (rs699947) within the promoter of the Vascular Endothelial Growth Factor (VEGF) gene has been reported to be associated with the risk of developing AD in an Italian population (Del bo et al., Ann Neurol. 2005;57:373-80). To validate this observation, we assessed the impact of this SNP on the risk of developing AD in a large French case-control population (respectively nϭ630 and nϭ664). We also evaluated its association with the severity of vascular lesions (arteriosclerosis, white matter loss and cerebral amyloid angiopathy) in AD brains (nϭ76). No association of this SNP with the risk of developing AD was observed (ORϭ1.1, 95% CI [0.9-1.4], pϽ0.39 adjusted on age and gender). No relationship between this SNP and vascular lesions in AD was detected. We next focused on the MEOX2 gene coding for a transcriptional factor involved in vascular differentiation and strongly under-expressed in AD brain endothelial cells (Wu et al., Nat Med. 2005;11:959-65). We analyzed the association of 4 SNPs with the risk of developing AD in a sub-population obtained by drawing lots from our large French case-control population (respectively, nϭ223 and nϭ265). No association was found whatever the studied SNPs. Furthermore, the haplotype distribution did not differ between the AD cases and control sub-populations.