Education & Training
- MD, University of Liverpool
- PhD, University of Louisville
- MRCSEd (Member of the Royal College of Surgeons of Edinburgh)
Representative Publications
Research Interests
Dr. Scott's research interests involve investigating innate immune responses after surgery, trauma, hemorrhagic shock and infection. Her main research focus is the role of the inflammasome and inflammatory caspases on cell death and survival pathways during surgery and trauma. This work centers on elucidation of novel pathways of inflammasome activation and function in the liver, and how mitochondria are central to these responses in both sterile and infectious tissue injury. She is also very interested in the different ways inflammasomes are activated in multiple cell types in a cell type-specific manner and how these varying responses help coordinate inflammatory responses to host stress and infection. She is also working on a project that investigates the role of pattern recognition receptors, danger signals and inflammasomes in models of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Dr. Scott has multiple collaborations with other PIs in the department, within the university and also at other instituations, which allows her to work on the role of inflammasomes in varying model systems such as tick-borne Ehrlichia infection (a collaboration with Dr. Nahed Ismail in the Department of Pathology), and sickle cell disease (a collaboration with Dr. Prithu Sundd in the Vascular Medicine Insititute).
As a post-doctoral research associate, I investigated the role of the pattern recognition receptor TLR4 on endotoxin uptake and clearance by the liver; this work is continuing. Dr. Scott's lab is now uncovering exciting findings suggesting cell-specific roles for TLR4 on endotoxin homeostasis during sepsis. Her PhD research investigated the role of natural killer and natural killer T-cells in the initiation of immune responses to sepsis, and she has since continued these studies in a model of hemorrhagic shock.
Dr. Scott is also involved with research investigating roles for damage associated molecular patterns (DAMPs) during trauma and infection. This work is being undertaken in the Billiar Lab in collaboration with multiple other labs both at Pitt/UPMC and at outside institutions.
The role of the inflammasome and caspase-1 in trauma and hemorrhage
Caspase-1 is an important enzyme in inflammatory processes with a main function of cleaving pro-forms of inflammatory cytokines IL-1beta and IL-18, which allows them to be released from macrophages and other immune cells. A lot less is known about the role of caspase-1 in non-immune cells such as hepatocytes, the main cell-type in the liver. These cells have been shown to activate caspase-1 but produce little if any IL-1beta or IL-18. Our lab is therefore focusing on identifying the function of caspase-1 activation in non-immune cells during global ischemia-reperfusion and oxidative stress induced by hemorrhagic shock and trauma.
We are also investigating how caspase-1 is activated in non-immune cells in our models. Caspase-1 is activated/cleaved through the activation of a group of proteins that form a platform known as the inflammasome. Multiple types of inflammasome have been described all of which include NOD-like proteins such as NLRP3 and NLRP1. Our lab is working to determine which mechanism of caspase-1 activation is important in end-organs such as the liver during hemorrhagic shock and after trauma. Understanding how the mechanisms behind the immune response to hemorrhage and trauma could identify novel future treatments for these patients and prevent morbidity and mortality from organ failure.
The role of the inflammasome and caspase-1 in sepsis
Proinflammatory cytokines, such as IL-1beta, are known to be extremely important in helping to activate immune responses to fight infection and clear bacteria from the blood and organs. However, too much inflammation can be damaging to cells and tissues, and can lead to organ dysfunction and failure. We are intersted in the role of the inflammasome and caspase-1 in initiating the immune response to surgical infection, and how responses are integrated between immune cells and end organs in order to clear bacteria and resolve infection.
The main model we are using is a model of polymicrobial peritonitis induced by ligating and punturing the cecum to release fecal bacteria into the abdomen. This model of cecal ligation and puncture (CLP) mimics many types of surgical abdominal infection such as a burst appendix or diveticulum and so is relevant to human disease. Understanding how the immune response is regulated by the inflammasome and caspase-1 may provide us with clues about new treatments that may help more effectively treat surgical patients in the future.
Inflammasome activation and metabolic control in the liver and during surgery
The inflammasome and its activation have been strongly implicated in the regulation of many metabolic events, including obesity-induced diabetes and insulin resistance. As the population of the United States as a whole becomes more obese it becomes more important for us to understand how the immune system is affected in these patients and how this affects both elective and emergency surgical outcomes. Our lab is interested in investigating the role of the inflammasome and caspase-1 particularly in the liver of obese subjects, and how the inflammasome affects immune processes that can regulate wound healing, inflammation and infection after hemorrhagic shock and trauma.