Protein metabolism is fundamental to cellular function, encompassing the continuous processes of protein synthesis, folding, transport, and degradation. Chaperones ensure that the newly synthesized proteins achieve their correct functional conformation. The protein synthesis machinery, proteasome, and autophagosome are vital for protein homeostasis within the cell. However, stress and aging can disrupt the homeostatic balance of proteins by impairing their clearance mechanisms, resulting in misfolding, accumulation, and cellular dysfunction. Defective protein folding, aggregation, and impaired clearance are hallmark features of human neurodegenerative disorders, cancers, and metabolic diseases. Our research aims to delineate the mechanism of protein misfolding, aggregation, and protein quality control systems in neurodegenerative diseases, particularly in Parkinson’s disease (PD).

The lab also addresses preterm birth, a major global health issue, by leading proteomics studies on pregnancy complications. In collaboration with THSTI, the group aims to discover early biomarkers for preeclampsia, preterm birth, and gestational diabetes mellitus. 

Proteostasis mechanism in Parkinson's disease

Parkinson’s disease (PD) manifests as a prevalent neurodegenerative disorder marked by motor neuron dysfunction, such as rigidity, resting tremor, and postural instability, stemming from the gradual loss of dopaminergic neurons in the midbrain, notably the substantia nigra. While most PD cases are sporadic, approximately 10% are familial, with several implicated genes, including α-synuclein, PINK1, Parkin, DJ-1, GBA1, UCHL1, VCP35, and LRRK2. Clinical and experimental data emphasize α-synuclein's pivotal role, with its increased expression, point mutations, and cytoplasmic accumulation in aging brains as significant risk factors. Neuroinflammation significantly contributes to PD progression, involving microglial activation and the release of pro-inflammatory molecules, exacerbating dopaminergic neuron degeneration. Mechanisms underlying neuroinflammation in PD, such as α-synuclein-induced microglial activation and oxidative stress, remain complex and multifaceted. The protein clearance system, encompassing the ubiquitin-proteasome system (UPS) and autophagy, is critical in mitigating misfolded protein aggregates implicated in PD pathogenesis. Dysfunction in these clearance mechanisms can lead to aggregate accumulation and subsequent neurodegeneration. Therapeutic strategies targeting protein clearance pathways offer potential avenues for PD treatment, though further research is imperative to comprehend their intricate interplay and develop effective interventions. Our research aims to elucidate protein aggregation mechanisms and their impact on PD progression.

Inter-organ communication in Parkinson’s disease

Inter-organ crosstalk in Parkinson's disease (PD) involves dynamic bidirectional communication between various organs and systems, influencing disease onset and progression. While PD is primarily recognized as a neurodegenerative disorder affecting the central nervous system (CNS), emerging evidence highlights the significant role of peripheral organs, including the gut, liver, skeletal muscle, heart, and immune system in its pathogenesis. Our laboratory employs transgenic mice models and human patient studies to investigate the molecular mechanisms underlying this inter-organ communication, aiming to unravel disease pathology and progression.

Biomarker discovery in Pregnancy complications

Preterm birth stands as a significant global public health challenge, representing the primary cause of neonatal mortality. India accounts for approximately a quarter of global preterm births and related deaths. From a clinical standpoint, comprehending the molecular mechanisms underlying preterm birth is imperative for early prediction and prevention. RCB collaborates with THSTI, NIBMG, Gurugram General Hospital, and several other institutions for the Inter-institutional Advanced Research on Birth Outcome-DBT India Initiative (GARBH-Ini), with our team leading the proteomics component. Moreover, our involvement in the global Multi-Omics for Mothers and Infants (MOMI) Consortium allows us to address diverse inquiries related to pregnancy complications. At the heart of our endeavors lies the overarching objective of pinpointing biomarkers crucial for early preterm birth detection