Arvin Halim

2024 Pre-Doctoral Fellowship

Institution: Indiana University School of Medicine

Project Title: Modulating the Focal Adhesion Pathway with KL1 to Inhibit Cardiac Fibrosis in CKD

How would you sum up your overall research focus in one sentence?

My overall research focus is investigating the cardioprotective role and mechanisms of the α-Klotho protein in patients with CKD.

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

Recent studies have shown that the KL1 domain of α-Klotho, which lacks the moiety to bind to FGF23, could exert anti-fibrotic effects on the kidney and lungs through multiple fibrosis-related pathways. These pathways are known to alter focal adhesions via focal adhesion kinase (FAK) activity, which is central to fibroblast to pro-fibrotic myofibroblast transformation, yet there are no studies directly investigating if KL1 can directly regulate FAK. Our preliminary data has shown that KL1 can reduce cardiac fibrosis in a CKD rat model. Therefore, my research will investigate the hypothesis that KL1's anti-fibrotic effects involve the focal adhesion pathway by performing dose-dependent studies, spatial transcriptomics, and cellular fluorescence imaging.

What inspired you to focus your research in this area?

I was inspired by my mentor, Dr. Kenneth Lim, who was the first person to introduce me to α-Klotho and to the discipline of nephrocardiology. Over the years of participating in ASN Kidney Week, Kidney STARS and TREKS, and undergoing my PhD training, I developed a better understanding of the complications, like cardiac fibrosis, that patients with kidney disease must face with limited, if any, therapeutic options. This unmet need further solidified my commitment to continue to pursue my research on α-Klotho and its role in cardiovascular disease in CKD for my doctoral dissertation.

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

I hope my research will provide insight that will help drive the development of novel therapeutics with direct cardioprotective effects for patients burdened with kidney disease. In this way, I hope to help make a meaningful contribution to solving the problem of premature cardiovascular morbidity and mortality in patients with CKD and ESKD.

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

At the end of this grant period, I plan to finish my PhD program and apply to medical school. Five years out, I plan to complete the MD program and matriculate onto the Physician-Scientist Research Pathway toward my goal of becoming an Academic Nephrologist. By ten years, I hope to have the opportunity to apply for an NIH career development award to help develop my own research program.

What are the major challenges to beginning a career in kidney research today?

A major challenge beginning a career in kidney research is the uncertainty in obtaining funding for kidney research, particularly in the path toward becoming an independent investigator. Initiatives that the ASN is taking to help support young investigators is therefore paramount to support the pipeline of new investigators electing to pursue a career in kidney research.

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

I would recommend building up grantsmanship early in PhD training and to take up every opportunity to get involved in grant writing and scientific articles. Through these opportunities, I learned how to receive constructive feedback and to contribute to mentoring junior peers on scientific writing, which helped reinforce my writing skills as well. My experience with small grants and writing an NIH F31 proposal has made the KidneyCure grant writing process easier.

Something you may not know about me is…

I have learned how to play the pipe organ, how to break dance, and I have studied abroad in Nagoya, Japan.

In my free time I like to…

Play multiplayer online team games, care for my pet fish/cats, manage my hydroponics, discover new music, practice photography, and (if friends are available) play basketball.