Sarah Y Yuan

Research topics

Matched from this investigator's NIH project titles and abstracts.

• Traumatic Brain Injury
• PTSD and Trauma
• Developmental Cognitive Neuroscience

Active NIH awards

• Vascular Barrier Leakage in Inflammation

  5R35HL150732-06

  NHLBI · FY 2025 · $894K

  PROJECT SUMMARY/ABSTRACT Vascular barrier dysfunction causes aberrant transport of blood components into the vessel wall or surrounding tissues, a hallmark of inflammatory injury in response to trauma, sepsis, atherosclerosis, diabetes, and stroke. Currently, there are no effective therapies that directly target the leaky barrier, as drug development has been hampered by knowledge gaps and difficulties in translating cell/animal data to human pathophysiology. Our program addresses these challenges via comparative analyses of endothelial barrier structure and function in human and animal models of inflammatory injury. We conduct three series of studies in the blood, blood-vessel interface and endothelial barrier structure, aimed at 1) identifying key circulating factors that cause barrier leakage and their cell-specific mechanisms of production and action; 2) characterizing endothelial surface receptors and intracellular signals that transduce their effects; and 3) elucidating molecular events in cell-cell junctions, cytoskeleton, and glycocalyx that ultimately lead to barrier opening. Our work has continuously been supported by the NHLBI contributing to the development of novel techniques and transformative theories in vascular permeability. We were among the first to characterize the nmMLCK signaling in endothelial junction dynamics and paracellular permeability during leukocyte activation. Recently, we reported the discovery of a new post-translational modification pathway, dhhc21-mediated protein palmitoylation, in microvascular leakage and leukocyte-endothelium interactions following infection and sterile injury. Built on these exciting findings, our program continues to advance by exploring novel diagnostic/therapeutic targets with mechanistic insights that will transform the paradigm of inflammation. Current efforts are directed to the characterization of neutrophil extracellular traps, histones and microvesicles, focusing on their cell-specific mechanisms of generation and function in the microcirculation. Studies are on-going to test the roles of palmitoylation in vesicle biogenesis, cargo composition and interaction with endothelial cells. The barrier-disrupting effects of these factors will be uncovered with in-depth molecular details on endothelial glycocalyx receptors, intracellular signal transduction, and post-translational modification (palmitoylation) of junction structures. We use a multifaceted approach that incorporates innovative molecular biology and imaging techniques (many developed in our lab) into functional analyses of vascular permeability under clinically relevant conditions. Complementary in vitro, ex vivo, and in vivo experiments are designed testing pharmacological activators and inhibitors, molecular manipulations, and genetic/chimeric alterations at cell-tissue-body levels. A unique aspect of our program lies in the translational impact achieved through the studies with intact functionally viable human organs.

• Endothelial glycocalyx shedding in septic injury

  5R01GM142110-04

  NIGMS · FY 2025 · $467K

  PROJECT SUMMARY/ABSTRACT Sepsis is a critical illness arising from dysregulated host response to infection where invading pathogens elicit an adverse systemic inflammatory response that affects multiple organs and tissues. Currently, there are limited therapies that effectively treat this disease. The overarching goal of our work is to identify new molecular targets that can potentially serve as diagnostics or therapeutics for prevention and treatment of sepsis. This project focuses on glycocalyx shedding as not merely a consequence, but a critical cause, of inflammatory injury. Specifically, we hypothesize that bacterial infection promotes disintegrin metalloprotease (ADAM) upregulation and activity to shed glycocalyx molecules on endothelial surface and release their fragments into the circulation, which act as inflammatory signals to mediate microcirculatory dysfunction and barrier leakage by triggering endothelial cytoskeleton-junction responses. This novel concept will be tested by completing two aims: Aim 1 to characterize the molecular property of glycocalyx shedding products and function in microvascular inflammation during sepsis; Aim 2 to elucidate the molecular mechanisms of endothelial glycocalyx shedding and barrier injury. We propose a multifaceted approach based on an innovative design that integrates peptidomics, proteomics and nanotechnology with multispectral photoacoustic tomography, super-resolution confocal and 3D intravital microscopic imaging. Functionally viable human lungs and microvessels serve as the primary models, which are complemented by animal models and cell experiments. Microvascular barrier structure and function will be examined in-depth at the organ, tissue and cell levels under pathophysiologically relevant conditions of bacterial infection. We expect to gain novel insights that will not only fill the knowledge gaps in understanding the molecular mechanisms of septic injury, but also contribute to the development of effective therapeutics against infectious diseases. The proposed human organ studies further highlight the translational values of our work.

• Training in Research on Vascular Inflammation and Injury

  5T32HL160529-04

  NHLBI · FY 2025 · $296K

  This program is designed to train pre- and postdoctoral scientists in basic and translational research, focusing on vascular inflammation and associated disease or injury in the heart, brain, lung, kidney, gut, and placenta. As all tissues are connected via blood vessels and lymphatics, inflammatory responses in the circulation play a central role in the onset and progression of multiple organ dysfunction and pathologies, including hypertension, atherosclerosis, arrythmia, myocardium infarction, acute respiratory distress syndrome, stroke, preeclampsia, neurodegenerative disorder, traumatic brain injury, and sepsis. The recent discovery of vasculitis as a leading cause of mortality and morbidity in patients with pneumonia and sepsis further accentuates the need for future research to decipher molecular/cellular mechanisms and identify diagnostic/therapeutic targets for vascular inflammation. The goal of this program is to provide comprehensive training in research focusing on the molecular and cellular basis of inflammation and related organ injury, taking advantage of our faculty's nationally recognized expertise in inflammation research and vascular biology. The mentoring faculty consist of 20 mentors from 7 departments across 6 inter-departmental programs or research centers, 7 of whom hold MD/PhD degrees and 4 are practicing physicians; all have been funded by the NIH and have extensive experience in mentoring at both pre- and postdoctoral levels. The group has already established a close collaborative relationship in research and training, evidenced by co-mentorship for graduate students, co-authorship in numerous publications and presentations, and joint effort in grant applications. The proximity of their laboratories, along with the centralized administrative support provided by the department chaired by the program director, further enables close mentor-mentee interactions. Trainees will be selected from a large pool of PhD candidates and postgraduates in basic science programs, as well as 14 medical residency/fellowship programs related to cardiovascular sciences. The program design includes a comprehensive set of training modalities, featuring a rigorous curriculum composed of didactic courses and workshops to build knowledge and competency, an intensive research project emphasizing hands-on experience and critical/innovative thinking, and a personalized development plan to equip the trainees with not only workplace survival skills but also the vision and capability to lead independent research. Trainees will be immersed in a highly collaborative environment supported by substantial institutional resources committed to the Heart Institute, Neuroscience Institute, full-spectrum core services, bridge funding for faculty mentors, and tuition waiver and stipend supplement for trainees. In addition, the program offers several unique opportunities for trainees to learn techniques and experimental approaches that are not commonly available elsewhere, including 3/4D intravital microscopic/molecular imaging in the blood and lymph microvasculature, and translational studies using intact, functionally viable human organs.

• Vascular Barrier Leakage in Inflammation

  5R35HL150732-05

  NHLBI · FY 2024 · $876K

  PROJECT SUMMARY/ABSTRACT Vascular barrier dysfunction causes aberrant transport of blood components into the vessel wall or surrounding tissues, a hallmark of inflammatory injury in response to trauma, sepsis, atherosclerosis, diabetes, and stroke. Currently, there are no effective therapies that directly target the leaky barrier, as drug development has been hampered by knowledge gaps and difficulties in translating cell/animal data to human pathophysiology. Our program addresses these challenges via comparative analyses of endothelial barrier structure and function in human and animal models of inflammatory injury. We conduct three series of studies in the blood, blood-vessel interface and endothelial barrier structure, aimed at 1) identifying key circulating factors that cause barrier leakage and their cell-specific mechanisms of production and action; 2) characterizing endothelial surface receptors and intracellular signals that transduce their effects; and 3) elucidating molecular events in cell-cell junctions, cytoskeleton, and glycocalyx that ultimately lead to barrier opening. Our work has continuously been supported by the NHLBI contributing to the development of novel techniques and transformative theories in vascular permeability. We were among the first to characterize the nmMLCK signaling in endothelial junction dynamics and paracellular permeability during leukocyte activation. Recently, we reported the discovery of a new post-translational modification pathway, dhhc21-mediated protein palmitoylation, in microvascular leakage and leukocyte-endothelium interactions following infection and sterile injury. Built on these exciting findings, our program continues to advance by exploring novel diagnostic/therapeutic targets with mechanistic insights that will transform the paradigm of inflammation. Current efforts are directed to the characterization of neutrophil extracellular traps, histones and microvesicles, focusing on their cell-specific mechanisms of generation and function in the microcirculation. Studies are on-going to test the roles of palmitoylation in vesicle biogenesis, cargo composition and interaction with endothelial cells. The barrier-disrupting effects of these factors will be uncovered with in-depth molecular details on endothelial glycocalyx receptors, intracellular signal transduction, and post-translational modification (palmitoylation) of junction structures. We use a multifaceted approach that incorporates innovative molecular biology and imaging techniques (many developed in our lab) into functional analyses of vascular permeability under clinically relevant conditions. Complementary in vitro, ex vivo, and in vivo experiments are designed testing pharmacological activators and inhibitors, molecular manipulations, and genetic/chimeric alterations at cell-tissue-body levels. A unique aspect of our program lies in the translational impact achieved through the studies with intact functionally viable human organs.

• Training in Research on Vascular Inflammation and Injury

  5T32HL160529-03

  NHLBI · FY 2024 · $368K

  This program is designed to train pre- and postdoctoral scientists in basic and translational research, focusing on vascular inflammation and associated disease or injury in the heart, brain, lung, kidney, gut, and placenta. As all tissues are connected via blood vessels and lymphatics, inflammatory responses in the circulation play a central role in the onset and progression of multiple organ dysfunction and pathologies, including hypertension, atherosclerosis, arrythmia, myocardium infarction, acute respiratory distress syndrome, stroke, preeclampsia, neurodegenerative disorder, traumatic brain injury, and sepsis. The recent discovery of vasculitis as a leading cause of mortality and morbidity in patients with COVID-19 further accentuates the need for future research to decipher molecular/cellular mechanisms and identify diagnostic/therapeutic targets for vascular inflammation. The goal of this program is to provide comprehensive training in research focusing on the molecular and cellular basis of inflammation and related organ injury, taking advantage of our faculty's nationally recognized expertise in inflammation research and vascular biology. The mentoring faculty consist of 20 mentors from 7 departments across 6 inter-departmental programs or research centers, 7 of whom hold MD/PhD degrees and 4 are practicing physicians; all have been funded by the NIH and have extensive experience in mentoring at both pre- and postdoctoral levels. The group has already established a close collaborative relationship in research and training, evidenced by co-mentorship for graduate students, co-authorship in numerous publications and presentations, and joint effort in grant applications. The proximity of their laboratories, along with the centralized administrative support provided by the department chaired by the program director, further enables close mentor-mentee interactions. Trainees will be selected from a large pool of PhD candidates and postgraduates in basic science programs, as well as 14 medical residency/fellowship programs related to cardiovascular sciences. A significant portion (up to 27%) of trainees come from underrepresented racial/ethnic groups or with socioeconomically disadvantaged backgrounds. The program design includes a comprehensive set of training modalities, featuring a rigorous curriculum composed of didactic courses and workshops to build knowledge and competency, an intensive research project emphasizing hands-on experience and critical/innovative thinking, and a personalized development plan to equip the trainees with not only workplace survival skills but also the vision and capability to lead independent research. Trainees will be immersed in a highly collaborative environment supported by substantial institutional resources committed to the Heart Institute, Neuroscience Institute, full-spectrum core services, bridge funding for faculty mentors, and tuition waiver and stipend supplement for trainees. In addition, the program offers several unique opportunities for trainees to learn techniques and experimental approaches that are not commonly available elsewhere, including 3/4D intravital microscopic/molecular imaging in the blood and lymph microvasculature, and translational studies using intact, functionally viable human organs.

• Vascular Barrier Leakage in Inflammation

  5R35HL150732-04

  NHLBI · FY 2023 · $894K

  PROJECT SUMMARY/ABSTRACT Vascular barrier dysfunction causes aberrant transport of blood components into the vessel wall or surrounding tissues, a hallmark of inflammatory injury in response to trauma, sepsis, atherosclerosis, diabetes, and stroke. Currently, there are no effective therapies that directly target the leaky barrier, as drug development has been hampered by knowledge gaps and difficulties in translating cell/animal data to human pathophysiology. Our program addresses these challenges via comparative analyses of endothelial barrier structure and function in human and animal models of inflammatory injury. We conduct three series of studies in the blood, blood-vessel interface and endothelial barrier structure, aimed at 1) identifying key circulating factors that cause barrier leakage and their cell-specific mechanisms of production and action; 2) characterizing endothelial surface receptors and intracellular signals that transduce their effects; and 3) elucidating molecular events in cell-cell junctions, cytoskeleton, and glycocalyx that ultimately lead to barrier opening. Our work has continuously been supported by the NHLBI contributing to the development of novel techniques and transformative theories in vascular permeability. We were among the first to characterize the nmMLCK signaling in endothelial junction dynamics and paracellular permeability during leukocyte activation. Recently, we reported the discovery of a new post-translational modification pathway, dhhc21-mediated protein palmitoylation, in microvascular leakage and leukocyte-endothelium interactions following infection and sterile injury. Built on these exciting findings, our program continues to advance by exploring novel diagnostic/therapeutic targets with mechanistic insights that will transform the paradigm of inflammation. Current efforts are directed to the characterization of neutrophil extracellular traps, histones and microvesicles, focusing on their cell-specific mechanisms of generation and function in the microcirculation. Studies are on-going to test the roles of palmitoylation in vesicle biogenesis, cargo composition and interaction with endothelial cells. The barrier-disrupting effects of these factors will be uncovered with in-depth molecular details on endothelial glycocalyx receptors, intracellular signal transduction, and post-translational modification (palmitoylation) of junction structures. We use a multifaceted approach that incorporates innovative molecular biology and imaging techniques (many developed in our lab) into functional analyses of vascular permeability under clinically relevant conditions. Complementary in vitro, ex vivo, and in vivo experiments are designed testing pharmacological activators and inhibitors, molecular manipulations, and genetic/chimeric alterations at cell-tissue-body levels. A unique aspect of our program lies in the translational impact achieved through the studies with intact functionally viable human organs.

• Training in Research on Vascular Inflammation and Injury

  5T32HL160529-02

  NHLBI · FY 2023 · $278K

  This program is designed to train pre- and postdoctoral scientists in basic and translational research, focusing on vascular inflammation and associated disease or injury in the heart, brain, lung, kidney, gut, and placenta. As all tissues are connected via blood vessels and lymphatics, inflammatory responses in the circulation play a central role in the onset and progression of multiple organ dysfunction and pathologies, including hypertension, atherosclerosis, arrythmia, myocardium infarction, acute respiratory distress syndrome, stroke, preeclampsia, neurodegenerative disorder, traumatic brain injury, and sepsis. The recent discovery of vasculitis as a leading cause of mortality and morbidity in patients with COVID-19 further accentuates the need for future research to decipher molecular/cellular mechanisms and identify diagnostic/therapeutic targets for vascular inflammation. The goal of this program is to provide comprehensive training in research focusing on the molecular and cellular basis of inflammation and related organ injury, taking advantage of our faculty's nationally recognized expertise in inflammation research and vascular biology. The mentoring faculty consist of 20 mentors from 7 departments across 6 inter-departmental programs or research centers, 7 of whom hold MD/PhD degrees and 4 are practicing physicians; all have been funded by the NIH and have extensive experience in mentoring at both pre- and postdoctoral levels. The group has already established a close collaborative relationship in research and training, evidenced by co-mentorship for graduate students, co-authorship in numerous publications and presentations, and joint effort in grant applications. The proximity of their laboratories, along with the centralized administrative support provided by the department chaired by the program director, further enables close mentor-mentee interactions. Trainees will be selected from a large pool of PhD candidates and postgraduates in basic science programs, as well as 14 medical residency/fellowship programs related to cardiovascular sciences. A significant portion (up to 27%) of trainees come from underrepresented racial/ethnic groups or with socioeconomically disadvantaged backgrounds. The program design includes a comprehensive set of training modalities, featuring a rigorous curriculum composed of didactic courses and workshops to build knowledge and competency, an intensive research project emphasizing hands-on experience and critical/innovative thinking, and a personalized development plan to equip the trainees with not only workplace survival skills but also the vision and capability to lead independent research. Trainees will be immersed in a highly collaborative environment supported by substantial institutional resources committed to the Heart Institute, Neuroscience Institute, full-spectrum core services, bridge funding for faculty mentors, and tuition waiver and stipend supplement for trainees. In addition, the program offers several unique opportunities for trainees to learn techniques and experimental approaches that are not commonly available elsewhere, including 3/4D intravital microscopic/molecular imaging in the blood and lymph microvasculature, and translational studies using intact, functionally viable human organs.

Earlier awards

• Endothelial glycocalyx shedding in septic injuryFY 2024 · $466K
• Endothelial glycocalyx shedding in septic injuryFY 2023 · $466K