Melanie J Scott, MD, PhD
Research Assistant Professor and Director of Graduate Education for Surgical Research
Dr. Scott is a Research Assistant Professor and Director of Graduate Education for Surgical Research, Department of Surgery.
3459 Fifth Ave.
Pittsburgh PA 15213
Office Telephone: 412-647-5806
- MD - 1996, University of Liverpool, UK
- MRCSEd - 2000, Member of the Royal College of Surgeons of Edinburgh, UK
- PhD - 2003, University of Louisville, KY
Research InterestsMy research interests mainly involve assessing innate immune responses after surgery, trauma, hemorrhagic shock and infection. I have recently become interested in the role of the inflammasome and inflammatory caspases on cell death and survival pathways during surgery and trauma. This work focuses on novel pathways of activation of autophagy in the liver and the removal of damaged mitochondria. This is now my main research focus and represents the overall direction of my future research as a principal investigator.
As a post-doctoral research associate I mainly investigated 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 the department of Surgery in collaboration with multiple other labs both at Pitt/UPMC and at outside institutions.
- Sun Q, Gao W, Loughran P, Shapiro R, Fan J, Billiar TR, Scott MJ. Caspase-1 activation is protective against hepatocyte cell death by up-regulating beclin1 and mitochondrial autophagy in the setting of redox stress. J Biol Chem. 2013 May 31;288(22):15947-58. doi: 10.1074/jbc.M112.426791. Epub 2013 Apr 15. PubMed PMID: 23589298. PMCID: PMC3668750.
- Chen C, Deng M, Sun Q, Loughran P, Billiar TR, Scott MJ. Lipopolysaccharide stimulates p62-dependent autophagy-like aggregate clearance in hepatocytes. BioMed Res Internat. 2014;2014:267350. PMID: 24683544 PMCID: PMC3934718
- Yang Q, Stevenson HL, Scott MJ, Ismail N. Type I interferon contributes to noncanonical inflammasome activation, mediates immunopathology, and impairs protective immunity during fatal infection with lipopolysaccharide-negative Ehrlichiae. Am J Pathol. 2014 Dec 3. pii: S0002-9440(14)00597-5. doi: 10.1016/j.ajpath.2014.10.005. [Epub ahead of print] PMID: 25481711
- Deng M, Loughran P, Zhang L, Scott MJ, Billiar TR. Hepatocyte-TNFR1 shedding limits excessive inflammation during sepsis via MyD88-iNOS-cGMP-TACE-dependent signaling. Sci Signal. 2014 In Press
- Seymour CW, Yende S, Scott MJ, Pribis JP, Mohney RP, Bell LN, Chen YF, Zuckerbraun BS, Bigbee WH, Yealy DM, Weissfeld L, Kellum J, Angus DC. Metabolomics in pneumonia and sepsis: an analysis of the GenIMS cohort study. Intensive Care Med. 2013 May 15. [Epub ahead of print]. PubMed PMID: 23673400
- Deng M, Scott MJ, Loughran P, Gibson G, Sodhi C, Watkins S, Hackam D, Billiar TR. Lipopolysaccharide clearance, bacterial clearance and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis. J Immunol. 2013 May 15;190(10):5152-60. doi: 10.4049/jimmunol.1300496. Epub 2013 Apr 5. PubMed PMID: 23562812. PMCID: PMC3644895.
- Menzel CL, Sun Q, Loughran PA, Pape HC, Billiar TR, Scott MJ. Caspase-1 is hepatoprotective during trauma and hemorrhagic shock in mice by reducing liver injury and inflammation. Mol Med. 2011 Sep-Oct;17(9-10):1031-8. doi: 10.2119/molmed.2011.00015. Epub 2011 Jun 7. PubMed PMID: 21666957. PMCID: PMC3188860.