Projects
Brain injury in sepsis survivors
Brain injury in sepsis survivors
Sepsis is a severe and life-threatening organ dysfunction caused by dysregulated response to infection. Patients who survive sepsis are at an increased risk for mood disorders and cognitive impairment. What are the mechanisms driving this brain dysfunction?
Sepsis is a severe and life-threatening organ dysfunction caused by dysregulated response to infection. Patients who survive sepsis are at an increased risk for mood disorders and cognitive impairment. What are the mechanisms driving this brain dysfunction?
Using mouse models and human tissues, our lab takes a combination of genetic, pharmacological, immunologic, and behavioral approaches to investigate changes to the neuroimmune system after sepsis.
Using mouse models and human tissues, our lab takes a combination of genetic, pharmacological, immunologic, and behavioral approaches to investigate changes to the neuroimmune system after sepsis.
Sepsis results in long-term reprogramming of the neuroimmune response. Some of these changes include increased expression of molecules that sustain the immune response such as cytokines, complement system proteins, and damage associated molecular patterns (DAMPs). In addition to these sepsis-driven changes, we are interested in how infection interacts with other factors that can make the brain more vulnerable to injury, such as vascular impairment, individual differences, and Alzheimer's disease pathology.
Sepsis results in long-term reprogramming of the neuroimmune response. Some of these changes include increased expression of molecules that sustain the immune response such as cytokines, complement system proteins, and damage associated molecular patterns (DAMPs). In addition to these sepsis-driven changes, we are interested in how infection interacts with other factors that can make the brain more vulnerable to injury, such as vascular impairment, individual differences, and Alzheimer's disease pathology.
Finally, we are exploring whether immunomodulation can break this cycle of neuroinflammation to improve the quality of life of sepsis survivors.
Finally, we are exploring whether immunomodulation can break this cycle of neuroinflammation to improve the quality of life of sepsis survivors.
Vulnerability to lung injury after sepsis
Vulnerability to lung injury after sepsis
One in 10 sepsis survivors will experience an episode of recurrent lung injury. How do long term changes in the immune response in sepsis survivors change vulnerability to lung injury after recurrent infection or sterile insults, like aspiration pneumonitis?
One in 10 sepsis survivors will experience an episode of recurrent lung injury. How do long term changes in the immune response in sepsis survivors change vulnerability to lung injury after recurrent infection or sterile insults, like aspiration pneumonitis?
Body composition, fatty liver disease and vulnerability to steatohepatitis after sepsis
Body composition, fatty liver disease and vulnerability to steatohepatitis after sepsis
Obesity induced by high fat diet is known to impair immune responses to infection, yet obese patients have improved outcomes after critical illness. Severe infections typically result in weight loss, but whether this weight loss improves metabolism or is injurious is poorly understood.
Obesity induced by high fat diet is known to impair immune responses to infection, yet obese patients have improved outcomes after critical illness. Severe infections typically result in weight loss, but whether this weight loss improves metabolism or is injurious is poorly understood.
We have found that in a mouse model of diet induced obesity, surviving pneumonia results in impaired ability of the liver to generate glucose and also results in a state of persistent liver inflammation that lasts for weeks. In a separate model of fatty liver disease, surviving pneumonia also resulted in persistent liver inflammation and increased liver fibrosis. Ongoing studies are examining the changes in macrophage phenotype induced by pneumonia and how these change the trajectory of liver fibrosis.
We have found that in a mouse model of diet induced obesity, surviving pneumonia results in impaired ability of the liver to generate glucose and also results in a state of persistent liver inflammation that lasts for weeks. In a separate model of fatty liver disease, surviving pneumonia also resulted in persistent liver inflammation and increased liver fibrosis. Ongoing studies are examining the changes in macrophage phenotype induced by pneumonia and how these change the trajectory of liver fibrosis.
Leveraging next-generation diagnostic platforms to increase the rigor of studies in critical illness
Leveraging next-generation diagnostic platforms to increase the rigor of studies in critical illness
In collaboration with the laboratory of Katsuo Kurabayashi (University of Michigan and New York University) we are leveraging ultra-sensitive and rapid digital ELISA assays to improve our understanding of how individual variation in host response may predict or shape long term outcomes such as brain injury and behavior. The long term goal of this work is to predict outcomes in both humans and mice, and make real-time treatment decisions early in the disease course to optimize the study of disease-modifying treatments in sepsis.
In collaboration with the laboratory of Katsuo Kurabayashi (University of Michigan and New York University) we are leveraging ultra-sensitive and rapid digital ELISA assays to improve our understanding of how individual variation in host response may predict or shape long term outcomes such as brain injury and behavior. The long term goal of this work is to predict outcomes in both humans and mice, and make real-time treatment decisions early in the disease course to optimize the study of disease-modifying treatments in sepsis.
We are grateful for the support of:
National Institute for Neurologic Disorders and Stroke
National Heart, Lung and Blood Institute
American Thoracic Society
Central Society for Clinical and Translational Research
Michigan Depression Center
Michigan Alzheimer's Disease Research Center