Melanie J Scott, MD, PhD

Education

  • 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 Interests

My research interests focus on innate immune responses after surgery, trauma, hemorrhagic shock and infection. My main research interest is the role of the inflammasome and inflammatory caspases on organ injury, cell death and survival pathways, release of extracellular vesicles (EVs) including exosomes. I also have projects in collaboration with other investigators to look at O-GlcNAcylation of proteins in response to trauma and hemorrhage, as well as effects of inflammasomes on thrombosis and platelet aggregation during surgery and trauma. I am a member of the Pittsburgh Liver Research Center, as well as the Pittsburgh Trauma Research Center, which I collaborate widely with other faculty in the Department of Surgery, Vascular Medicine Institute, Critical Care Medicine, and Pathology at Pitt. I also have multiple collaborations with researchers across the US, including Chicago, Denver and Boston. These projects include studies into tick-borne infection/sepsis, intracranial hemorrhage, sickle cell disease and acute lung and liver injury.

I am actively looking for graduate students and post-docs to join my lab to focus on NIH funded projects investigating inflammasomes, platelets, and also sickle-cell induced lung injury.

 

Selected Publications

  1. Sun Q, Fan J, Billiar TR, Scott MJ. Inflammasome and autophagy regulation - a two-way street. Mol Med. 2017 Jul 24;23. doi: 10.2119/molmed.2017.00077. [Epub ahead of print] PMID: 28741645 PMCID: PMC5588408
  2. Zhou H, Deng M, Liu Y, Yang C, Hoffmann R, Zhou J, Loughran PA, Liao H, Scott MJ, Neal M, Billiar TR. Platelet HMGB1 is Required for Efficient Bacterial Clearance in Intra-abdominal Bacterial Sepsis. Blood Adv. 2018 Mar 27;2(6):638-648. doi:10.1182/bloodadvances.2017011 817. PMID: 29563120 PMCID: PMC5873229
  3. 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. PMID: 29511181 PMCID: PMC5840374
  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 Macrophage Exosome Release. Mil Med Res. 2018 Jul 30;5(1):24. PMID: 30056803 PMCID: PMC6065058
  5. 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 PMID: 30314759 PMCID: PMC6300139
  6. 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. J Immunol. 2018 Oct 15;201(8):2209-2214. doi: 10.4049/jimmunol.1800505. Epub 2018 Sep 12. PMID: 30209191 PMCID: PMC6176107
  7. Vats R, Brzoska T, Bennewitz MF, Jimenez MA, Pradhan-Sundd T, Tutuncuoglu E, Jonassaint J, Gutierrez E, Watkins SC, Shiva S, Scott MJ, Morelli AE, Neal MD, Kato GJ, Gladwin MT, Sundd P. Platelet extracellular vesicles drive inflammasome-IL1?-dependent lung injury in Sickle Cell Disease. Am J Respir Crit Care Med. 2020 Jan 1;201(1):33-46. doi: 10.1164/ rccm.201807-1370OC. PMID: 31498653; PMCID: PMC6938158.
  8. Yang C, Sun P, Deng M, Loughran P, Li W, Yi Z, Li S, Zhang X, Fan J, Billiar TR, Scott MJ. Gasdermin D protects against non-infectious liver injury by regulating apoptosis and necroptosis. Cell Death Dis 2019 Jun 17;10(7):481. PMID: 31209224 PMCID: PMC6579760
  9. Deng M, Scott MJ*, Fan J, Billiar TR. (*co-first author) Location is the key to function: HMGB1 in sepsis and trauma-induced inflammation. J Leukoc Biol. 2019 Jul;106(1):161-169. Epub 2019 Apr 4. Review. PMID: 30946496; PMCID: PMC6597316.
  10. Sobel ME, Dreyfus JC, Dillehay McKillip K, Kolarcik C, Muller WA, Scott MJ, Siegal G, Wadosky K, O'Leary T. Return of individual research results: a guide for biomedical researchers utilizing human biospecimens. Am J Pathol. 2020 May;190(5):918-933. doi: 10.1016/j.ajpath. 2020.01.014. Epub 2020 Mar 19.
  11. Yi Z, Deng M, Scott MJ, Loughran PA, Lei Z, Li S, Yang C, Li W, Xu H, Huang F, Billiar TR. IRG1/Itaconate Activates Nrf2 in Hepatocytes to Protect Against Liver Ischemia/Reperfusion Injury. Hepatology. 2020 Jan 30;. doi: 10.1002/hep.31147. [Epub ahead of print] PMID: 31997373.
  12. Li S, Yi Z, Deng M, Scott MJ, Yang C, Li W, Lei Z, Santerre NM, Loughran P, Billiar TR. TSLP protects against liver I/R injury via activation of the PI3K/Akt pathway. JCI Insight. 2019 Nov 14;4(22). doi: 10.1172/jci.insight.129013. PMID: 31723054; PMCID: PMC6948857.
  13. Li W, Deng M, Loughran P, Yang M, Lin M, Yang C, Gao W, Jin S, Li S, Cai J, Lu B, Billiar TR, Scott MJ. LPS induces HMGB1 release from hepatocytes into exosomes through the coordinated activities of TLR4 and caspase-11/GSDMD signaling. Front Immunol. 2020 Apr 3;11:229. PMID: 32328059; PMCID: PMC7160675