Aparna Lakkaraju, PhD

Portrait of Aparna Lakkaraju, PhD
Assistant Professor
Ophthalmology and Visual Sciences
Address: 
SMI 677a
1300 University Ave
Madison, WI 53706
Telephone: 
(608) 263-6176
Focus Groups: 
Neuroscience/Neuropathology
Education: 
PhD, Pharmaceutics, University of Minnesota, Minneapolis
Post-doctoral, Ophthalmology and Cell Biology, Cornell University Weill Medical College, New York
Research Summary: 
Cellular basis of retinal degenerative diseases such as inherited and age-related macular degenerations, drug discovery, epithelial cell biology, cholesterol metabolism, high-resolution & high-speed live imaging
Research Detail: 

Work in our laboratory is focused on understanding the cellular basis of retinal diseases like age-related macular degeneration (AMD), the most common cause of progressive vision loss among older adults worldwide. We study the retinal pigment epithelium (RPE), a monolayer of post-mitotic epithelial cells that forms the outermost layer of the retina and performs many functions that are indispensable for vision. It is now believed that over a lifetime, damage to the RPE coupled with genetic and environmental factors predispose a person towards developing AMD. However, AMD is a multifactorial disease, and elucidating the cascade of events that leads to vision loss has proven elusive. Our published work shows that RPE cells accumulate high levels of cholesterol under conditions that recapitulate certain features of AMD. Cholesterol homeostasis within cells is tightly controlled because excess cholesterol interferes with intracellular trafficking of proteins and lipids and inhibits basic housekeeping functions like lysosomal degradation, autophagy and secretion. Chronic disruption of these functions critically damages cell health.

Our current research has two main goals:

  1. to elucidate the pathogenesis of retinal degenerations at the cellular level using biochemistry, cell biology and high-speed live microscopy of healthy, aging and diseased RPE (from human donors, non-human primates, rodents and pigs)
  2. to use this information to identify novel drug targets and investigate whether existing drugs like statins can help preserve vision in the aging or diseased retina.
Selected Publications: 
Lakkaraju, A. Endo-lysosome function in the retinal pigment epithelium in health and disease. Advances in Experimental Medicine and Biology, 723: 723-9, 2012
Lakkaraju, A., J.M. Carvajal-Gonzalez and E. Rodriguez-Boulan. It takes two to tango to the melanosome. Journal of Cell Biology 187: 2161-63, 2009. PMCID: PMC2768836
Thorne, R. G., A. Lakkaraju, E. Rodriguez-Boulan and C. Nicholson. In vivo protein diffusion in brain extracellular space regulated by interactions with heparan sulfate. Proceedings of the National Academy of Sciences USA, 105: 8416-21, 2008. PMCID: PMC2448851
Lakkaraju, A. and E. Rodriguez-Boulan. Itinerant exosomes: emerging roles in cell and tissue polarity. Trends in Cell Biology 18: 199-209, 2008. PMID: 18396047
Lakkaraju, A., S. C. Finnemann and E. Rodriguez-Boulan. The lipofuscin fluorophore perturbs cholesterol metabolism in retinal pigment epithelial cells. Proceedings of the National Academy of Sciences USA 104: 11026-11031, 2007. PMCID: PMC1904145
Lakkaraju, A. and E. Rodriguez-Boulan. Caught in the traffic. Nature 448: 266-267, 2007. PMID: 17637651
Perret, E.*, A. Lakkaraju*, S. Deborde, R. Schreiner and E. Rodriguez-Boulan. Evolving endosomes: How many varieties and why? Current Opinion in Cell Biology 17: 423-34, 2005. PMID:1597578
Lakkaraju, A., Y. E. Rahman and J. M. Dubinsky. Low-density lipoprotein receptor-related protein mediates the endocytosis of anionic liposomes in neurons. Journal of Biological Chemistry 277: 15085-15092, 2002. PMID: 11830589
Lakkaraju, A., J. M. Dubinsky, W. C. Low and Y. E. Rahman. Neurons are protected from excitotoxic death by p53 antisense oligonucleotides delivered in anionic liposomes. Journal of Biological Chemistry 276: 32000-32007, 2001. PMID: 11406618