MSTPublications: April 2018
Congratulations to all of our MSTP students on their successful publications! Take a look at the great work our students are doing.
First Author Original Research:
Glucagon-like peptide-1 receptor signaling attenuates RSV-induced type 2 responses and immunopathology.
Bloodworth MH, Rusznak M, Pfister CC, Zhang J, Bastarache L, Calvillo SA, Chappell JD, Boyd KL, Toki S, Newcomb DC, Stier MT, Zhou W, Goleniewska K, Moore ML, Hartert TV, Niswender KD, Peebles RS Jr.
J Allergy Clin Immunol. 2018 Apr 17. pii: S0091-6749(18)30561-X. doi: 10.1016/j.jaci.2018.01.053. [Epub ahead of print]
Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalization and the second most frequent cause of “excess death” during winter months in elderly and high-risk adults. Severe RSV-associated illness is partially caused by type 2-associated immunopathology. We found that the emerging anti-inflammatory target, glucagon-like peptide 1 receptor (GLP-1R) signaling, attenuated type 2-associated immunopathology in mice infected with a strain of RSV that was isolated from a hospitalized infant with severe lower respiratory tract infection and bronchiolitis. The primary significance of our work is three-fold. First, our study identifies a GLP-1R agonist, a drug that is currently FDA-approved for type 2 diabetes, as a potential new treatment strategy for RSV bronchiolitis. This is of particular interest given our lack of therapeutic options to treat severe RSV disease, and since GLP-1R agonists have already shown promising initial results in clinical trials for the treatment of inflammatory diseases such as cardiovascular disease and psoriasis. Second, our report shows that a GLP-1R agonist inhibits IL-33 protein expression in a mouse model of RSV infection. IL-33 is a primary therapeutic target for inhibiting inflammatory lung disease given its central role in mediating both innate and adaptive immunity during lung inflammation. Finally, our study demonstrates an association between GLP-1R signaling and acute bronchiolitis in humans. Our study has broad implications for the fields of incretin biology and respiratory virology by highlighting the human relevance of GLP-1 signaling in bronchiolitis. This has critical relevance given the recent and growing interest in the use of GLP-1R agonists to improve inflammatory disease outcomes. (By Melissa Bloodworth, M3)
The TLR4 Agonist Monophosphoryl Lipid A Drives Broad Resistance to Infection via Dynamic Reprogramming of Macrophage Metabolism.
Fensterheim BA, Young JD, Luan L, Kleinbard RR, Stothers CL, Patil NK, McAtee-Pereira AG, Guo Y, Trenary I, Hernandez A, Fults JB, Williams DL, Sherwood ER, Bohannon JK.
J Immunol. 2018 Apr 23. pii: ji1800085. doi: 10.4049/jimmunol.1800085. [Epub ahead of print]
Hospital-acquired infections, particularly those caused by antibiotic-resistant pathogens, are one of the most pressing threats facing modern health care facilities. In this publication, I demonstrate that the TLR4 agonist monophosphoryl lipid A (MPLA) protects mice against infection with diverse pathogens, if given prophylactically. I further show that this protection occurs because MPLA persistently reprograms macrophage metabolism over a period of days, which fuels improved macrophage antimicrobial functions. Overall, this study advances MPLA toward clinical use as a prophylactic for patients at high-risk of infection, and demonstrates that macrophages can sustain a dynamic and functional metabolic program for much longer than previously appreciated. (By Ben Fensterheim, M3)
Co-authorships, Clinical Studies, and Reviews:
Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms.
Alexandre J, Moslehi J, Bersell KR, Funck-Brentano C, Roden DM, Salem JE.
Pharmacol Ther. 2018 Apr 23. pii: S0163-7258(18)30072-X. doi: 10.1016/j.pharmthera.2018.04.009. [Epub ahead of print] Review.
How Should Trainee Autonomy and Oversight Be Managed in the Setting of Overlapping Surgery?
Gallant JN, Langerman A.
AMA J Ethics. 2018 Apr 1;20(4):342-348. doi: 10.1001/journalofethics.2018.20.4.ecas3-1804.
Nasal saline irrigation in pediatric rhinosinusitis: A systematic review.
Gallant JN, Basem JI, Turner JH, Shannon CN, Virgin FW.
Int J Pediatr Otorhinolaryngol. 2018 May;108:155-162. doi: 10.1016/j.ijporl.2018.03.001. Epub 2018 Mar 6. Review.
Antibiotic Allergy in Pediatrics.
Norton AE, Konvinse K, Phillips EJ, Broyles AD.
Pediatrics. 2018 Apr 26. pii: e20172497. doi: 10.1542/peds.2017-2497. [Epub ahead of print] Review.
Precision Medicine with Imprecise Therapy: Computational Modeling for Chemotherapy in Breast Cancer.
McKenna MT, Weis JA, Brock A, Quaranta V, Yankeelov TE.
Transl Oncol. 2018 Apr 16;11(3):732-742. doi: 10.1016/j.tranon.2018.03.009. [Epub ahead of print] Review.
Cerebrospinal fluid β-amyloid42 and neurofilament light relate to white matter hyperintensities.
Osborn KE, Liu D, Samuels LR, Moore EE, Cambronero FE, Acosta LMY, Bell SP, Babicz MA, Gordon EA, Pechman KR, Davis LT, Gifford KA, Hohman TJ, Blennow K, Zetterberg H, Jefferson AL.
Neurobiol Aging. 2018 Apr 3;68:18-25. doi: 10.1016/j.neurobiolaging.2018.03.028. [Epub ahead of print]
Circulating Troponin I Level in Patients with Acute Ischemic Stroke.
VanHouten J, Fricker G, Collins B, Bhatia R, Ellis C, Schrag M.
Curr Neurol Neurosci Rep. 2018 Apr 20;18(6):32. doi: 10.1007/s11910-018-0842-6. Review.
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