Nastaran Daneshgar successfully defended her doctoral thesis in early June and graduated from the Experimental Pathology Ph.D. Program. Her thesis, Klotho-Sirt1-CHK2 Pathways in the Regulation of Cardiac Function in Aging and Post-Myocardial Injury, focuses on aging and cardiac function, offering promising insights into potential therapeutic interventions for age-related cardiac diseases. She conducted her thesis work in the laboratories of Dr. Dao-Fu Dai and Dr. Chad Grueter, utilizing a combination of human tissue, mouse models, and human-derived stem cell models.
Aging significantly impacts cardiac function, predisposing the elderly population to heart failure. Nastaran investigated the therapeutic potential of the anti-aging hormone α-Klotho (sKL) in mitigating these age-related phenotypes through modulation of the Sirtuin1 (Sirt1)-Checkpoint kinase 2 (CHK2) signaling pathway. Key findings from the study include the reversal of aging-related changes, enhanced proliferative markers, and reduced DNA damage in the heart. Additionally, sKL supplementation improved cardiac function by mitigating cardiac hypertrophy, diastolic dysfunction, and exercise intolerance, suggesting a promising intervention for heart failure.
The study also examined the role of CHK2 in cardiomyocyte proliferation during development and post-myocardial infarction (MI). CHK2 suppression post-MI improved cardiac function, reduced scar size, and increased markers of cardiomyocyte proliferation. Spatial transcriptomic analysis revealed that hearts with suppressed CHK2 maintained a healthier cardiomyocyte population with upregulation of genes promoting mitochondrial biogenesis and enhanced cardiac contractility, indicating a shift towards an active state favorable for repair and adaptation. In addition to Dr. Dai and Dr. Grueter, Drs. Bing Li, Jia Luo, and Long-Sheng Song served on her thesis committee.
Notably, aside from publishing her dissertation, Nastaran has published ten papers during her graduate studies, showcasing her extensive research contributions to the field. In seven of these publications, she was the lead author and contributed to all aspects of the research.