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SHIP1 deficiency in IBD
Sandra Fernandes1, James C. Ryan2, William G. Kerr1
1SUNY-Upstate Medical University, Syracuse, NY2UCSF/SFVA, San Francisco, CA
Friday, December 13, 2013
DISCLOSURES
• Nothing to disclose
SHIP1 and PI3K/Akt pathway
Fernandes & al., 2013
SHIP-/- mice
Germline SHIP1-deficiency cause fatal eosinophilic pneumonia and Crohn’s-like ileitis in mice
For more on SHIP1 and mucosal inflammation in mouse model, please visit poster P-188
Kerr & al., GUT, 2011
Study Design25ml Blood
CD and UC
patients
PBMC
Protein Expression
(WB)
SHIP1
(2 Abs.)Actin,
Tubulin
miRNA
miSEQ
Total RNA
qRT-PCR
SHIP1 (2 sets
primers)
RPLP1, PPIA
DNA
Sequencing exome
30 x700bp amplicons
Western Blotting
SHIP1 : P1C1 + goat anti-mouse HRP, Actin : C-19 + donkey anti-goat HRP, Santa Cruz Biotechnologies
Reproducibility, Stability
Protein levels vs mRNA
Protein levels vs mRNA
Protein degradation or translation inhibition?
Modified from Grabbe & al. 2011 Ameres & Zamore, 2013
Take home message
• SHIP1-deficiency is found in 10/47 samples (>20% of samples)
• Both CD and UC• SHIP1-deficiency is stable over months• No correlation to treatments at time of
sampling or to other clinical parameters• No reduction in SHIP1 mRNA levels
– Translational or post-translational
Acknowledgments• William Kerr• James Ryan and his team at
UCSF/SFVA
• Neetu Srivastava• Raki Sudan• Bonnie Toms
• Robert Brooks• Matt Gumbleton• Sonia Iyer• Sudha Neelam• Christie Youngs
• Katie Miller• Scott Stegemann• Summer students
• CCFA (Senior Research Award to WGK)
• NIH• Paige Arnold Butterfly Run• Carol M. Baldwin Foundation
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