Life Sciences & Biotechnology
Title : | Evaluation of Sorcin dependent cytosolic retention of ChREBP and its application as a therapy for non-alcoholic fatty liver disease |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Mohan Kamthan, Jamia Hamdard, Delhi |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | kamthan.mohan@gmail.com |
Equipments : | UV- Visible Microplate reader
Pipette Set
UV Transilluminator |
Details
Executive Summary : | Non Alcoholic Fatty Liver disease (NAFLD) is a chronic disorder where there is excessive deposition of lipids in the liver without any history of alcohol abuse. Appallingly, despite its prevalence and serious consequences, no direct medicinal remedies are available for the treatment of fatty liver. Very recently using in vitro and in vivo approaches our group has shown that downregulation of sorcin, a cytosolic adaptor partner of ChREBP causes nuclear transactivation of ChREBP leading to dysregulated hepatic lipogenesis. We have also recently shown that NF?? mediated downregulation of sorcin contributes to diet-induced NAFLD (JBC, 2021). These studies present Sorcin as a pharmacological impetus for NAFLD. Gene delivery has been a recommended strategy for various monogenic ailments including liver diseases which are at an alarming state and worth immediate focus worldwide. Sorcin over-expression had also been implicated with drug resistance in cancer cells. However, Sorcin's role in drug resistance is heavily dependent on Ca2+ binding. On the contrary, Sorcin's interaction with ChREBP requires a low Ca2+ concentration. These findings suggest that Sorcin's role in lipogenesis and drug resistance are mutually exclusive events. In this project, we will thoroughly evaluate the Sorcin and ChREBP interaction by using a series of Sorcin mutants with compromised Ca2+ binding ability. We will also evaluate the role of these mutants in drug resistance. We will also attempt to develop an adenoviral construct using an albumin promoter for liver-specific expression of sorcin mutant. Finally, we will evaluate sorcin wt/mutant as a therapy in mouse NAFLD models. The outcomes of the study would be of high relevance for elusive fatty liver disease treatment. |
Co-PI: | Dr. Vikas Sood, Jamia Hamdard, Delhi-110062 |
Total Budget (INR): | 35,31,000 |
Organizations involved