Name: Sian Piret, PhD

Institution: Stony Brook University

Grant: 2020 Joseph V. Bonventre Research Scholar Grant

Project Title: Transcriptional Regulation of Proximal Tubular Amino Acid Metabolism in AKI

How would you sum up your research in one sentence?

• My research is aimed at understanding the roles of proximal tubular transcription factors, particularly members of the Krüppel-like factor (KLF) family, and how their actions determine cellular outcomes during and after AKI.

Provide a brief overview of the research you will conduct with help from the grant.

• We have previously shown that loss of KLF6 in the proximal tubule is protective during AKI, and that this is associated with preservation of genes encoding branched chain amino acid (BCAA) catabolic genes. We now aim to determine whether manipulations of BCAA catabolism affect the severity of AKI, and the mechanisms by which this occurs.

What inspired you to focus your research in this area?

• I have been interested in kidney physiology since I was in high school, and there is still so much about normal physiology, AKI, and recovery after injury that we don’t fully understand. KLF6 is upregulated in AKI resulting from multiple causes (sepsis, ischemia-reperfusion, drug-induced), making it an important protein to study. Furthermore, proximal tubule cellular metabolism is becoming increasingly understood as being critical to the progression to CKD or recovery after AKI.

What impact do you hope your research will have on patients?

• There are currently no therapeutic options to treat AKI or CKD, which represents a critical gap in caring for patients. Drugs targeting transcription factors have therapeutic potential due to their function in regulating multiple targets, with relatively small changes in activity. We hope to identify potential new therapeutic targets for development of drugs to treat AKI.

What are your career goals at the end of the grant period? Five years out? Ten years out?

• I hope this grant will enable better understanding of the role of amino acid metabolism in the proximal tubule and specifically in the setting of AKI. I hope to generate the data to move towards having an independent grant and eventually a research group that will make valuable contributions in the field of AKI and CKD.

What has surprised you most about your career?

• When I studied biochemistry as an undergraduate, I was not overly excited by metabolic pathways, and much more interested in human disease mechanisms. I didn’t think that many years later the two subjects would coincide!

In one sentence, please describe the importance of having grant funding available through KidneyCure.

• It represents my first major step towards a career as an independent researcher and allows me to explore a new research area with potential therapeutic benefit.

What advice would you give to others to encourage them to apply for this grant funding?

• The only guaranteed way to not get a grant is to not apply! Give it your best shot, and no effort is wasted since reviewers’ comments with a rejection can be as helpful as a success.

Something you may not know about me is…

• Before I moved to the US from the UK, in my non-research life I was a soccer referee, working on semi-professional and professional men’s and women’s matches.

In my free time I like to…

• Run, and play, sing and listen to classical music.