Yao Yao

Research topics

Matched from indexed official interests or NIH project evidence.

• Alzheimer's and Dementia
• Developmental Cognitive Neuroscience
• Cognitive Aging

Active NIH awards

• Fibroblast-derived laminin regulates blood-brain barrier integrity and fibroblast biology in hemorrhagic brain

  5R01NS134134-03

  NINDS · 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

  1R21AG091884-01A1

  NIA · 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.

• Fibroblast-derived laminin regulates blood-brain barrier integrity and fibroblast biology in hemorrhagic brain

  5R01NS134134-02

  NINDS · 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

  1R01NS134134-01

  NINDS · 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 or dates unavailable

• The roles of pericyte-derived laminin in neurovascular function and neurodegenerationFY 2025 · $608K
• The roles of pericyte-derived laminin in neurovascular function and neurodegenerationFY 2024 · $613K
• Endothelial laminin in blood brain barrier regulationFY 2023 · $375K