Nassrin Dashti Hubbard, PhD

Dashti-HubbardNassrinProfessor

Dept. of Medicine
Division of Gerontology, Geriatrics and Palliative Care

Contact Information:

Office Address: BDB 680
Phone: 205-975-2159
E-mail: ndashti@uab.edu
Websites: School of Medicine Faculty Profile

Education:

University of Central Oklahoma, Edmond, OK 
BS , 1970

University of Oklahoma Health Science Center, Oklahoma City, OK 
PhD, 1976

Post-Graduate Training:

Oklahoma Medical Research Foundation, Oklahoma City, OK 
Postdoctoral Fellow, Cardiovascular Section, 1976-7

Oklahoma Medical Research Foundation, Oklahoma City, OK
Postdoctoral Fellow, Laboratory of Lipid and Lipoprotein Studies, 1977-9

Research Interests:

  • Structure and function of human apolipoprotein B (ApoB), the major apolipoprotein of plasma low density lipoproteins (LDL).
  • Mechanisms of assembly of ApoB- and ApoA-I-containing lipoproteins.
  • Nutritional and hormonal regulation of synthesis and secretion of lipoproteins in the liver and intestine.
  • Plasma lipid, lipoproteins and apolipoproteins and risk for age-related maculopathy (ARM).

Research Description:

Coronary artery disease (CAD) remains the leading cause of death in adults in the United States and other industrialized countries.  One of the strongest risk factors for CAD is the high levels of low density lipoprotein (LDL) cholesterol in plasma.  LDL, however, is the metabolic product of very-low density lipoproteins (VLDL).  VLDL are formed in the liver for the purpose of exporting the endogenously synthesized lipids, such as cholesterol and triglycerides, to the peripheral tissues.  In circulation, the remodeling and breakdown of VLDL by lipoprotein lipase results in the formation of atherogenic LDL. The major structural framework of the VLDL particle is provided by apolipoprotein B (ApoB).    ApoB has been a key target for study of cardiovascular disease for two main reasons. First, it has an obligatory role in the assembly and secretion of hepatic VLDL, therefore, increased production of ApoB promotes CAD and atherosclerosis.  Second, ApoB has an essential role in the receptor-mediated removal of plasma LDL, therefore, mutations and structural changes in ApoB that alter its recognition by the LDL receptor, lead to elevated concentration of LDL and increased risk for development of atherosclerotic diseases.  My research focuses on structure-function of ApoB which is essentially the only apoprotein moiety of atherogenic LDL.  My laboratory is specifically interested in delineating the mechanisms involved in the biogenesis of ApoB-containing lipoproteins, both at the cellular and subcellular levels.

While much attention has been given to LDL cholesterol, considerable evidence exists that other ApoB-containing lipoprotein species may be equal to or more important than LDL in the pathogenesis of atherosclerosis.  Related to this issue is the observation that the critical structural domains of ApoB that confer atherogenesity to ApoB-containing lipoproteins may be located within the N-terminal 48% of apoB-100 (the full-length protein), because ApoB-48-containing lipoproteins (the intestinally-derived chylomicrons) and ApoB-100-containing lipoproteins (formed in the liver) appear to be equally atherogenic in mouse models.  ApoB is a large amphipathic protein of 4,536 amino acid residues, is composed of five superdomains, and has a number of unusual features not found in other plasma apolipoproteins. The structural elements within the ApoB polypeptide that govern the lipid recruitment into a lipoprotein particle and subdomains that render ApoB atherogenic, however, are not well characterized. Therefore, it is important to understand fully the structure-function relationship of ApoB in order to develop strategies that might be effective in controlling the rate of hepatic synthesis, assembly and secretion of ApoB-containing lipoproteins, an important cause of hyperlipidemia and increased risk for CAD.


In summary, the goals of my research are to understand the mechanisms of the assembly of apoB-containing lipoproteins in hepatocytes and to define the intracellular steps in this process that can be altered.   On a broader scale, we are interested in the mechanisms involved in the regulation of VLDL and LDL production by fatty acids and insulin and the effects of these factors on the properties of atherogenic ApoB-containing lipoproteins. 

Publications

DRC Membership Category:

Senior Scientist