Translating Research to Bedside in the Field of Hematology-Oncology

Sudhish Devadiga, COL ’24, Voorhees, NJ

This past summer, I continued my journey of investigation in the realm of hematological malignancies. I have conducted research in the Klein Lab, a translational hematology-oncology lab, since my freshman year, mentored by postdoc Xiaolei Liu. Translational research is such a fascinating branch of research to me since it bridges the gap between the lab bench and the patient’s bedside. Being able to directly contribute towards basic science discoveries that could potentially be passed on to clinicians to transform them into treatments for real patients battling blood-related diseases and cancers feels like such a privilege. 

I was able to really dig deep this summer to wrap up a particularly exciting project that I have been working on for the past 1.5 years. The work is on targeting the biological process of mitophagy in SRSF2 splicing factor mutant hematological malignancies. Mitophagy is essentially a maintenance process in cells that involves removing damaged mitochondria through a process called autophagy. In mitophagy, a surveillance factor called PINK1 signals the presence of damaged mitochondria. Moreover, splicing factor mutations like SRSF2 are extremely common in hematological malignancies. We noticed that the SRSF2 mutation results in impaired mitochondrial function and increased mitophagy. By targeting PINK1, we could exploit the SRSF2 mutant cells’ dependence on mitophagy, selectively killing them off while preserving the wild-type ones.

I specifically started this summer off by analyzing genome-wide splicing events using the rMATS pipeline, particularly in SRSF2 mutants to find potential genes responsible for the mechanism of the mutation’s effect on mitochondrial dysregulation and mitophagy. I further utilized techniques like RT-PCR to confirm these computational results through bench work. I also investigated the effect of inhibiting an enzyme known as GSK-3, a key player in splicing regulation. I confirmed several genes that had further alternative splicing changes when cells were treated with a GSK-3 inhibitor, validating that GSK-3 inhibition further reduces splicing fidelity. Towards the end of the summer, I began investigating which mitochondrial complex is responsible for the mechanism of the PINK1 alternative splicing change. I cultured my own K562 leukemia cell line, treating it with various specific mitochondrial complex inhibitors and analyzing the resulting splicing of PINK1 after 24 hours to observe any changes. I intend on progressing on this project throughout the upcoming academic year.

By working full-time this summer, I was able to second-author a manuscript as a culmination of this project. It is currently being sent out for review, in the hopes of eventual publication. I am so grateful for having received the Career Services Summer Funding Grant, without which my contribution to these projects would not have been as readily possible. And of course, I am always thankful for Dr. Peter Klein and Xiaolei Liu, who have directly guided me throughout my undergraduate career and piqued my interest in the field. I hope to continue conducting research in this field while in medical school, and I am excited about future possibilities to incorporate it further beyond into my clinical practice as a future physician.

This is part of a series of posts by recipients of the 2023 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here

By Career Services
Career Services