Haoyu Chen | Renmin University of China (original) (raw)
Papers by Haoyu Chen
Advances in Experimental Medicine and Biology, 2009
Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the cen... more Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the central nervous system. Intense investigation found that this pathway also plays an important role in other biological process including angiogenesis. Robo4 is the vascular endothelial cell specific member of Robo family. It was found that Slit-Robo signaling can inhibit endothelial cell migration, tube formation and vascular permeability. Slit-Robo signaling also plays an important role in embryonic and tumor angiogenesis. In animal model of ocular angiogenesis, addition of Slit inhibited laser induced choroidal neovascularization, oxygen induced retinopathy and VEGF induced retinal permeability in a Robo4 dependent manner. Recent data demonstrates that Robo1 and Robo4 form a heterodimer in endothelial cells, The role of this heterodimer in counteracting VEGF signaling is unknown. Further investigation is required to better understand Slit-Robo signaling and develop novel therapy for angiogenesis.
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ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011
ABSTRACT Intracranial aneurysms appear as sac-like outpouchings of the cerebral vasculature wall;... more ABSTRACT Intracranial aneurysms appear as sac-like outpouchings of the cerebral vasculature wall; inflated by the pressure of the blood that fills them. They are relatively common and affect up to 5% of the adult population. Fortunately, most remain asymptomatic. However, there is a small but inherent risk of rupture: 0.1% to 1% of detected aneurysms rupture every year. If rupture does occur there is a 30% to 50% chance of fatality. Consequently, if an aneurysm is detected, clinical intervention may be deemed appropriate. Therapy is currently aimed at pre-rupture detection and preventative treatment. However, interventional procedures are not without risk to the patient. The improvement and optimization of interventional techniques is an important concern for patient welfare and is necessary for rationalisation of healthcare priorities. Hence there is a need to develop methodologies to assist in identifying those ICAs most at risk of rupture. We focus on the mathematical modelling and computational simulation of ICA evolution. Models must take into consideration: (i) the biomechanics of the arterial wall; (ii) the biology of the arterial wall and (iii) the complex interplay between (i) and (ii), i.e. the mechanobiology of the arterial wall. The ultimate ambition of such models is to aid clinical diagnosis on a patient-specific basis. However, due to the significant biological complexity coupled with limited histological information such models are still in their relative infancy. Current research focuses on simulating the evolution of an ICA with an aim to yield insight into the growth and remodelling (G&R) processes that give rise to inception, enlargement, stabilisation and rupture. We present a novel Fluid-Structure-Growth computational framework for modelling aneurysm evolution.
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Current Diabetes Reports, 2008
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Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the cen... more Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the central nervous system. Intense investigation found that this pathway also plays an important role in other biological process including angiogenesis. Robo4 is the vascular endothelial cell specific member of Robo family. It was found that Slit-Robo signaling can inhibit endothelial cell migration, tube formation and vascular permeability. Slit-Robo signaling also plays an important role in embryonic and tumor angiogenesis. In animal model of ocular angiogenesis, addition of Slit inhibited laser induced choroidal neovascularization, oxygen induced retinopathy and VEGF induced retinal permeability in a Robo4 dependent manner. Recent data demonstrates that Robo1 and Robo4 form a heterodimer in endothelial cells, The role of this heterodimer in counteracting VEGF signaling is unknown. Further investigation is required to better understand Slit-Robo signaling and develop novel therapy for angiogenesis.
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Current Diabetes Reports, 2008
Diabetes continues to be a major source of morbidity and mortality among working-age adults natio... more Diabetes continues to be a major source of morbidity and mortality among working-age adults nationally and internationally. The microvascular complications of diabetes, including diabetic retinopathy, account for a major proportion of disease-associated morbidity and likely contribute to macrovascular complications. Although glycemic control contributes to susceptibility for diabetic complications, some people with strict control develop these complications, whereas others with poor control remain complication free. This suggests a genetic contribution to disease development. Although many genes and proteins of vascular growth have been studied in association with diabetic retinopathy, no definitive major predisposing genes or functional consequences of genetic variants have been identified for microvascular complications of the disease. In this article, we review the studies done on candidate genes.
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Advances in Experimental Medicine and Biology, 2008
Age-related macular degeneration (AMD) includes a wide range of phenotypes. Early AMD is mainly c... more Age-related macular degeneration (AMD) includes a wide range of phenotypes. Early AMD is mainly characterized by the presence of soft dusen in the macula without visual loss, while advanced AMD is characterized by geographic atrophy (GA or dry AMD) and neovascular AMD (wet ...
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Vision research, 2008
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PLoS genetics, 2010
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Nature Medicine, 2008
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Vision Research, 2007
ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM ... more ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM 600110.) To date, three ELOVL4 mutations have been identified, all of which result in truncated proteins which induce autosomal dominant juvenile macular degenerations. Based on sequence homology, ELOVL4 is thought to be another member within a family of proteins functioning in the elongation of long chain fatty acids. However, the normal function of ELOVL4 is unclear. We generated Elovl4 knockout mice to determine if Elovl4 loss affects retinal development or function. Here we show that Elovl4 knockout mice, while perinatal lethal, exhibit normal retinal development prior to death at day of birth. Further, postnatal retinal development in Elovl4 heterozygous mice appears normal. Therefore haploinsufficiency for wildtype ELOVL4 in autosomal dominant macular degeneration likely does not contribute to juvenile macular degeneration in STGD3 patients. We found, however, that Elovl4+/- mice exhibit enhanced ERG scotopic and photopic a and b waves relative to wildtype Elovl4+/+ mice suggesting that reduced Elovl4 levels may impact retinal electrophysiological responses.
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Journal of Colloid and Interface Science, 2001
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Journal of Clinical Investigation, 2009
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Science, 2005
We report a regime of ion beam sputtering that occurs for sufficiently steep slopes. High slopes ... more We report a regime of ion beam sputtering that occurs for sufficiently steep slopes. High slopes propagate over large distances without dissipating the steepest features. Both the propagation velocity and the dynamically selected slope are universal, independent of the details of the initial shape of the surface. The resulting behavior can be understood as the propagation of a shock front that self-selects a stable slope, as has been previously observed in thin-film fluid flows. Experiments confirm predictions of the theory. An important implication of the propagative behavior at high surface slopes is that a pattern can be fabricated at a large length scale and, through uniform ion irradiation, reduced to a smaller length scale while preserving, or even sharpening, the sharpest features.
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Vision Research, 2008
We examined familial aggregation and risk of age-related macular degeneration in the Utah populat... more We examined familial aggregation and risk of age-related macular degeneration in the Utah population using a population-based case-control study. Over one million unique patient records were searched within the University of Utah Health Sciences Center and the Utah Population Database (UPDB), identifying 4764 patients with AMD. Specialized kinship analysis software was used to test for familial aggregation of disease, estimate the magnitude of familial risks, and identify families at high risk for disease. The population-attributable risk (PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate increased relative risks in siblings (2.95), first cousins (1.29), second cousins (1.13), and parents (5.66) of affected cases. There were 16 extended large families with AMD identified for potential use in genetic studies. Each family had five or more living affected members. The familial aggregation of AMD shown in this study exemplifies the merit of the UPDB and supports recent research demonstrating significant genetic contribution to disease development and progression.
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Proceedings of The National Academy of Sciences, 2008
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Vision Research, 2007
ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM ... more ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM 600110.) To date, three ELOVL4 mutations have been identified, all of which result in truncated proteins which induce autosomal dominant juvenile macular degenerations. Based on sequence homology, ELOVL4 is thought to be another member within a family of proteins functioning in the elongation of long chain fatty acids. However, the normal function of ELOVL4 is unclear. We generated Elovl4 knockout mice to determine if Elovl4 loss affects retinal development or function. Here we show that Elovl4 knockout mice, while perinatal lethal, exhibit normal retinal development prior to death at day of birth. Further, postnatal retinal development in Elovl4 heterozygous mice appears normal. Therefore haploinsufficiency for wildtype ELOVL4 in autosomal dominant macular degeneration likely does not contribute to juvenile macular degeneration in STGD3 patients. We found, however, that Elovl4+/− mice exhibit enhanced ERG scotopic and photopic a and b waves relative to wildtype Elovl4+/+ mice suggesting that reduced Elovl4 levels may impact retinal electrophysiological responses.
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Cell Cycle, 2008
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Advances in Experimental Medicine and Biology, 2009
Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the cen... more Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the central nervous system. Intense investigation found that this pathway also plays an important role in other biological process including angiogenesis. Robo4 is the vascular endothelial cell specific member of Robo family. It was found that Slit-Robo signaling can inhibit endothelial cell migration, tube formation and vascular permeability. Slit-Robo signaling also plays an important role in embryonic and tumor angiogenesis. In animal model of ocular angiogenesis, addition of Slit inhibited laser induced choroidal neovascularization, oxygen induced retinopathy and VEGF induced retinal permeability in a Robo4 dependent manner. Recent data demonstrates that Robo1 and Robo4 form a heterodimer in endothelial cells, The role of this heterodimer in counteracting VEGF signaling is unknown. Further investigation is required to better understand Slit-Robo signaling and develop novel therapy for angiogenesis.
Bookmarks Related papers MentionsView impact
ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011
ABSTRACT Intracranial aneurysms appear as sac-like outpouchings of the cerebral vasculature wall;... more ABSTRACT Intracranial aneurysms appear as sac-like outpouchings of the cerebral vasculature wall; inflated by the pressure of the blood that fills them. They are relatively common and affect up to 5% of the adult population. Fortunately, most remain asymptomatic. However, there is a small but inherent risk of rupture: 0.1% to 1% of detected aneurysms rupture every year. If rupture does occur there is a 30% to 50% chance of fatality. Consequently, if an aneurysm is detected, clinical intervention may be deemed appropriate. Therapy is currently aimed at pre-rupture detection and preventative treatment. However, interventional procedures are not without risk to the patient. The improvement and optimization of interventional techniques is an important concern for patient welfare and is necessary for rationalisation of healthcare priorities. Hence there is a need to develop methodologies to assist in identifying those ICAs most at risk of rupture. We focus on the mathematical modelling and computational simulation of ICA evolution. Models must take into consideration: (i) the biomechanics of the arterial wall; (ii) the biology of the arterial wall and (iii) the complex interplay between (i) and (ii), i.e. the mechanobiology of the arterial wall. The ultimate ambition of such models is to aid clinical diagnosis on a patient-specific basis. However, due to the significant biological complexity coupled with limited histological information such models are still in their relative infancy. Current research focuses on simulating the evolution of an ICA with an aim to yield insight into the growth and remodelling (G&R) processes that give rise to inception, enlargement, stabilisation and rupture. We present a novel Fluid-Structure-Growth computational framework for modelling aneurysm evolution.
Bookmarks Related papers MentionsView impact
Current Diabetes Reports, 2008
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Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the cen... more Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the central nervous system. Intense investigation found that this pathway also plays an important role in other biological process including angiogenesis. Robo4 is the vascular endothelial cell specific member of Robo family. It was found that Slit-Robo signaling can inhibit endothelial cell migration, tube formation and vascular permeability. Slit-Robo signaling also plays an important role in embryonic and tumor angiogenesis. In animal model of ocular angiogenesis, addition of Slit inhibited laser induced choroidal neovascularization, oxygen induced retinopathy and VEGF induced retinal permeability in a Robo4 dependent manner. Recent data demonstrates that Robo1 and Robo4 form a heterodimer in endothelial cells, The role of this heterodimer in counteracting VEGF signaling is unknown. Further investigation is required to better understand Slit-Robo signaling and develop novel therapy for angiogenesis.
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Current Diabetes Reports, 2008
Diabetes continues to be a major source of morbidity and mortality among working-age adults natio... more Diabetes continues to be a major source of morbidity and mortality among working-age adults nationally and internationally. The microvascular complications of diabetes, including diabetic retinopathy, account for a major proportion of disease-associated morbidity and likely contribute to macrovascular complications. Although glycemic control contributes to susceptibility for diabetic complications, some people with strict control develop these complications, whereas others with poor control remain complication free. This suggests a genetic contribution to disease development. Although many genes and proteins of vascular growth have been studied in association with diabetic retinopathy, no definitive major predisposing genes or functional consequences of genetic variants have been identified for microvascular complications of the disease. In this article, we review the studies done on candidate genes.
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Advances in Experimental Medicine and Biology, 2008
Age-related macular degeneration (AMD) includes a wide range of phenotypes. Early AMD is mainly c... more Age-related macular degeneration (AMD) includes a wide range of phenotypes. Early AMD is mainly characterized by the presence of soft dusen in the macula without visual loss, while advanced AMD is characterized by geographic atrophy (GA or dry AMD) and neovascular AMD (wet ...
Bookmarks Related papers MentionsView impact
Vision research, 2008
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PLoS genetics, 2010
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Nature Medicine, 2008
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Vision Research, 2007
ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM ... more ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM 600110.) To date, three ELOVL4 mutations have been identified, all of which result in truncated proteins which induce autosomal dominant juvenile macular degenerations. Based on sequence homology, ELOVL4 is thought to be another member within a family of proteins functioning in the elongation of long chain fatty acids. However, the normal function of ELOVL4 is unclear. We generated Elovl4 knockout mice to determine if Elovl4 loss affects retinal development or function. Here we show that Elovl4 knockout mice, while perinatal lethal, exhibit normal retinal development prior to death at day of birth. Further, postnatal retinal development in Elovl4 heterozygous mice appears normal. Therefore haploinsufficiency for wildtype ELOVL4 in autosomal dominant macular degeneration likely does not contribute to juvenile macular degeneration in STGD3 patients. We found, however, that Elovl4+/- mice exhibit enhanced ERG scotopic and photopic a and b waves relative to wildtype Elovl4+/+ mice suggesting that reduced Elovl4 levels may impact retinal electrophysiological responses.
Bookmarks Related papers MentionsView impact
Journal of Colloid and Interface Science, 2001
Bookmarks Related papers MentionsView impact
Journal of Clinical Investigation, 2009
Bookmarks Related papers MentionsView impact
Science, 2005
We report a regime of ion beam sputtering that occurs for sufficiently steep slopes. High slopes ... more We report a regime of ion beam sputtering that occurs for sufficiently steep slopes. High slopes propagate over large distances without dissipating the steepest features. Both the propagation velocity and the dynamically selected slope are universal, independent of the details of the initial shape of the surface. The resulting behavior can be understood as the propagation of a shock front that self-selects a stable slope, as has been previously observed in thin-film fluid flows. Experiments confirm predictions of the theory. An important implication of the propagative behavior at high surface slopes is that a pattern can be fabricated at a large length scale and, through uniform ion irradiation, reduced to a smaller length scale while preserving, or even sharpening, the sharpest features.
Bookmarks Related papers MentionsView impact
Vision Research, 2008
We examined familial aggregation and risk of age-related macular degeneration in the Utah populat... more We examined familial aggregation and risk of age-related macular degeneration in the Utah population using a population-based case-control study. Over one million unique patient records were searched within the University of Utah Health Sciences Center and the Utah Population Database (UPDB), identifying 4764 patients with AMD. Specialized kinship analysis software was used to test for familial aggregation of disease, estimate the magnitude of familial risks, and identify families at high risk for disease. The population-attributable risk (PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate increased relative risks in siblings (2.95), first cousins (1.29), second cousins (1.13), and parents (5.66) of affected cases. There were 16 extended large families with AMD identified for potential use in genetic studies. Each family had five or more living affected members. The familial aggregation of AMD shown in this study exemplifies the merit of the UPDB and supports recent research demonstrating significant genetic contribution to disease development and progression.
Bookmarks Related papers MentionsView impact
Proceedings of The National Academy of Sciences, 2008
Bookmarks Related papers MentionsView impact
Vision Research, 2007
ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM ... more ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM 600110.) To date, three ELOVL4 mutations have been identified, all of which result in truncated proteins which induce autosomal dominant juvenile macular degenerations. Based on sequence homology, ELOVL4 is thought to be another member within a family of proteins functioning in the elongation of long chain fatty acids. However, the normal function of ELOVL4 is unclear. We generated Elovl4 knockout mice to determine if Elovl4 loss affects retinal development or function. Here we show that Elovl4 knockout mice, while perinatal lethal, exhibit normal retinal development prior to death at day of birth. Further, postnatal retinal development in Elovl4 heterozygous mice appears normal. Therefore haploinsufficiency for wildtype ELOVL4 in autosomal dominant macular degeneration likely does not contribute to juvenile macular degeneration in STGD3 patients. We found, however, that Elovl4+/− mice exhibit enhanced ERG scotopic and photopic a and b waves relative to wildtype Elovl4+/+ mice suggesting that reduced Elovl4 levels may impact retinal electrophysiological responses.
Bookmarks Related papers MentionsView impact
Cell Cycle, 2008
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