Dr. Vasanthy Narayanaswami
Associate Professor of Biochemistry (2008)
Biochemistry, Biophysics, Neurobiology, Molecular Spectroscopy, Cell Biology
Teaching: Biochemistry CHEM 441A, 441B, 541 and 542 (Special Topics in Lipids & Lipoproteins); Research classes CHEM 496, 697, 698
Research Laboratory: MLSC-243
Brief BiosketchPhD, Indian Institute of Technology (Madras), Chennai, India
Post doctoral fellow, Alexander von Humboldt fellow, University of Dusseldorf, Germany
Post doctoral fellow, University of Alberta, Edmonton, Canada
Associate Scientist, Children.s Hospital Oakland Research Institute, Oakland, CA
News alert!2014 CSULB Outstanding Research and Creative Activity by a Graduate Student (Roy Hernandez)
2014 CSULB Outstanding Faculty Mentor for Student Engagement in Research Award (Vas)
2014 Women & Philanthropy Award (Charina Fabilane)
2014 CSUPERB-Howell Research Scholar Award
Area of research: Apolipoprotein E and Cholesterol Transport in Aging and Disease Disease
Our research work involves investigating the role of apolipoprotein E (apoE) in cardiovascular disease and Alzheimer.s disease. We study its role in relation to cholesterol transport in the vascular and the central nervous system (CNS), especially in age-related neurodegenerative diseases such as Alzheimer.s disease (AD). We employ a combination of biochemical, biophysical and cell biological approaches to address these issues. The following are the main projects in my group:
- Structural and conformational analyses of apolipoproteinE (apoE)
- Age- and environment-related oxidative stress and apoE
- Evaluate use of HDL with apoE as a vehicle for delivery of flavonoids across the blood brain barrier
- Role of apoE in cholesterol transport and metabolism at the neurovascular junction
- ApoE in Alzheimer’s disease and cerebral amyloid angiopathy
We are actively seeking candidates interested in pursuing graduate work in state-of-the-art biochemical, biophysical and cell biological research areas of direct biomedical relevance. Motivated undergraduate students showing a strong and promising potential for research are strongly encouraged to participate in our research projects.
RESEARCH DETAILSStructural and conformational analyses of apoE
ApoE3 is a 34-kDa exchangeable apolipoprotein that plays a crucial role in cholesterol transport and metabolism in the vasculature and the CNS. A polymorphic protein, apoE4 is considered a risk factor for Alzheimer.s disease and heart disease. We perform structural and conformational analyses of apoE isoforms employing fluorescence spectroscopy and other biophysical approaches to understand the molecular basis of its function. We employ fluorescence resonance energy transfer and exploit the unique fluorescence features of pyrene to obtain structural information about apoE.
Age- and environment-related oxidative stress and apoE
This project involves examining the effect of acrolein on the structure and function of apoE and the consequences in lipoprotein metabolism. Acrolein is a pro-oxidant that is generated as a metabolite of age-related oxidative stress and is present in high concentrations in the gaseous phase of tobacco smoke. The goal of this project is to determine if exposure to second hand smoke predisposes individuals towards developing a pro-atherogenic profile, an established risk factor for heart disease and stroke.
Evaluate use of HDL with apoE as a .nanovehicle. for delivery of bioflavonoids and therapeutic agents across the blood brain barrier
This project involves the design of HDL containing apoE as a nanosized .Trojan horse. to deliver bioflavonoids across the blood brain barrier (BBB) to the brain. We are examining the use of HDL bearing anti-inflammatory and anti-amyloid bioflavonoids as a potential therapeutic agent to treat or intervene Alzheimer.s disease.
Role of apoE in cholesterol transport and metabolism at the neurovascular junction 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 barrier. We study the role of apoE in maintaining the integrity of the barrier, with cholesterol being a significant factor in this function. We examine the effect of oxidative stress on the permeability of the barrier under normal physiological and pathological conditions.
ApoE in Alzheimer.s disease and cerebral amyloid angiopathy One of the hallmark features of Alzheimer.s disease is the aggregation of the amyloid beta peptide (A.) in the brain parenchyma and in the cerebral microvasculature. This project involves study of the isoform-specific role of apoE4 in predisposing individuals towards Alzheimer.s disease. We examine the sites of interaction of A. on apoE, apoE isoform-specific differences in binding A., effect of lipidation on binding. We employ an inter-disciplinary approach involving molecular biology, molecular spectroscopy (high resolution fluorescence spectroscopy), protein chemistry and cell biology to address these issues. In a collaborative effort with Dr. Vincent Raussens and Dr. Jean-Marie Ruysschaert, Free University, Brussels, Belgium, the structural basis of the toxicity associated with oligomeric A. and apoE4 are evaluated using infrared analysis.
Kim, S. H., Cruz, S., Adhikari, B. B., Schramm, M. P., Vinson, J. A. & Narayanaswami, V. (2015) Targeted Intracellular Delivery of Resveratrol to Glioblastoma Cells using Apolipoprotein E-Containing Reconstituted HDL as a Nanovehicle. PLoS ONE 10(8): e0135130. doi:10.1371/journal.pone.0135130
Kim, S. H., Kothari, S., Patel, A. B., Bielicki, J. K. & Narayanaswami, V. (2014) A Pyrene Based Fluorescence Approach to Study Conformation of Apolipoprotein E3 in Macrophage-generated Nascent High Density Lipoprotein. Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2014.05.071. [Epub ahead of print]
Tran, T. N., Kosaraju, M. G., Tamamizu-Kato, S., Akintunde, O., Zheng, Y., Bielicki, J. K., Pinkerton, K, Uchida, K., Lee, Y. Y. & Narayanaswami, V. (2014) Acrolein Modification Impairs Key Functional Features of Rat Apolipoprotein E: Identification of Modified Sites by Mass Spectrometry. Biochemistry 53, 361-375 (PMCID # PMC3937454).
Zheng, Y., Patel, A. B., Narayanaswami, V. & Bielicki, J. K. (2013) Retention of .-helical structure by HDL mimetic peptide ATI-5261 upon extensive dilution represents an important determinant for stimulating ABCA1 cholesterol efflux with high efficiency. Biochem. Biophys. Res. Commun. 441, 71-76 (PMID # 24129191- PubMed In Process).
Tran, T. N., Kim, S. H., Gallo, C., Amaya, M., Kyees, J. and Narayanaswami, V. (2013) Biochemical and Biophysical Characterization of Recombinant Rat Apolipoprotein E: Similarities to Human Apolipoprotein E3. Arch. Biochem. Biophys. 259, 18-25 (PMCID: PMC3543869)
Zheng, Y., Kim, S. H., Patel, A. B., Narayanaswami, V, Iavarone, A. T., Hura, G. L. & Bielicki, J. K. (2012) The positional specificity of EXXK motifs within an amphipathic .-helix dictates preferential lysine modification by acrolein: Implications for the design of high-density lipoprotein mimetic peptides. Biochemistry DOI 10.1021/bi300626g
Bains, G. K., Kim, S. H., Sorin, E. J. and Narayanaswami, V. (2012) Extent of pyrene excimer fluorescence emission is a reflector of distance and flexibility: Analysis of the segment linking the LDL Receptor-binding and tetramerization domains of apolipoprotein E3. Biochemistry DOI: 10.1021/bi3005285
Bains, G., Patel, A. B. and Narayanaswami, V. (2011) Pyrene: A probe to study protein conformation and conformational changes. Molecules 16, 7909-7935
Zheng, Y.,* Patel A. B.*, Narayanaswami, V., Hura, G. L., Hang, B., and Bielicki, J. K. (2011) HDL mimetic peptide ATI-5261 forms an oligomeric assembly in solution that dissociates to monomers upon dilution. Biochemistry 50, 4068-4076 (*equal contribution)
Khumsupan, P., Ramirez, R., Khumsupan, D. and Narayanaswami, V. (2011) Apolipoprotein E LDL
receptor-binding domain-containing high-density lipoprotein: A nanovehicle to transport curcumin, an
antioxidant and anti-amyloid bioflavonoid. Biochim Biophys Acta 1808, 352-359.
Hauser, P. S., Narayanaswami, V. and Ryan, R. O. (2011) Apolipoprotein E: From lipid transport to neurobiology. Prog. Lipid Res. 50, 62-74.
Narayanaswami, V., Kiss, R. S. and Weers, P. M. (2010) The helix bundle: a reversible lipid binding motif. Comparative Biochem. Physiol. A Mol. Integr. Physiol. 155, 123-133.
Bielicki, J. K., Zhang, H., Cortez, Y., Narayanaswami, V., Patel, A. B., Johansson, J. and Azhar, S. (2010) A new HDL mimetic peptide that stimulates cellular cholesterol efflux with high efficiency greatly reduces atherosclerosis in mice. J. Lipid Res. 51, 1496-1503.
Patel, A. B., Khumsupan, P. and Narayanaswami, V. (2010) Pyrene Fluorescence Analysis Offers New Insights into the Conformation of the Lipoprotein-Binding Domain of Human Apolipoprotein E. Biochemistry 49, 1766-1775.
Crutcher, K. A., Lilley, H. N., Anthony, S. R., Zhou, W. and Narayanaswami, V. (2010) Full-length apolipoprotein E protects against the neurotoxicity of an apoE-related peptide. Brain Research 1306, 106-115.
Cerf, E., Sarroukh, R., Tamamizu-Kato, S., Derclaye, S., Dufrêne, Y., Narayanaswami, V., Goormaghtigh, E., Ruysschaert, J.-M. and Raussens, V. (2009) Anti-parallel beta-sheet - A signature structure of the oligomeric amyloid-beta peptide. Biochemical J. 421, 415-423.
RELEVANT LINKSAlexander von Humboldt Foundation: http://www.humboldt-foundation.de/web/home.html
American Heart Association: http://www.americanheart.org
The movers and shakers in Vas Lab
Vas Lab members, June 2014 Beach Party