Research Projects

Rationale: Nutritional status profoundly influences immune function and metabolism. Both undernourishment and obesity are associated with increased risk of infections, including tuberculosis (TB), due to altered inter-organ communication. Organokines—secreted proteins from tissues such as adipose, liver, gut, and muscle—regulate systemic physiology. Despite their significance, little is known about their baseline levels in different nutritional states, especially in Indian populations where TB and malnutrition are highly prevalent. A major limitation in studying organokines is their low abundance in plasma, making detection difficult with traditional mass spectrometry. This study will use advanced proteomic methods, SWATH-MS and MRM, to achieve sensitive, high-throughput quantification of plasma organokines. This will help uncover disease-associated signatures and clarify mechanistic links between nutritional status, metabolism, and TB pathogenesis. Objective: To establish baseline organokine profiles in Indian cohorts across BMI categories and in TB patients; and to investigate the role of specific organokines in metabolic regulation and immune responses. Hypothesis: We hypothesize that dysregulated expression of organokines plays a central role in the pathogenesis of malnutrition and tuberculosis, contributing to metabolic imbalance and energy homeostasis leading to wasting syndrome. Furthermore, we propose that advanced mass spectrometry-based methods, such as SWATH-MS and MRM, will enable the sensitive and accurate quantification of these low-abundance organokines from small plasma volumes. By establishing distinct organokine profiles, we expect to identify early biomarkers that correlate with disease severity and therapeutic outcomes, thereby offering new insights into inter-organ communication during diseases, and offering a way towards better combination therapy. Main Experiments: This project integrates clinical, in vitro, and exploratory in vivo analyses. Plasma samples from BMI-stratified healthy individuals and TB patients will undergo SWATH-MS-based untargeted profiling, followed by MRM validation of key proteins. Functional validation will involve recombinant organokines tested on adipocytes, hepatocytes, myoblasts, and macrophages to assess effects on lipid metabolism, cytokine production, and molecular pattern of other pathways. Impact: 1-Develop high-resolution plasma proteomic methodology. 2-Establish India-specific organokine baselines. 3-Link organokine profiles to nutritional status and tissue-specific metabolic responses. 4-Generate TB-specific profiles for preliminary biomarker discovery, tools can be extended to extrapulmonary TB studies.