Ruben Barricarte, PhD, MSc

Ruben Martinez-Barricarte's work lies at the crossroads of human genetics, biochemistry, immunology, and infectious diseases. For the past decade, he has worked on the genetic study of monogenic human immune diseases. His graduate studies involved the genetic dissection of two very severe kidney diseases: atypical hemolytic uremic syndrome (aHUS) and dense deposit disease (DDD). By discovering and functionally characterizing mutations in the C3 gene in patients suffering from aHUS and DDD, he established how dysregulations in the complement system cause these two disorders, thus providing useful information for their treatment. His postdoctoral studies focused on the genetic dissection of Mendelian susceptibility to mycobacterial disease (MSMD). Patients suffering from this condition develop severe disease when exposed to weakly virulent mycobacteria such as environmental mycobacteria. By next-generation sequencing MSMD patients, and in collaboration with other colleagues, he discovered human SPPL2a, IL-12RB2, and IL-23R complete deficiencies. The in-depth molecular and immunological characterization of these new genetic diseases provided fundamental knowledge of how the immune system fights mycobacteria. In addition, he has also discovered and functionally characterized disease-causing mutations in other diseases such as CFHR5 nephropathy, chronic granulomatous disease, and combined immunodeficiency. Using his skills in the genetic and immunological dissection of monogenic inborn errors of immunity, his lab investigates nocardiosis and blastomycosis. Though exposure to Nocardia spp. and Blastomyces dermatitidis is common, only a small fraction of individuals develop severe disease. Therefore, his research program focuses on understanding the genetic and immunological factors that account for this interindividual variability.