- 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.
- 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 rhthyms, to modulate lipid
metabolism in the liver, intestine and macrophages.
- We have identfied different miroRNAs and other long non-coding RNAs that regulate
assmebly and secertion of apoB-containing lipoproteins. We are in the process of elucidating
moelcular mechansims involved in these regulations and evaluating their therapeutic
potentials to lower plasma lipids and atherosclerosis. The two cartoons depict our
workign models about the roel of miR-30c and miR-1200 in the regulation of lipid metabolism
- We are trying to understand the role of MTP in different tissues, such as liver, intestne,
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. Few representative publications are:
- 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. Nat. 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. Nat. Communs. In press.