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RESEARCH INTERESTS: mechanisms of regulation of alternative splicing, antigen-induced splicing in T cells
Recent insight into the human genome has revealed that most genes encode multiple distinct protein isoforms through the process of alternative pre-mRNA splicing. My laboratory is focused on understanding the biochemical mechanisms and regulatory networks that control alternative splicing in response to antigen-challenge of the human immune system. In addition, we are working to characterize the physiological consequences of this mode of gene regulation. Recently we have identified ~150 genes that exhibit an alteration in isoform expression in response to T cell stimulation. Through our initial work on the regulated splicing of the protein tyrosine phosphatase CD45, we have identified the regulatory sequence and proteins that controls activation-induced isoform expression of CD45 as well as several other genes essential for T cell function. This work is on-going as we seek to understand the mechanism of this regulation in more molecular detail. Moreover the analysis of binding specificity of the proteins involved in signal-responsive regulation is allowing us to predict further examples of regulated splicing in the immune system. Finally, the generation of mice deficient in their expression of critical splicing regulatory proteins is allowing us to dissect the functional significance of alternative splicing for the proper function of the mammalian immune system. Together these studies are providing new insights into the mechanisms and consequences of RNA-based gene regulation in the cellular response to environmental stimuli.
Recent insight into the human genome has revealed that most genes encode multiple distinct protein isoforms through the process of alternative pre-mRNA splicing. My laboratory is focused on understanding the biochemical mechanisms and regulatory networks that control alternative splicing in response to antigen-challenge of the human immune system. In addition, we are working to characterize the physiological consequences of this mode of gene regulation. Recently we have identified ~150 genes that exhibit an alteration in isoform expression in response to T cell stimulation. Through our initial work on the regulated splicing of the protein tyrosine phosphatase CD45, we have identified the regulatory sequence and proteins that controls activation-induced isoform expression of CD45 as well as several other genes essential for T cell function. This work is on-going as we seek to understand the mechanism of this regulation in more molecular detail. Moreover the analysis of binding specificity of the proteins involved in signal-responsive regulation is allowing us to predict further examples of regulated splicing in the immune system. Finally, the generation of mice deficient in their expression of critical splicing regulatory proteins is allowing us to dissect the functional significance of alternative splicing for the proper function of the mammalian immune system. Together these studies are providing new insights into the mechanisms and consequences of RNA-based gene regulation in the cellular response to environmental stimuli.
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Scientific reportsno. 1 (2024): 10987-10987
Xiaolei Liu, Sudhish A. Devadiga,Robert F. Stanley, Ryan Morrow,Kevin Janssen,Mathieu Quesnel-Vallières,Oz Pomp,Adam A. Moverley,Chenchen Li,Nicolas Skuli,Martin P. Carroll,Jian Huang,
biorxiv(2024)
Nature Immunologyno. 11 (2023): 1933-1946
S. Gao,M. Esparza, I. Dehghan,V. Aksenova, K. Zhang,K. Batten,M. B. Ferretti,B. E. Begg T. Cagatay,J. W. Shay,A. Garcia-Sastre,E. J. Goldsmith,Z. J. Chen,
Cell reportsno. 8 (2023): 112988-112988
Rachel M. Braun,Max Ferretti, Jesse Miller, Lauren Castellana,Jae Seung Lee,Kristen W. Lynch,Sara Cherry
Journal of Immunologyno. 1 (2023): 236.08-236.08
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Xiaolei Liu, Sudhish A. Devadiga,Robert F. Stanley, Ryan Moroow,Kevin A. Janssen,Mathieu Quesnel-Vallières,Oz Pomp,Adam A. Moverley, C. Y. Li,Nicolas Skuli,Martin Carroll,Jian Huang,
bioRxiv (Cold Spring Harbor Laboratory) (2023)
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