Investigating the role dysfunctional high density lipoprotein (HDL) as a risk factor in cardiovascular and cerebrovascular diseases and alterations to the HDL lipoproteome
The overarching goal of this project is to determine changes to the HDL that render it dysfunctional from a mechanistic perspective.
We determine the effect of age- and environment-related oxidative modification on the structure and function of apoE, apoAI and other HDL related proteins and the consequences on lipoprotein metabolism.
The brain enjoys several metabolic, immunological and biochemical privileges due to the presence of the blood brain barrier. However, the integrity of the barrier is compromised as a result of age-related oxidative stress, with increased permeability across the blood brain barrier (BBB). In this context, we also examine the molecular basis of the effect of oxidative modification of HDL on the permeability and integrity of the BBB under normal physiological and pathological conditions.
We determine the effect of age- and environment-related oxidative modification on the structure and function of apoE, apoAI and other HDL related proteins and the consequences on lipoprotein metabolism.
The brain enjoys several metabolic, immunological and biochemical privileges due to the presence of the blood brain barrier. However, the integrity of the barrier is compromised as a result of age-related oxidative stress, with increased permeability across the blood brain barrier (BBB). In this context, we also examine the molecular basis of the effect of oxidative modification of HDL on the permeability and integrity of the BBB under normal physiological and pathological conditions.
Evaluating use of HDL as a drug delivery and targeting vehicle using reconstituted HDL as a “nanovehicle” or “Trojan Horse”
This project involves the design of HDL containing apoE as a nanosized “Trojan horse” for targeted delivery of therapeutic molecules and drugs across the blood brain barrier to the brain.
Examining lipid-binding mechanism and lipid-associated conformation of apoE isoforms using fluorescence and other biophysical approaches
The objective of this project is to examine the isoform-specific differences in lipid- and beta-amyloid-binding mechanism and lipid-associated conformation of apoE and to understand the molecular basis of its function in lipid-free, lipoprotein- and proteoglycan-bound states using chimeras and hybrids.