Melanie J. Scott, MD, PhD

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 the 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.  Dr. Scott is also involved with research investigating roles for damage associated molecular patterns (DAMPs) during trauma and infection. The research projects performed in Scott's lab are:

Caspase-1, caspase-11 and inflammasome activation in hemorrhagic shock and trauma: R01-funded project that focuses on inflammasome and inflammatory caspase activation in non-immune cells, especially hepatocytes during hypoxia/reoxygenation such as after hemorrhagic shock and traumatic injury. We have uncovered novel pathways of activation and novel effects of inflammasome activation in hemorrhagic shock, and this is associated with subsequent mortality and multiple organ failure in mouse models. This project also has a focus on cell death pathways initiated by inflammation.

Caspase-4/11 activation and cell death in sepsis: NIH funded project looking at activation of caspase-11 (or caspase-4 in humans) in models of polymicrobial sepsis, such as cecal ligation and puncture (CLP). Caspase-11 was recently identifies as the intracellular receptor for LPS, and we have shown signaling contributes to mortality and organ damage in mouse CLP. We have recently uncovered important pathways linking caspase-11 activaiton in the liver with release of inflammatory mediators such as HMGB1.

DAMP activation of immune responses in trauma: Damage-associated molecular patterns (DAMPs) have been shown to activate many pattern recognition receptors, including TLRs and NLRs and are therefore linked with inflammasome and innate immune activation, as well as mechanisms of cell death. This project is ongoing and in collaboration with multiple other PIs, including Dr. Jie Fan (member of PTRC).

Effect of Inflammasome activation in platelets: This project aims to assess the role of inflammasome activation in multiple diseases, including Sickle Cell Disease, trauma/hemorrhagic shock, sepsis and also in venous thromboembolism (VTE). These projects are in conjunction with Dr. Mackie Neal (Co-director of PTRC), Dr. Prithu Sundd (VMI) and Dr. Anirban Sen Gupta (Case Western University). Of particular interest is the role of platelet extracellular vesicles (microparticles/ exosomes), which are released after inflammasome/caspase-1 activation, and mediate effects of platelet-derived IL1b.

The role of innate immunity in Ehrlichia infection: Ehrlichia is a tick-borne obligate intracellular bacterium causing ehrlichiosis, and emerging tick-borne pathogen that causes liver damage and organ failure in humans. This project investigates the role of inflammasome-mediated pathways and their activation by pattern-associated molecular patterns (PAMPs) and DAMPs in the liver during Ehrlichia infection. This is an ongoing collaboration with Dr. Nahed Ismail at University of Illinois, Chicago.