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Transcript of Omenn Syndrome and RAG1 Nicholas Moehn Photo from:
![Page 1: Omenn Syndrome and RAG1 Nicholas Moehn Photo from:](https://reader036.fdocuments.us/reader036/viewer/2022070401/56649f185503460f94c2edbd/html5/thumbnails/1.jpg)
Omenn Syndrome and RAG1
Nicholas Moehn
Photo from: http://beyondessential.com/healthy-immune-system/
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What is Omenn Syndrome?
http://showyourhope.com/2012/11/04/http://en.wikipedia.org/wiki/Omenn_syndrome#mediaviewer/File:Omenn_syndrome.png
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What causes Omenn Syndrome?
RAG1
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How does RAG1 work?
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How well is RAG1 conserved?
99%
76%
59%
75%
90%
AA
AA
AA
AA
AA
AA
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Where is RAG1 mutated in OS?
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What organisms contain RAG1?
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A possible second player?
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What causes Omenn Syndrome?• Goal: To explore how AIRE and RAG1 contribute to
the Omenn syndrome phenotype
• Hypothesis: Mutations in RAG1, in combination with deficiency in AIRE, creates the small, oligoclonal population of self-reactive immune cells present in individuals with Omenn syndrome.
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Aim 1: Determine if all individuals with Omenn syndrome are deficient for AIRE
RAG1
AIREImmunodeficiency
SCID
AIRE RAG1Omenn Syndrome????
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Approach: RNAseq
http://fcsanahuac.com/category/temas-selectos-de-ciencias-de-la-salud/
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Aim 2: Identify mutations that would cause autoimmune symptoms
RAG1
AIRE
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Approach: Next Gen Sequencing
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Aim 3: Demonstrate that deficiency in RAG1 and AIRE is sufficient to cause OS
RAG1
AIRE Immunodeficiency
SCID
AIRE RAG1 Omenn Syndrome?
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Approach: Crispr-Cas9 to create mutants
Crispr-Cas9
http://de.wikipedia.org/wiki/Durchflusszytometrie
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Approach: Quantitative proteomics and cell counting
Cell counts
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Future Directions
• Take advantage of the knowledge of AIRE mutation to try to develop a new treatment for patients with Omenn syndrome
• To apply knowledge of Omenn syndrome to other SCIDs, immunodeficiencies, and autoimmune disease