Karthi Sreedevi
Faculty Mentor
Junco Warren
Assistant Professor
Research Areas/Interests
Cardiovascular sciences, glycosylation, glycobiology, heart failure, neurodegeneration, anti-carbohydrate antibodies
How long have you been in your postdoctoral position at Virginia Tech?
Began in December 2021
Briefly describe the research project you are working on as a postdoctoral associate at Virginia Tech. What is the problem you are addressing? What is the expected impact of your work?
Heart failure is a leading cause of death worldwide. Despite significant advances in medical treatments, 50% of patients still die within 5 years of diagnosis. Thus, developing new strategies to treate heart failure patients is urgently needed. Our group recently demonstrated that novel muscle-specific regulator Perm1 (PGC-1 and ERR regulator in muscle 1) is downregulated in human and mouse failing hearts, suggesting the role of Perm1 in the pathogenesis of heart failure. However, it remains unclear how Perm1 regulates cardiac function in health and diseased hearts.
My long-term goal is to develop novel therapeutic strategies to treat heart failure patients. I hypothesize that Perm1 is cardioprotective and suppresses excessive O-GlcNAcylation of proteins under pathological stress. O-GlcNAcylation is a post-translational modification and in response to stress, it regulates protein function, location, and turnover. Recent studies have demonstrated that pressure overload in the heart results in the increase of O-GlcNAcylation and that excessive O-GlcNAcylation of proteins leads to teh development of heart failure. My preliminary results show that Perm1-knockout mice exhibit reduced cardiac function in association with the increased levels of O-GlcNAcylation of proteins in the heart. Furthermore, I showed that Perm1 overexpression in cultured cardiomyocytes led to downregulation of O-GlcNAc tranferase (OGT), a key enzyme that increases O-GlcNAcylation. In this project, I will determine 1) whether Perm1 is a transciptional repressor of OGT and 2) whether Perm1 overexpression via adenovirus-meidated gene delievery in mice can protect against cardiac dysfunction during pressure overload through suppressing excessive O-GlcNAcylation.
This study will uncover a novel role of Perm1 as an essential regulator of cardiac functin and O-GlcNAcylation in the heart. This study may also lead to the development of a new therapeutic strategy to treat heart failure.
Why did you choose to pursue postdoctoral training at Virginia Tech?
Virginia Tech is one of the top-ranked universities in the world and the Fralin Biomedical Research Institute at Virginia Tech Carilion is one of the fastest-growing research institutes in the US. The research environment available is excellent and that gives me immense confidence that I will be able to succeed in my career by working at Virginia Tech.
What are your career goals?
My career goal is to be an internationally known principal investigator in the field of cardiac glycobiology and translate my research findings to clinical care to improve the lives of patients suffering from cardiovascular diseases.
How do you see the resources available to postdoctoral associates at Virginia Tech generally and via this program specifically being helpful to your career and professional development?
Virginia Tech supports postdoctoral associates to develop professionally by providing fellowships, scholarships, and travel grants. The Virginia Tech Postdoctoral Association organizes meetings and community hangouts where peers can interact. I hope this program will help me in networking with researchers and scientists within and outside my field and provide support in developing professional skills like public speaking, grant writing, and leadership.