Melanie J. Scott, MD, PhD
NW607 MUH, 3459 Fifth Ave
Research Assistant Professor and Director of Graduate Education for Surgery Labs
MD – Medicine - University of Liverpool, UK
PhD – Immunology - University of Louisville, KY, USA
MRCSEd – Member of the Royal College of Surgeons of Edinburgh
My research interests involve investigating innate immune responses after surgery, trauma, hemorrhagic shock and infection. My 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. I am 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. I am 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). I have multiple collaborations with other PIs in the department, within the university and also at other instituations, which allows me to work on the role of inflammasomes in varying model systems such as tick-borne Ehrlichia infection (a collaboration with Dr. Nahed Ismail in Pathology), and sickle cell disease (a collaboration with Dr. Prithu Sundd in the Vascular Medicine Insititute).
As a post-doctoral research associate I investigating the role of the pattern recognition receptor, TLR4, on endotoxin uptake and clearance by the liver and this work is continuing. We are now uncovering exciting findings suggesting cell-specific roles for TLR4 on endotoxin homeostasis during sepsis. My PhD research investigated the role of natural killer and natural killer T-cells in the initiation of immune responses to sepsis, and I have since continued these studies in a model of hemorrhagic shock.
I am 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.
Redox-dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice. Sun Q, Loughran P, Shapiro R, Shrivastava IH, Antoine DJ, Li T, Yan Z, Fan J, Billiar TR, Scott MJ. Hepatology. 2017 Jan;65(1):253-268. doi: 10.1002/hep.28893. PMID:27774630 | View publication
Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. Sun Q, Scott MJ. J Leukoc Biol. 2016 Nov;100(5):961-967. Review. PMID:27450556 | View publication
Tissue damage negatively regulates LPS-induced macrophage necroptosis. Li Z, Scott MJ, Fan EK, Li Y, Liu J, Xiao G, Li S, Billiar TR, Wilson MA, Jiang Y, Fan J. Cell Death Differ. 2016 Sep 1;23(9):1428-47. doi: 10.1038/cdd.2016.21. PMID:26943325 | View publication
Caspase 1 activation is protective against hepatocyte cell death by up-regulating beclin 1 protein and mitochondrial autophagy in the setting of redox stress. Sun Q, Gao W, Loughran P, Shapiro R, Fan J, Billiar TR, Scott MJ. J Biol Chem. 2013 May 31;288(22):15947-58. doi: 10.1074/jbc.M112.426791. PMID:23589298 | View publication
Caspase-1 is hepatoprotective during trauma and hemorrhagic shock by reducing liver injury and inflammation. Menzel CL, Sun Q, Loughran PA, Pape HC, Billiar TR, Scott MJ. Mol Med. 2011 17:1031-8. doi: 10.2119/molmed.2011.00015. Epub 2011 Jun 7. PMID: 21666957 | View Publication
Hepatocytes express functional NOD1 and NOD2 receptors: a role for NOD1 in hepatocyte CC and CXC chemokine production. Scott MJ, Chen C, Sun Q, Billiar TR. J Hepatol. 2010 53:693-701. Epub 2010 Jun 16. PMID: 20615568 | View Publication
Hemorrhagic shock activation of NLRP3 inflammasome in lung endothelial cells. Xiang M, Shi X, Li Y, Xu J, Yin L, Xiao G, Scott MJ, Billiar TR, Wilson MA, Fan J. J Immunol. 2011 187:4809-17. Epub 2011 Sep 21. PMID: 21940680 | View Publication
Endotoxin uptake in mouse liver is blocked by endotoxin pretreatment through a suppressor of cytokine signaling-1-dependent mechanism. Scott MJ, Liu S, Shapiro RA, Vodovotz Y, Billiar TR. Hepatology. 2009 49:1695-708. PMID: 19296467 | View Publication
Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14/TLR4/MD2-dependent uptake of lipopolysaccharide by hepatocytes. Scott MJ, Billiar TR. J Biol Chem. 2008 283:29433-46. Epub 2008 Aug 13. PMID:18701460 | View Publication