M. Mahmood Hussain, Ph.D.
Endowed Chair & Director Basic Science,
Director, Diabetes and Obesity Center
1. Our laboratory focuses on lipid transport and lipoprotein assembly to find new ways of treating hyperlipidemias and atherosclerosis. We have described two pathways (chylomicron (CM) and HDL) of lipid absorption and are evaluating the role of different proteins in these two pathways. The major emphasis is on the role of microsomal triglyceride transfer protein (MTP) in lipid absoprtion and lipoprotein assmbely.
2. We study the regulation of lipoportein assembly and lipid absorption by circadian rhthyms. We identified SHP, USF2 and GATA4 as clock controlled genes that are regulated by Clock and Bmal1, two master regulators of circadian rhythms, to modulate lipid metabolism in the liver, intestine and macrophages.
3. We have identfied different microRNAs and other long non-coding RNAs that regulate assembly and secretion of apoB-containing lipoproteins. We are in the process of elucidating molecular mechanisms involved in these regulations and evaluating their therapeutic potentials to lower plasma lipids and atherosclerosis. The two cartoons depict our working models about the role of miR-30c and miR-1200 in the regulation of lipid metabolism and atherosclerosis.
4. We are trying to understand the role of MTP in different tissues, such as liver, intestine, brain and pancreas.
Since 2001, besides several postdoctoral fellows and visiting scientists, three MD, PhD and four PhD students have graduated from the lab. Currently (2016), three PhD students are pursuing their degrees.
- Pan X, Zhang Y, Wang L, and Hussain MM (2010) Diurnal regulation of MTP and plasma lipid by Clock is mediated by SHP. Cell Metabolism. 12:174-186.
- Khatun I, Zeissig S, Iqbal J, Wang M, Curiel D, Shelness GS, Blumberg RS, Hussain MM (2012) Phospholipid transfer activity of microsomal triglyceride transfer protein produces apolipoprotein B and reduces hepatosteatosis while maintaining low plasma lipids in mice. Hepatology, 55:1356-1368.
- Soh J, Iqbal J, Queiroz J, Fernandez-Hernando C, Hussain MM (2013) MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Med. 19:892-900.
- Iqbal J, Walsh MT, Hammad SM, Cuchel M, Tarugi P, Hegele RA, Davidson NO, Rader DJ, Klein RL, Hussain MM, (2015) Microsomal triglyceride transfer protein transfers and determines plasma concentrations of ceramide and sphingomyelin but not glycosylceramide. J Biol Chem. 290:25863-25875.
- Pan X, Bradfield CA, Hussain MM, (2016) Global and hepatocyte-specific ablation of Bmal1 induces hyperlipidemia and enhances atherosclerosis. Communs. 7:13011. PMID: 27721414.