Page 71 - _NIPER-G Annual Report 2019-201

DEPARTMENT RESEARCH HIGHLIGHTS

Research Area 1

1. Cardiometabolic disease: Understanding disease mechanisms, target

identification and therapeutic intervention
Biotechnology Department research focus is to identify novel targets and understand
the molecular mechanisms of chronic and complex diseases like cardiac hypertrophy,
heart failure, diabetes and non-alcoholic fatty liver disease. The research revealed
several novel cellular signalling pathways that perturbed during disease progression
and could be useful as target to reverse the disease process. Post-translational
modification of non-histone proteins play crucial role to regulate energy metabolism
process in different cells including cardiomyocytes. The group is working to identify
how acetylation of proteins regulate certain cellular events like inflammation, ROS
generation, energy generation and mitochondrial dynamics. Data showed that
activation of SIRT1, a nuclear sirtuins, provides cardioprotection in diabetic heart via
deactylation of nuclear and mitochondrial proteins. Further, Biotechnology Department
is actively engaged to examine small molecules, plant-based and nutritional products
including vitamin D to screen them in different cardio-metabolic disease models.

1A. Post-translational modification of proteins and Sirtuins

Increased abundance of acetylated proteins during the progression of chronic
diseases is well-documented. Sirtuins, a group of protein deacetylases, play a
protective role in many diseases like cancer, diabetes and cardiovascular disease.
Absence of sirtuins can lead to hyperacetylation of both nuclear and mitochondrial
proteins leading to metabolic dysregulation. The post-translational modifications
(PTMs) of proteins can impair protein-protein interactions and may responsible for
complex phenotypic outcomes. Various PTM types such as acetylation, ubiquitination,
phosphorylation etc drive transcriptional regulation and metabolism, but such cross-
talks are poorly understood. In a recent study, Dr. Banerjee along with Dr. Amit Yadav
have integrated protein–protein interactions (PPI) and PTMs from several databases
to integrate information on 1,251 sirtuin-interacting proteins, of which 544 are
associated with cardiac diseases. The data showed that approximately 83% of the
sirtuin interactors contained at least one competitive crosstalk (in situ) site, with half of

the sites occurring in CVD-associated proteins (Figure 1). The group has identified
seven proteins (p53, LMNA, MAPT, ATP2A2, NCL, APEX1, and HIST1H3A)
containing disease-associated variants in PTM and crosstalk hotspots.

Further work is going on to identify the above proteins and their post-translational
modification in different cardiac disease models. One of the recent study with both in-
vitro cardiomyoblast cell and in-vivo animal model has revealed that p53 actylation is
linked to cardiac fibrosis. p53 nuclear translocation is mainly governed by acetylation

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