Carlos Javier Orihuel, Ph.D.

Since graduate school, my research focus has been Streptococcus pneumoniae (Spn) disease progression: asymptomatic nasopharyngeal colonization → pneumonia → invasive disease. In obtaining a molecular understanding of this bacterium’s pathogenesis, I hope to discover basic tenets of biology and identify new strategies for disease prevention or treatment. As a postdoc, I identified 37/67 Laminin Receptor as the ligand Spn and other neurotropic pathogens co-opt to cross the blood-brain barrier to cause meningitis. As a junior faculty member, I worked to characterize the role of pneumococcal serine-rich repeat protein (PsrP) as a determinant for pneumonia in older adults. Today, my research endeavor is focused on myocardial invasion, the anatomical-site specific transcriptome of Spn in vivo, and the role of the pore-forming toxin pneumolysin in the induction of host cell necroptosis. Across all aspects of my research program, I strive to incorporate the most precise and powerful molecular tools and procedures. Today my laboratory is using isogenic marker-free Spn mutants and their genetically complemented controls, CRISPR-Cas9 gene-edited host cell lines, custom made transgenic mice, and dual-species RNAseq for examination of host and bacterial gene expression in vivo. We regularly use Ingenuity Pathway Analysis and other bioinformatic analytical tools to uncover the biological significance in our ‘omics data. Over the course of my career, I have become proficient in the genetic manipulation of Spn and eukaryotic cells, protein expression and purification, flow cytometry, immunofluorescent and electron microscopy, and the use of a wide range of animal models pertaining to Spn disease. These tools and skills are an integral part of the research that goes on in my lab today.