Juan Fuxman Bass

Our lab studies the mechanisms controlling the expression of immune genes. Transcriptional regulation plays a fundamental role in proper immune development and homeostasis as well as in mounting immune responses against pathogens. Indeed, mutations in the regulatory regions of immune genes such as cytokines, receptors and signaling molecules have been associated with multiple pathologies including autoimmune diseases, cancer and susceptibility to infections. After decades of research, however, many aspects of immune transcriptional regulation are still not well understood, as most studies have focused on only a few dozen of the ~1,500 human transcription factors (TFs) leaving a large portion of the gene regulatory network unexplored. This bias towards a limited number of TFs is both historical and methodological, as TFs with available reagents are more highly studied and current methods such as chromatin immunoprecipitation (ChIP) test one TF at a time.

We have recently developed an enhanced yeast one-hybrid (eY1H) platform that can interrogate for the binding of 1,086 human TFs (out of ~1,500) to different regulatory regions. Our main goal is to delineate an unbiased immune gene regulatory network by comprehensively identifying the TFs that bind to the regulatory regions of different immune genes and to determine which TF-DNA interactions are affected by disease-associated mutations in non-coding regions. To achieve this goal we use an interdisciplinary approach that merges high-throughput screening of TF-DNA interactions using eY1H assays, functional genomics, bioinformatics and cell biology. Our long-term goal is to answer central questions in immune regulation such as: through which mechanisms are immune genes regulated during inflammatory processes? How can we modulate the regulatory network in immune cells to more effectively respond to infectious diseases and pathological conditions? How do non-coding mutations impact immune gene expression leading to disease?

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