Szabo Lab

BIDMC
Funding
The overall goal of this research is to define molecular mechanisms that regulate the switch from the acute, anti-inflammatory to the chronic, pro-inflammatory effects of alcohol.
This application further investigates if the absence of TLR4, but not of the MyD88 adaptor, protects mice from alcoholic liver disease.
Experiments proposed in this supplement will explore novel signaling molecules in alcohol-induced neuroinflammation and interactions between alcohol use and key pathways in the biology of neuroinflammation and AD dementia. Our studies will reveal new potential therapeutic targets in the dual insult of alcohol use and Alzheimer’s disease on the brain and dementias.
The Alcoholic Hepatitis Network project, AlcHepNet, comprised of nine leading partner institutions in the field, will examine new and promising treatments for severe liver damage caused by alcohol. Further, the network will collect and organize patient information, associated data, and samples that can help shed greater light on this disease. Combined, these two approaches will improve treatment and how we care for patients with this devastating liver condition.
This translational research study will utilize clinical information and biospecimens collected in the AlcHepNet clinical trials from subjects with alcoholic hepatitis and control groups. Our aim is to characterize immune abnormalities in AH that contribute to infection, sepsis, and organ failure. We will also test the biological effect of novel therapies on biomarkers of inflammation, gut permeability, and liver regeneration.
This translational research project will evaluate the utility of extracellular vesicles for biomarker discovery in alcoholic hepatitis to provide better tools for clinicians on predicting clinical outcomes and better understand the natural history of the disease. Exploration of the specific protein and RNA cargo in these extracellular vesicles will discover candidate biomarkers that will be validated in large patient cohorts.
This research will test new cellular mechanisms in ALD such as autophagy and exosome production and their regulation by microRNA-155, a non-coding RNA, to discover how to liver cell damage and inflammation occur. Our research will identify and test candidate molecules for novel interventions in the mouse model of ALD using gene therapy approaches that will provide basis for future studies in patients with alcoholic hepatitis.
The proposed experiments will provide several novel findings related to alcohol-induced neuroinflammation and on interactions between alcohol use and key pathways in the biology of neuroinflammation and AD dementia. Our studies will reveal new potential therapeutic targets in the dual insult of alcohol use and Alzheimer’s Disease on the brain and dementias.