Learning the homeostasis processes by virtue of multi-organ cross-talks in metabolic disorders
Summary of Research:
The basic idea of our research is based on the fact that nothing works in isolation and in the functioning of a body the integrative cross-talk among multi-organs is a must. We trust in the amazing capacity of the body to adjust to the insults/adverse conditions to maintain homeostasis. So far, the role of individual organs or cells has been the major focus of research. However, the detailsof how multiorgan’scommunicate and maintain homeostasis arelargely unknown. Thus, there exists a tremendous scope to learnand discover novel processes. Here at NII, our laboratory is actively involved in understanding such communication processes among multi-organs using the mouse genetic models of obesity and associated metabolic diseases like diabetes, inflammatory bowel diseases, etc.
Broadly, our group is involved in learning about the following areas:
1. How do multi-organs communicate in high-fat diet-induced metabolic disorders like diabetes and inflammatory bowel diseases?
2. What are the messenger molecules (biofactors and/or hormones) that effectuate metabolic homeostasis?
3. Could organ-specific targeting be established as a better therapeutic platform for metabolic diseases?
Chayanika Gogoi (Ph.D. Student), Mohammad Athar Mehraj (Ph.D. Student), Shubham Sharma (JRF), Pankaj Kumar (Technician)
1. Dipeptidyl Peptidase-IV (DPP4) Inhibitors, Methods, and Compositions for Suppressing Adipose Tissue Inflammation, Dr. Ira Tabas, Dr. Devram Sampat Ghorpade, Dr. LaleOzcan, U.S. Provisional Patent Application No:62/120,549, 2015.
- Ozcan, L., Ghorpade, D. S., and I. Tabas. "Targeting Soluble Dpp-4 for Insulin Resistance: Origin Matters." J Clin Endocrinol Metab (Dec 4 2020). http://dx.doi.org/10.1210/clinem/dgaa902.
- Ghorpade, D. S., L. Ozcan, Z. Zheng, S. M. Nicoloro, Y. Shen, E. Chen, M. Bluher, M. P. Czech, and I. Tabas. "Hepatocyte-Secreted Dpp4 in Obesity Promotes Adipose Inflammation and Insulin Resistance." Nature 555, no. 7698 (Mar 29 2018): 673-77. http://dx.doi.org/10.1038/nature26138.
- Ozcan, L., Ghorpade, D. S., Z. Zheng, J. C. de Souza, K. Chen, M. Bessler, M. Bagloo, B. Schrope, R. Pestell, and I. Tabas. "Hepatocyte Dach1 Is Increased in Obesity Via Nuclear Exclusion of Hdac4 and Promotes Hepatic Insulin Resistance." Cell Rep 15, no. 10 (Jun 7 2016): 2214-25. http://dx.doi.org/10.1016/j.celrep.2016.05.006.
- Fredman, G., N. Kamaly, S. Spolitu, J. Milton, Ghorpade,D. S., R. Chiasson, G. Kuriakose, M. Perretti, O. Farokzhad, and I. Tabas. "Targeted Nanoparticles Containing the Proresolving Peptide Ac2-26 Protect against Advanced Atherosclerosis in Hypercholesterolemic Mice." Sci Transl Med 7, no. 275 (Feb 18 2015): 275ra20. http://dx.doi.org/10.1126/scitranslmed.aaa1065.
- Ozcan, L., X. Xu, S. X. Deng, Ghorpade, D. S., T. Thomas, S. Cremers, B. Hubbard, M. H. Serrano-Wu, M. Gaestel, D. W. Landry, and I. Tabas. "Treatment of Obese Insulin-Resistant Mice with an Allosteric Mapkapk2/3 Inhibitor Lowers Blood Glucose and Improves Insulin Sensitivity." Diabetes 64, no. 10 (Oct 2015): 3396-405. http://dx.doi.org/10.2337/db14-1945.
- Prakhar, P., S. Holla, Ghorpade,D. S., M. Gilleron, G. Puzo, V. Udupa, and K. N. Balaji. "Ac2pim-Responsive Mir-150 and Mir-143 Target Receptor-Interacting Protein Kinase 2 and Transforming Growth Factor Beta-Activated Kinase 1 to Suppress Nod2-Induced Immunomodulators." J Biol Chem 290, no. 44 (Oct 30 2015): 26576-86. http://dx.doi.org/10.1074/jbc.M115.662817.
- Subramanian, M., L. Ozcan, Ghorpade, D. S., A. W. Ferrante, Jr., and I. Tabas. "Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity." PLoS One 10, no. 8 (2015): e0135842. http://dx.doi.org/10.1371/journal.pone.0135842.
- Holla, S., Ghorpade,D. S., V. Singh, K. Bansal, and K. N. Balaji. "Mycobacterium Bovis Bcg Promotes Tumor Cell Survival from Tumor Necrosis Factor-Alpha-Induced Apoptosis." Mol Cancer 13 (Sep 11 2014): 210. http://dx.doi.org/10.1186/1476-4598-13-210.
- Ghorpade, D. S., S. Holla, S. V. Kaveri, J. Bayry, S. A. Patil, and K. N. Balaji. "Sonic Hedgehog-Dependent Induction of Microrna 31 and Microrna 150 Regulates Mycobacterium Bovis Bcg-Driven Toll-Like Receptor 2 Signaling." Mol Cell Biol 33, no. 3 (Feb 2013): 543-56. http://dx.doi.org/10.1128/MCB.01108-12.
- Ghorpade, D. S., S. Holla, A. Y. Sinha, S. K. Alagesan, and K. N. Balaji. "Nitric Oxide and Klf4 Protein Epigenetically Modify Class Ii Transactivator to Repress Major Histocompatibility Complex Ii Expression During Mycobacterium Bovis Bacillus Calmette-Guerin Infection." J Biol Chem 288, no. 28 (Jul 12 2013): 20592-606. http://dx.doi.org/10.1074/jbc.M113.472183.
- Ghorpade, D. S., A. Y. Sinha, S. Holla, V. Singh, and K. N. Balaji. "Nod2-Nitric Oxide-Responsive Microrna-146a Activates Sonic Hedgehog Signaling to Orchestrate Inflammatory Responses in Murine Model of Inflammatory Bowel Disease." J Biol Chem 288, no. 46 (Nov 15 2013): 33037-48. http://dx.doi.org/10.1074/jbc.M113.492496.
- Ghorpade, D. S., R. Leyland, M. Kurowska-Stolarska, S. A. Patil, and K. N. Balaji. "Microrna-155 Is Required for Mycobacterium Bovis Bcg-Mediated Apoptosis of Macrophages." Mol Cell Biol 32, no. 12 (Jun 2012): 2239-53. http://dx.doi.org/10.1128/MCB.06597-11.
- Bansal, K., A. Y. Sinha, Ghorpade, D. S., S. K. Togarsimalemath, S. A. Patil, S. V. Kaveri, K. N. Balaji, and J. Bayry. "Src Homology 3-Interacting Domain of Rv1917c of Mycobacterium Tuberculosis Induces Selective Maturation of Human Dendritic Cells by Regulating Pi3k-Mapk-Nf-Kappab Signaling and Drives Th2 Immune Responses." J Biol Chem 285, no. 47 (Nov 19 2010): 36511-22. http://dx.doi.org/10.1074/jbc.M110.158055