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Damage Associated Molecular Patterns

 

 

Our laboratory has quantified mtDNA in red cell units manufactured using several different processing methods.  We showed that manufacturing processes significantly influence the levels of mtDNA, a so-called damage-associated molecular pattern that may have immunomodulatory effects.  We also measured mtDNA in platelet concentrates and found increased levels upon pathogen inactivation during storage. 

In a second area of study, we developed PCR assays that can quantify nucleic acid modifications induced by pathogen reduction technologies.  These technologies generally rely on photochemical treatment to reduce the infectious risk in blood components.  Our assays could provide a valuable tool for blood centers to monitor the efficacy of pathogen reduction.

 

Selected Publications:

 

Lauring AS, Lee TH, Martin JN, Hunt PW, Deeks SG, Busch MP. Lack of evidence for mtDNA as a biomarker of innate immune activation in HIV infection. PLoS One 7(11):e50486 PMC3510194 (2012).

Bakkour S, Chafets DM, Wen L, van der Meer PF, Mundt JM, Marschner S, Goodrich RP, Busch MP, Lee TH. Development of a mitochondrial DNA real-time polymerase chain reaction assay for quality control of pathogen reduction with riboflavin and ultraviolet light. Vox Sang 107(4):351-9 (2014).

Bakkour S, Chafets DM, Wen L, Dupuis K, Castro G, Green JM, Stassinopoulos A, Busch MP, Lee TH. Assessment of nucleic acid modification induced by amotosalen and ultraviolet A light treatment of platelets and plasma using real-time polymerase chain reaction amplification of variable length fragments of mitochondrial DNA. Transfusion 56(2):410-20 (2016).

Bakkour S, Acker JP, Chafets DM, Inglis HC, Norris PJ, Lee TH, Busch MP. Manufacturing method affects mitochondrial DNA release and extracellular vesicle composition in stored red blood cells. Vox Sang 111(1):22-32 (2016).

Chen Z, Schubert P, Bakkour S, Culibrk B, Busch MP, Devine DV. p38 mitogen-activated protein kinase regulates mitochondrial function and microvesicle release in riboflavin- and ultraviolet light-treated apheresis platelet concentrates. Transfusion doi:10.1111/trf.14035 (2017).