Voelcker Academy

Research Symposium 2011

 

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Anand Ahuja

Using Whole Genome Transcriptional Profiling to Identify Novel Therapeutic Targets for Allergic Rhinoconjunctivitis

Anand Ahuja

Mentor(s): Sunil K. Ahuja, MD

Introduction: Allergic rhinoconjunctivitis (AR) affects millions of people worldwide, yet there is still a gap in the knowledge of the genetic hallmarks of allergic responses and a lack of specific therapeutic targets for mediating allergic response.

Methods: RNA-Seq and protein expression level data taken from subjects before and after exposure to Juniperus ashei pollen (Mountain Ceder pollen) in an environmentally controlled chamber were used to explore genes, proteins and pathways involved in allergic rhinoconjunctivitis. The statistical analysis program R was used to investigate differential expression of genes and proteins between subjects that did and did not mount an allergic response, while the programs IPA (to identify biological pathways associated with the differential gene expression) and Pajek (to create novel associations in the data using creative algorithms) were used for additional analyses.

Results: The comparison between post-challenge individuals showed 951 genes significantly associated with whether or not a subject mounted an allergic response; the comparison between positive-responding individuals, before and after challenge with the allergen, showed 252 genes significantly associated with mounting an allergic response. These genes were most notably associated with the canonical pathways that demonstrated the subjects’ bodies responding to the allergen by increasing energy production, possibly placing excessive stress on the individuals to produce that energy (related to mitochondrial dysfunction). It was also observed that the cytokines Eotaxin, MDC and TRAIL were significantly correlated with the severity of symptoms recorded during allergic response.

Conclusions: AR was demonstrated to be characterized by a multitude of genes rather than a single 'smoking gun.' However, many genes implicated in allergic response have a previously demonstrated involvement with high levels of energy production. Potential targets that could lead to the development of novel therapeutic treatments for allergy sufferers could include the overarching genetic expression patterns during the allergic response, the pathways involved in this energy production, as well as the cytokines Eotaxin, MDC, and TRAIL.

Collaborators: Sunil Ahuja, M.D, Nathan Harper, B.S.