Diversity Initiatives Endowment Award Recipient Attends Bioinformatics Workshop

By Giovan Cholico posted 12-13-2018 15:32


As a recipient of the SOT Diversity Initiatives Endowment Career Development Award, I was given an amazing opportunity to study differential gene expression methods at the National Center for Genome Research (NCGR) in Santa Fe, New Mexico. During this week-long workshop at NCGR, I became proficient in using a wide variety of bioinformatic tools to analyze my own RAW RNA-seq results. I learned the ins-and-outs of how to build a reliable (and personalized) bioinformatics pipeline by using command line applications like HISAT2 and HTSeq as well as R applications like DEseq2. I also learned how to conduct gene ontology and pathway analyses using data from a differential gene expression analysis. It is my hope that bioinformatic methods I learned in this workshop will help me finish up my graduate degree before embarking on a career in bioinformatics. In the photo below, I am in the server facility at NCGR.

NCGRServerPicture1.jpgThere is accumulating evidence that implicates the aryl hydrocarbon receptor (AhR) in mediating liver fibrosis. My doctoral project investigates the role of the AhR in hepatic stellate cells (HSC) for mediation of liver fibrosis. Upon liver injury, it is these HSCs that become activated and begin remodeling the extracellular matrix (such as depositing collagen) to promote a fibrotic pathology. In my experiments, we use a murine model system that has been treated with CCl4 to induce an initial level on liver damage and promote fibrosis. We then use TCDD to activate the AhR and see how the liver pathology changes. In our experiments, we use two lines of mice that possess either hepatocyte- or HSC-specific knockout of the AhR to explore how this receptor can affect the end-state pathology of the liver. I am interested in learning if HSCs are directly activated by TCDD (through the AhR), or if activation of the TCDD-treated HSCs occurs indirectly through parenchymal necrosis or maybe even inflammation.

One of my projects involves using RNA-sequencing to look at which pathways were dysregulated in the mouse livers that led to HSC activation, and therefore a more pronounced fibrosis pathology in the liver. Using the bioinformatic tools I learned at NCGR, I will evaluate the myriad of dysregulated gene sets that led to more pronounced HSC activation levels in my model system. Some of the pathways that I have begun to evaluate include: hepatocyte damage responses, inflammatory responses, HSC activation pathways, fibrogenesis pathways, ECM remodeling gene sets, and glycogen metabolism. Overall, my experience at NCGR, studying under the guidance of bioinformaticians was immensely worthwhile. I look forward to continuing to hone my informatic techniques and hope to publish data from this trip soon. 


Fellow workshop attendees mingling over lunch

The SOT Diversity Initiatives Endowment Career Development Award enables undergraduate and graduate students to engage in additional education and career development opportunities to enhance their personal development. Administered by the Committee on Diversity Initiatives, the SOT Diversity Initiative Endowment Fund provides the award that aims to increase and retain individuals from groups under-represented in the biomedical sciences. Recipients of this award are chosen based on criteria that include quality of proposed experience, relevance of the proposed professional activity to a career involving the science of toxicology, academic achievement, and recommendation by academic advisor. The next deadline for applications is April 10, 2019.