Personal Statement

Research in the P. K. Shah Laboratory focuses on:

• The genetic, molecular, biochemical and cellular mechanisms of atherosclerotic plaque formation
• The development of novel therapies for inhibition, stabilization and regression of atherosclerosis
• The bioengineering of blood vessels
• The optimal diagnostic protocols for early detection of subclinical heart disease

As director of the Oppenheimer Atherosclerosis Research Center at Cedars-Sinai and PI of the Prediman Krishan (P. K.) Shah Laboratory, I am leading several studies that focus on heart disease prevention and treatment. Our lab has discovered the atheroprotective and atheroregressive effects of recombinant mutant apolipoprotein (ApoA-I Milano) and led its development into a therapeutic strategy. We developed the concept of immunomodulation of atherosclerosis using oxidized LDL and ApoB-100-related peptide antigens in a vaccination strategy against atherosclerosis, aortic aneurysm and hypertension. The P. K. Shah Lab has established the concept that macrophages and metalloproteinases contribute to plaque rupture and thrombosis.

My current investigations include:

• The role of novel genes (tenascin, pleiotrophin, GATA3 and KLF14) in atherosclerosis, plaque neovascularity, intraplaque hemorrhage and metabolic syndrome/obesity
• The potential role of ApoB-100 peptide based vaccines in modulation of atherosclerosis, hypertension and aortic aneurysm
• Gene transfer of ApoA-I Milano using AAV vectors for atherosclerosis regression
• Evaluation of transcriptional regulation of macrophage phenotype specifically examining the role of GATA3 in macrophage function

The P. K. Shah Laboratory is also evaluating the potential benefits of ApoA-1 Milano gene transfer for Alzheimer’s disease using animal models in collaboration with the Koronyo-Hamaoui Laboratory.