Melanie J. Scott, MD, PhD

  • Director of Graduate Education for Surgery Research
  • Associate Professor of Surgery

Education & Training

  • Graduate School – University of Louisville – PhD
  • Medical School – University of Liverpool, England - MD

Research Grants

NIH Grants:  R01

Research Summary

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. 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 institutions, 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).

Representative Publications

  1. Sun Q, Loughran P, Shapiro R, Shrivastava IH, Antoine DJ, Li T, Yan Z, Fan J, Billiar TR, Scott MJ. Redox-dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice. Hepatology. 2017 Jan;65(1):253-268. doi: 10.1002/hep.28893. Epub 2016 Nov 29. PubMed PMID: 27774630; PubMed Central PMCID: PMC5191963.
  2. Deng M, Tang Y, Li W, Wang X, Zhang R, Zhang X, Zhao X, Liu J, Tang C, Liu Z, Huang Y, Peng H, Xiao L, Tang D, Scott MJ, Wang Q, Liu J, Xiao X, Watkins S, Li J, Yang H, Wang H, Chen F, Tracey KJ, Billiar TR, Lu B. The Endotoxin Delivery Protein HMGB1 Mediates Caspase-11-Dependent Lethality in Sepsis. Immunity. 2018 Oct 16;49(4):740-753.e7. doi: 10.1016/j.immuni.2018.08.016. Epub 2018 Oct 9. PubMed PMID: 30314759.
  3. Wang Y, Sedlacek AL, Pawaria S, Xu H, Scott MJ, Binder RJ. Cutting Edge: The Heat Shock Protein gp96 Activates Inflammasome-Signaling Platforms in APCs. J Immunol. 2018 Oct 15;201(8):2209-2214. doi: 10.4049/jimmunol.1800505. Epub 2018 Sep 12. PubMed PMID: 30209191; PubMed Central PMCID: PMC6176107.
  4. Li ZG, Scott MJ, Brzóska T, Sundd P, Li YH, Billiar TR, Wilson MA, Wang P, Fan J. Lung epithelial cell-derived IL-25 negatively regulates LPS-induced exosome release from macrophages. Mil Med Res. 2018 Jul 30;5(1):24. doi: 10.1186/s40779-018-0173-6. PubMed PMID: 30056803; PubMed Central PMCID: PMC6065058.
  5. Zhou H, Deng M, Liu Y, Yang C, Hoffman R, Zhou J, Loughran PA, Scott MJ, Neal MD, Billiar TR. Platelet HMGB1 is required for efficient bacterial clearance in intra-abdominal bacterial sepsis in mice. Blood Adv. 2018 Mar 27;2(6):638-648. doi: 10.1182/bloodadvances.2017011817. PubMed PMID: 29563120; PubMed Central PMCID: PMC5873229.
  6. Lai D, Tang J, Chen L, Fan EK, Scott MJ, Li Y, Billiar TR, Wilson MA, Fang X, Shu Q, Fan J. Group 2 innate lymphoid cells protect lung endothelial cells from pyroptosis in sepsis. Cell Death Dis. 2018 Mar 6;9(3):369. doi: 10.1038/s41419-018-0412-5. PubMed PMID: 29511181; PubMed Central PMCID: PMC5840374.
  7. Lei Z, Deng M, Yi Z, Sun Q, Shapiro RA, Xu H, Li T, Loughran PA, Griepentrog JE, Huang H, Scott MJ, Huang F, Billiar TR. cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING. Am J Physiol Gastrointest Liver Physiol. 2018 Jun 1;314(6):G655-G667. doi: 10.1152/ajpgi.00326.2017. Epub 2018 Feb 15. PubMed PMID: 29446653; PubMed Central PMCID: PMC6032062.
  8. Lin MJ, Dai W, Scott MJ, Li R, Zhang YQ, Yang Y, Chen LZ, Huang XS. Metformin improves nonalcoholic fatty liver disease in obese mice via down-regulation of apolipoprotein A5 as part of the AMPK/LXRα signaling pathway. Oncotarget. 2017 Oct 30;8(65):108802-108809. doi: 10.18632/oncotarget.22163. eCollection 2017 Dec 12. PubMed PMID: 29312569; PubMed Central PMCID: PMC5752482.
  9. Zettel K, Korff S, Zamora R, Morelli AE, Darwiche S, Loughran PA, Elson G, Shang L, Salgado-Pires S, Scott MJ, Vodovotz Y, Billiar TR. Toll-Like Receptor 4 on both Myeloid Cells and Dendritic Cells Is Required for Systemic Inflammation and Organ Damage after Hemorrhagic Shock with Tissue Trauma in Mice. Front Immunol. 2017 Nov 28;8:1672. doi: 10.3389/fimmu.2017.01672. eCollection 2017. PubMed PMID: 29234326; PubMed Central PMCID: PMC5712321.