Function and significance of post-translational modification by SUMO in the heartÂ
Proper protein quality control is required to maintain normal cardiac function. The Ubiquitin Proteasome System (UPS) and autophagy play an important role in the maintenance of cellular proteostasis. Our study found that SUMO E2 ligase UBC9 regulates cardiomyocytes’ cellular protein quality control. The novelty and significance of this project is that SUMOylation is tightly controlled in the cardiomyocytes and is compromised during the development of cardiac pathology induced by increased proteotoxic load. We significantly reduced the proteotoxic load and increased cellular viability by modulating SUMOylation activity in cardiomyocytes using gain- and loss-of-function approaches. To learn more about our SUMOylation work, click here and here
Role of molecular chaperone in protein homeostasis and aggregate disease
Molecular chaperones significantly regulate cellular function through protein folding, translocation, and degradation using cellular protein quality control. Expression of chaperones upregulated in cellular stress like oxidative stress, heat shock etc. The Bcl2-associated anthanogene (BAG) family is a set (BAG1-BAG6) of multifunctional co-chaperone proteins that plays an important role in the cell and protects cells from stress-induced cell death. Our lab is studying the role of BAG5 protein in cellular function using mice models of heart failure. To learn more about our BAG5-related work, click here and here.
Regulation of mitochondrial function and cellular bioenergetics during health and disease
Small molecule and epigenetic-based therapy for metabolic diseases
Epigenetics plays an important role in the regulation of gene expression at the transcriptional level. Aberrant epigenetic changes lead to the growth defect and development of cardiovascular disease. Post-translation modification (PTM), like DNA methylation and acetylation, can impact the regulate the physical properties of chromosome and their transcription. Acetylation is the histone’s first known PTM that regulates chromatin’s open and close configuration. Our study found that the level of acetylation significantly changed during cellular stress like hypoxia, drug toxicity, and infection. Further, we want to investigate the role of epigenetic enzymes in the regulation of histone acetylation at the basal level and during disease conditions. Additionally, we are interested in finding small drug molecules that can regulate the acetylating enzyme function and acetylation of histone. To learn more about our epigenetic research, click here.
Understanding the role of HIV-1 and antiretroviral drugs in the development of cardiomyopathy
Human Immunodeficiency Virus (HIV) was discovered 40 years ago, and we are still looking for a cure to eliminate it from patients. Antiretroviral therapy controls the viral load and prevents AIDS-like symptoms in patients. However, drug treatment does not remove the virus entirely from the patients. HIV becomes a chronic disease, and people living with HIV experience a higher risk of non-AIDS-related comorbidities, including metabolic disease. Cardiovascular disease remains one of the leading causes of death in PLWH.Additionally, viral infection increases the inflammation and probability of co-infection with opportunistic pathogens. Moreover, published literature suggests that Antiretroviral therapy has a toxic effect and compromises organ function. Our data show that combined antiretroviral drug therapy induces cardiotoxicity and reduces cellular viability. To learn more about our HIV and ART-related research, click here and here.