Juan Fuxman Bass

Current Research

Our lab studies the mechanisms controlling gene expression in health and disease using a combination of high-throughput assays, bioinformatics, and molecular and functional studies. Transcriptional regulation plays a fundamental role in development, homeostasis, and the response to environmental cues such as pathogen infections. Indeed, gene dysregulation has been associated with multiple diseases such as immune disorders, developmental malformations, and cancer. Our long-term goal is to answer central questions in gene regulation such as: through which mechanisms are immune genes regulated during inflammatory processes? How can we modulate gene expression to treat different pathologies? Through which mechanisms do genetic variants, isoforms, and fusions affect gene expression in cancer and other diseases? How do viruses perturb and leverage host transcriptional programs?

Current projects in the lab include: 1) Viral transcriptional regulators: Virus encode for transcriptional regulators that affect the expression of viral and host genes. Our goal is to characterize the functions of these regulators, determine their roles in disease, and identify small molecules or peptides that can inhibit their function. 2) Viral cis-regulatory elements: viruses sense the cellular environment to regulate sets of genes necessary for replication. One major viral sensing mechanism involves the recruitment of host transcription factors that act downstream of different cellular signaling pathways to cis-regulatory elements in the viral genome. Our lab aims to identify the full repertoire of viral elements, their mechanisms of regulation, and their variation across isolates with the ultimate goal of identifying organismal and environmental conditions that can reactivate latent viruses and to design therapeutics to treat viral infections. 3) Effect of genetic variation on gene regulatory networks: Genetic variants in non-coding sequences as well as amino acid sequence variants, isoforms and fusions in transcription factors can have major effects on gene expression and disease. Our goal is to determine the molecular mechanisms by which these variants perturb host networks in the context of cancer and genetic disorders.

Selected Publications

• Berenson A., R. Lane, L.F. Soto, M. Patel, C. Ciausu, Z. Li, Y. Chen, S. Shah, C.S. Santoso, X. Liu, K. Spirohn, T. Hao, D.E. Hill, M. Vidal, and J.I. Fuxman Bass (2023). Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors. Nature Communications 14:6570.
• Carrasco Pro S, H. Hook, D. Bray, D. Moyer, M. Yin, A. Labadorf, R. Tewhey, T. Siggers, and J.I. Fuxman Bass (2023). Widespread perturbation of ETS factor binding sites in cancer. Nature Communications 14:913.
• Soto L., Z. Li, C.S. Santoso, A. Berenson, I. Ho, V.X. Shen, S. Yuan, and J.I. Fuxman Bass (2022). Compendium of human transcription factor effector domains. Molecular Cell 82:514-526.
• Pedro K.D., L.M. Agosto, J.A. Sewell, K.A. Eberenz, X. He, J.I. Fuxman Bass, and A.J (2021). Henderson. An unbiased functional screen identifies transcriptional networks that regulate HIV-1 and HIV-2. Proc Natl Acad Sci USA 118:e2012835118.
• Santoso C.S., Z. Li, S. Lal, S. Yuan, K.A. Gan, L.M. Agosto, X. Liu, S. Carrasco Pro, J.A. Sewell, A. Henderson, M.K. Atianand, and J.I. Fuxman Bass (2020). Comprehensive mapping of the human cytokine gene regulatory network. Nucleic Acids Research 48:12055-12073.
• Liu X., T. Hong, S. Parameswaran, K. Ernst, I. Marazzi, M.T. Weirauch, and J.I. Fuxman Bass (2020). Human Virus Transcriptional Regulators. Cell 182:24-37.
• Shrestha S., J.A. Sewell, C.S. Santoso, E. Forchielli, S. Carrasco Pro, M. Martinez, and J.I. Fuxman Bass (2019). Discovering human transcription factor physical interactions with genetic variants, novel DNA motifs, and repetitive elements using enhanced yeast one-hybrid assays. Genome Research 1533-1544.
• Fuxman Bass J.I., N. Sahni, S. Shrestha, A. Garcia-Gonzalez, A. Mori, N. Bhat, S. Yi, D.E. Hill, M. Vidal,  and A.J. Walhout (2015). Human Gene-Centered Transcription Factor Networks for Enhancers and Disease Variants. Cell 161:661-673.