Ana Fiszbein

Current Research

Our lab uses a combination of high-throughput, functional genomics, bioinformatics and molecular approaches to study the co-transcriptional gene regulation of mammalian expression programs.
The architecture of mammalian genes enables the production of multiple transcripts by using alternative promoters, alternative termination sites, and differentially spliced exons, which greatly expand the coding capacity of our genomes. Understanding how alternative RNA-processing events influence gene expression is of particular importance in cancer genomics, as their aberrant regulation contributes to the ~10 million cancer-related deaths each year.
Several effects of transcription on splicing have been established, and functional feedback from splicing to transcription has started to emerge. We recently characterized the phenomenon of Exon-Mediated Activation of Transcription Starts (EMATS), in which the splicing of internal exons impacts the spectrum of promoters used and expression levels of the host gene. However, a global understanding of the impacts of gene architecture and RNA-processing events in gene regulation is lacking, and the consequence in cells remains to be elucidated.

Our goal is to understand how gene architecture orchestrates the dynamic regulation of gene expression in normal cells and disease. We aim to build new computational tools to predict gene regulatory programs from genome sequences and gene architecture and design new strategies to manipulate gene expression with therapeutical purposes. We currently seek to understand three key aspects of gene regulation: (i) how promoter sequences drive RNA processing decisions, (ii) how transcription interferes with expression from nearby promoters, and (iii) how transcript starts and transcript ends are connected.

We are recruiting undergrads, grad students and postdocs. Get in touch!

Selected Publications

• Uriostegui-Arcos M, Mick ST, Shi Z, Rahman R, and Fiszbein A (2023). Splicing activates transcription from weak promoters upstream of alternative exons. Nature Communications 14:3435.
• Fiszbein A, McGurk M, Calvo-Roitberg E, Kim GY, Burge CB, and Pai, AA (2022). Widespread occurrence of hybrid internal-terminal exons in human transcriptomes. Science Advances 8:eabk1752.
• Fiszbein A, Krick KS, Begg BE, and Burge CB (2019). Exon-mediated activation of transcription starts. Cell 79:1551-1565.
• Fiszbein A and Kornblihtt AR (2017). Alternative splicing switches: Important players in cell differentiation. BioEssays 39:1600157.
• Fiszbein A and Kornblihtt AR (2016). Histone methylation, alternative splicing and neuronal differentiation. Neurogenesis 3:2326-2133.
• Fiszbein A, Giono LE, Quaglino A, Berardino BG, Singaut L, von Bildering C, Schor IE, Steinberg JHE, Rossi M, Pietrasanta LI, Caramelo JJ, Srebrow A, and Kornblihtt AR (2016). Alternative splicing of G9a regulates neuronal differentiation. Cell Reports 14:2797–2808. Featured on the cover.
• Schor IE, Fiszbein A, Petrillo E, and Kornblihtt AR (2013). Intragenic epigenetic changes modulate NCAM alternative splicing upon neuronal differentiation. EMBO Journal 32:2264-74.
• Fiszbein A, Cánepa M, Vázquez GR, Maggese C, and Pandolfi M (2010) Photoperiodic modulation of reproductive physiology and behavior in the cichlid fish Cichlasoma dimerus. Physiology and Behaviour 99:425-32.