In an era where sequencing of the human genome, and the genomes of many other species have been identified, the challenge remains: What genes are biomarkers of severe trauma and burn injury, and secondly, is there a functional role for these genes? We have focused on bioinformatic mining techniques in human leukocytes to identify and characterize orphan genes (i.e. genes with no known function) that encode ligands/peptide hormones. Here, our goal is to use such techniques to identify biomarkers and functional gene products that can be used to better understand the pathophysiology of multiple organ failure in trauma/burn patients. To this end, we have recently identified one such gene, Ecrg4, which encodes a membrane-anchored peptide, which is released upon injury, as a specific example of a gene that we de-orphanized with these techniques and has both clinical relevance and a functional role in the innate immune response.
Gonzalez AM, Podvin S, Lin S, Miller MC, Botfield H, Leadbeater WE, Roberton A, Dang X, Knowling SE, Cardenas-Galindo E, Donahue JE, Stopa EG, Johanson CE, Coimbra R, Eliceiri BP, Baird A. Ecrg4 expression and its product augurin in the choroid plexus: impact on fetal brain development, cerebrospinal fluid homeostasis and neuroprogenitor cell response to CNS injury. Fluids Barriers CNS 2011 Jan 18;8(1):6. PMCID: PMC3042980
Podvin S, Gonzalez AM, Miller MC, Dang X, Botfield H, Donahue JE, Kurabi A, Boissaud-Cooke M, Rossi R, Leadbeater WE, Johanson C, Coimbra R, Stopa EG, Eliceiri BP, Baird A. Esophageal cancer related gene-4 is a choroid plexus-derived injury response gene: evidence for a biphasic response in early and late brain injury. PLoS One 2011 6(9):e24609. PMCID: PMC3173480
Baird A, Coimbra R, Dang X, Lopez N, Lee J, Krzyzaniak M, Winfield R, Potenza B, Eliceiri BP. Cell surface localization and release of the candidate tumor suppressor Ecrg4 from polymorphonuclear cells and monocytes activate macrophages. J Leukoc Biol 2012 May;91(5):773-81. PMCID: PMC3336773
Dang X, Podvin S, Coimbra R, Eliceiri B, Baird A. Cell-specific processing and release of the hormone-like precursor and candidate tumor suppressor gene product, Ecrg4. Cell Tissue Res 2012 Jun;348(3):505-14. PMCID: PMC3367106
Shaterian A, Kao S, Chen L, di Pietro L, Coimbra R, Eliceiri BP, Baird A. The candidate tumor suppressor gene Ecrg4 as a wound terminating factor in cutaneous injury. Arch Dermatol Res 2012 Aug 17, Epub ahead of print.