Yao Yao
Principal Investigator (NIH-funded) · PHYSIOLOGY · USF
Affiliated program: Neuroscience PhD
This profile was assembled automatically from NIH RePORTER award records. Department and program affiliations are inferred and may be out of date — confirm on the university website.
Funding summary
- Active NIH grants
- 7
- Total NIH funding
- $3.5M
- Award records
- 7
Research topics
Matched from this investigator's NIH project titles and abstracts.
Active NIH awards
The roles of pericyte-derived laminin in neurovascular function and neurodegeneration
5R01AG065345-03NIA · FY 2025 · $608K
Project Summary/Abstract The long-term objective of this application is to understand whether the basement membrane (BM), the non-cellular component of the neurovascular unit, is involved in the pathogenesis of Alzheimer’s disease and can be targeted to treat Alzheimer’s disease and Alzheimer’s disease-related dementias. This is consistent with the mission of NIA. This proposal aims to investigate the biological functions of pericytic laminin in: (1) neurovascular function, including blood brain barrier (BBB) integrity, cerebral blood flow (CBF) and brain influx/efflux function, and (2) neuronal survival/function. In Aim 1, the function of pericytic laminin in BBB integrity will be investigated. First, whether and to what extent loss of pericytic laminin affects BBB integrity will be investigated using FITC-Dextrans of various molecular weights (Aim 1A). Next, the molecular mechanism underlying loss of pericytic laminin-induced BBB breakdown will be investigated, with a focus on changes in paracellular and transcellular transport in endothelial cells (Aim 1B). Furthermore, the receptors that mediate pericytic laminin’s effect in endothelial cells will be identified and examined (Aim 1C). In Aim 2, the function of pericytic laminin in CBF will be investigated. First, how loss of pericytic laminin affects CBF will be investigated using quantitative autoradiography and two-photon imaging (Aim 2A). Next, whether the reduced CBF is caused by pericyte loss/degeneration will be investigated in vitro and in vivo (Aim 2B). Furthermore, the receptors that mediate pericytic laminin’s effect in pericytes will be identified and examined (Aim 2C). In Aim 3, the role of pericytic laminin in brain influx/efflux function will be investigated. First, whether and how loss of pericytic laminin affects brain influx/efflux function will be investigated by influx/efflux assays using various fluorescently labeled macromolecules (Aim 3A). Next, whether the impaired influx/efflux function is due to BM damage and how loss of pericytic laminin affects BM composition/structure will be explored (Aim 3B). In Aim 4, the function of pericytic laminin in neuronal injury/neurodegeneration will be investigated. In this aim, whether loss of pericytic laminin leads to neuronal injury/neurodegeneration will be investigated at biochemical, structural, and functional levels. In addition, the age at which neuronal injury/neurodegeneration occurs will be determined and compared to that at which neurovascular dysfunction occurs. Successful completion of this study will elucidate the fundamental roles of pericytic laminin in neurovascular function and neuronal survival/function, and identify novel molecular targets with therapeutic potential in Alzheimer’s disease and Alzheimer’s disease-related dementias. In addition, this proposal may also lead to the generation of an innovative mouse model for neurodegeneration and open doors for new research.
Fibroblast-derived laminin regulates blood-brain barrier integrity and fibroblast biology in hemorrhagic brain
5R01NS134134-03NINDS · FY 2025 · $494K
Project Summary/Abstract The long-term objective of this application is to develop innovative therapies for intracerebral hemorrhage (ICH), which causes high rates of death and disability worldwide. This is consistent with the mission of NINDS. This proposal aims to investigate the biological functions of fibroblast-derived laminin in blood-brain barrier (BBB) repair and fibroblast biology after ICH and explore the underlying molecular mechanisms. In Aim 1, the function of fibroblast-derived laminin in ICH pathogenesis will be investigated in two clinically relevant ICH models using middle-aged transgenic mice with laminin deficiency in fibroblasts. In Aim 2, the function of fibroblast-derived laminin in BBB repair after ICH will be investigated both in vitro and in vitro. First, how loss of fibroblast-derived laminin affects BBB permeability and inflammatory cell infiltration after ICH will be examined (Aim 2A). Next, whether loss of fibroblast-derived laminin exacerbates BBB disruption via paracellular and/or transcellular mechanisms will be investigated (Aim 2B). Third, the receptors that mediate fibroblast-derived laminin’s “BBB-repairing” effect on endothelial cells will be identified using both pharmacological and genetic approaches (Aim 2C). In Aim 3, the function of fibroblast-derived laminin in fibroblast biology and fibrotic scar composition will be investigated. First, fibroblast biology (proliferation/apoptosis/migration), fibroblast morphology, and fibrotic scar components will be examined in vitro and in vivo (Aim 3A). Next, how exactly fibroblast-derived laminin regulates fibroblast biology and fibrotic scar composition will be explored by bulk and/or single-cell RNAseq analysis (Aim 3B). Third, the receptors that mediate these changes in fibroblasts will be identified using both pharmacological and genetic approaches (Aim 3C). Successful completion of this proposal will elucidate novel functions of fibroblast-derived laminin in BBB repair and fibroblast biology after ICH, identify the receptors that mediate these effects on both endothelial cells and fibroblasts, provide new molecular targets with therapeutic potential, and promote the development of innovative and effective treatments for ICH.
Brain extracellular matrix changes during normal aging and in Alzheimer disease
1R21AG091884-01A1NIA · FY 2025 · $413K
Project Summary/Abstract The long-term objective of this application is to identify novel biomarkers for early diagnosis and/or prognosis prediction of Alzheimer’s disease (AD), a neurodegenerative disorder that affects 5.5 million people in the US. This is consistent with the mission of NIA. This proposal aims to determine brain extracellular matrix (ECM) composition changes during normal aging and in AD in both rodents and humans using an innovative decellularization-based proteomic approach. In Aim 1, Mouse ECM composition in different brain regions and at various ages will be determined using an innovative decellularization-based proteomic approach optimized in our laboratory. In Aim 2, brain ECM composition changes in both 5xFAD and PS19 mouse models of AD will be investigated similarly. Different brain regions and various ages (representing distinct stages of AD) will be analyzed to determine any region-specific and age-dependent changes. In Aim 3, ECM composition alterations in human AD brains will be explored using postmortem prefrontal cortex samples from AD patients and age/gender-matched controls. In addition, the contributions of CAA (a vascular pathology frequently found in AD brains) and ApoE4 (a major genetic risk factor for AD) in ECM composition will be determined by including samples with and without CAA and ApoE4 in each condition. Successful completion of this study will establish ECM composition in mouse brains in a region-specific manner, elucidate ECM changes during normal aging, characterize the temporary and spatial changes of the ECM in two mouse models of AD, and determine ECM alterations in AD patients. These findings will provide a comprehensive picture on how each ECM protein changes during normal aging and in AD in any brain region at any time, which will pave the way for future research and substantially move the field forward. This proposal may lead to the identification of novel biomarkers in early AD diagnosis and/or prognosis prediction.
The roles of pericyte-derived laminin in neurovascular function and neurodegeneration
4R01AG065345-02NIA · FY 2024 · $613K
Project Summary/Abstract The long-term objective of this application is to understand whether the basement membrane (BM), the non-cellular component of the neurovascular unit, is involved in the pathogenesis of Alzheimer’s disease and can be targeted to treat Alzheimer’s disease and Alzheimer’s disease-related dementias. This is consistent with the mission of NIA. This proposal aims to investigate the biological functions of pericytic laminin in: (1) neurovascular function, including blood brain barrier (BBB) integrity, cerebral blood flow (CBF) and brain influx/efflux function, and (2) neuronal survival/function. In Aim 1, the function of pericytic laminin in BBB integrity will be investigated. First, whether and to what extent loss of pericytic laminin affects BBB integrity will be investigated using FITC-Dextrans of various molecular weights (Aim 1A). Next, the molecular mechanism underlying loss of pericytic laminin-induced BBB breakdown will be investigated, with a focus on changes in paracellular and transcellular transport in endothelial cells (Aim 1B). Furthermore, the receptors that mediate pericytic laminin’s effect in endothelial cells will be identified and examined (Aim 1C). In Aim 2, the function of pericytic laminin in CBF will be investigated. First, how loss of pericytic laminin affects CBF will be investigated using quantitative autoradiography and two-photon imaging (Aim 2A). Next, whether the reduced CBF is caused by pericyte loss/degeneration will be investigated in vitro and in vivo (Aim 2B). Furthermore, the receptors that mediate pericytic laminin’s effect in pericytes will be identified and examined (Aim 2C). In Aim 3, the role of pericytic laminin in brain influx/efflux function will be investigated. First, whether and how loss of pericytic laminin affects brain influx/efflux function will be investigated by influx/efflux assays using various fluorescently labeled macromolecules (Aim 3A). Next, whether the impaired influx/efflux function is due to BM damage and how loss of pericytic laminin affects BM composition/structure will be explored (Aim 3B). In Aim 4, the function of pericytic laminin in neuronal injury/neurodegeneration will be investigated. In this aim, whether loss of pericytic laminin leads to neuronal injury/neurodegeneration will be investigated at biochemical, structural, and functional levels. In addition, the age at which neuronal injury/neurodegeneration occurs will be determined and compared to that at which neurovascular dysfunction occurs. Successful completion of this study will elucidate the fundamental roles of pericytic laminin in neurovascular function and neuronal survival/function, and identify novel molecular targets with therapeutic potential in Alzheimer’s disease and Alzheimer’s disease-related dementias. In addition, this proposal may also lead to the generation of an innovative mouse model for neurodegeneration and open doors for new research.
Fibroblast-derived laminin regulates blood-brain barrier integrity and fibroblast biology in hemorrhagic brain
5R01NS134134-02NINDS · FY 2024 · $479K
Project Summary/Abstract The long-term objective of this application is to develop innovative therapies for intracerebral hemorrhage (ICH), which causes high rates of death and disability worldwide. This is consistent with the mission of NINDS. This proposal aims to investigate the biological functions of fibroblast-derived laminin in blood-brain barrier (BBB) repair and fibroblast biology after ICH and explore the underlying molecular mechanisms. In Aim 1, the function of fibroblast-derived laminin in ICH pathogenesis will be investigated in two clinically relevant ICH models using middle-aged transgenic mice with laminin deficiency in fibroblasts. In Aim 2, the function of fibroblast-derived laminin in BBB repair after ICH will be investigated both in vitro and in vitro. First, how loss of fibroblast-derived laminin affects BBB permeability and inflammatory cell infiltration after ICH will be examined (Aim 2A). Next, whether loss of fibroblast-derived laminin exacerbates BBB disruption via paracellular and/or transcellular mechanisms will be investigated (Aim 2B). Third, the receptors that mediate fibroblast-derived laminin’s “BBB-repairing” effect on endothelial cells will be identified using both pharmacological and genetic approaches (Aim 2C). In Aim 3, the function of fibroblast-derived laminin in fibroblast biology and fibrotic scar composition will be investigated. First, fibroblast biology (proliferation/apoptosis/migration), fibroblast morphology, and fibrotic scar components will be examined in vitro and in vivo (Aim 3A). Next, how exactly fibroblast-derived laminin regulates fibroblast biology and fibrotic scar composition will be explored by bulk and/or single-cell RNAseq analysis (Aim 3B). Third, the receptors that mediate these changes in fibroblasts will be identified using both pharmacological and genetic approaches (Aim 3C). Successful completion of this proposal will elucidate novel functions of fibroblast-derived laminin in BBB repair and fibroblast biology after ICH, identify the receptors that mediate these effects on both endothelial cells and fibroblasts, provide new molecular targets with therapeutic potential, and promote the development of innovative and effective treatments for ICH.
Fibroblast-derived laminin regulates blood-brain barrier integrity and fibroblast biology in hemorrhagic brain
1R01NS134134-01NINDS · FY 2023 · $490K
Project Summary/Abstract The long-term objective of this application is to develop innovative therapies for intracerebral hemorrhage (ICH), which causes high rates of death and disability worldwide. This is consistent with the mission of NINDS. This proposal aims to investigate the biological functions of fibroblast-derived laminin in blood-brain barrier (BBB) repair and fibroblast biology after ICH and explore the underlying molecular mechanisms. In Aim 1, the function of fibroblast-derived laminin in ICH pathogenesis will be investigated in two clinically relevant ICH models using middle-aged transgenic mice with laminin deficiency in fibroblasts. In Aim 2, the function of fibroblast-derived laminin in BBB repair after ICH will be investigated both in vitro and in vitro. First, how loss of fibroblast-derived laminin affects BBB permeability and inflammatory cell infiltration after ICH will be examined (Aim 2A). Next, whether loss of fibroblast-derived laminin exacerbates BBB disruption via paracellular and/or transcellular mechanisms will be investigated (Aim 2B). Third, the receptors that mediate fibroblast-derived laminin’s “BBB-repairing” effect on endothelial cells will be identified using both pharmacological and genetic approaches (Aim 2C). In Aim 3, the function of fibroblast-derived laminin in fibroblast biology and fibrotic scar composition will be investigated. First, fibroblast biology (proliferation/apoptosis/migration), fibroblast morphology, and fibrotic scar components will be examined in vitro and in vivo (Aim 3A). Next, how exactly fibroblast-derived laminin regulates fibroblast biology and fibrotic scar composition will be explored by bulk and/or single-cell RNAseq analysis (Aim 3B). Third, the receptors that mediate these changes in fibroblasts will be identified using both pharmacological and genetic approaches (Aim 3C). Successful completion of this proposal will elucidate novel functions of fibroblast-derived laminin in BBB repair and fibroblast biology after ICH, identify the receptors that mediate these effects on both endothelial cells and fibroblasts, provide new molecular targets with therapeutic potential, and promote the development of innovative and effective treatments for ICH.
Earlier awards
- Endothelial laminin in blood brain barrier regulationFY 2023 · $375K