189 - Mice, Macrophages, and Metabolism: Browning Keeps Obesity at Bay

In this episode, we discuss the very early stages of drug targets and drug development with Dr. Mohd Shahid, PhD. Dr. Shahid’s research involves the IER3 gene, which is an important modulator of the body’s inflammatory response via its action in major immune cells, including macrophages and T-cells, and plays a role in metabolic disorders such as obesity, diabetes, and atherosclerosis, revealing a previously unknown function of this protein.

Key Concepts

1. Drug development is a multi-decade journey – human clinical trials occur very late in the process. Drug development often starts before a drug molecule is even conceived by identifying potential drug targets.
2. Chronic inflammation is important for a variety of diseases, including obesity and atherosclerosis. Dr. Shahid’s work focuses on a specific gene, Immediate Early Response 3 Gene (IER3 or IEX-1), and its role in modulating the inflammatory response in these disease states.
3. The research process frequently leads to unexpected discoveries and new lines of inquiry. With Dr. Shahid, his work in obesity and inflammation actually led to a new understanding of the IER3’s role in the interplay between macrophages, inflammation, and energy expenditure.

References

• Shahid M, Javed AA, Chandra D, et al. IER3 deficiency induces browning of white adipose tissue and resists diet-induced obesity. Sci Rep. 2016;6:24135. Published 2016 Apr 11. doi:10.1038/srep24135
• Shahid M, Hermes EL, Chandra D, et al. J Am Heart Assoc. 2018;7:e009261. DOI: 10.1161/JAHA.118.009261.
• Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. doi:10.1056/NEJMoa0807646
• Tardif JC, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381(26):2497-2505. doi:10.1056/NEJMoa1912388