Aparna Lakkaraju, PhD • UCSF Profiles

Research in the Lakkaraju laboratory builds on fundamental insights from retinal cell biology to develop effective therapies for inherited and age-related macular degenerations (AMD). These diseases destroy central high-resolution vision in over 30 million people globally and have limited therapeutic options.

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We study the retinal pigment epithelium (RPE), which performs numerous functions indispensable for vision, and is a key site of injury in macular degenerations. Current areas of research focus include: 1. Autophagy and extracellular vesicles in the RPE; 2.Mitochondrial dynamics, metabolic stress and inflammation in the retina; 3. The role of complement activation in AMD; 4. Biophysical approaches to understanding the genetic basis of AMD; and 5. Novel drug targets for macular degenerations. Using advanced live imaging of the RPE and retina, we recently identified promising FDA-approved drugs that can be repositioned to treat macular degenerations (U.S. Patent P140282US01).

Awards

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Lorraine Maresca Innovative Research Award, BrightFocus Foundation, 2021-2024
Lorraine Maresca Innovative Research Award, BrightFocus Foundation, 2021-2024
Catalyst Award for Innovative Approaches to Age-Related Macular Degeneration, Research to Prevent Blindness Foundation, 2019-2022
Charlotte & Alexander Danilevsky Award for Macular Degeneration Research, BrightFocus Foundation, 2015-2018
New Investigator Award, Wisconsin Partnership Program, 2015-2017
Rebecca Meyer Brown Professorship, Retina Research Foundation, 2012-2018
Career Development Award, Research to Prevent Blindness, 2010-2014
Ruth L. Kirchstein F32 Individual Post-Doctoral Fellowship Award, National Eye Institute, 2003-2006

Education & Training

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Post-doctoral Training Ophthalmology & Cell Biology Cornell University Weill Medical College
PhD Pharmaceutical Sciences University of Minnesota

Interests

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Age-related macular degeneration
Retinal pigment epithelium
Mitochondrial dynamics
Stargardt disease
Cholesterol and lipid metabolism
Extracellular vesicles
Retinal cell biology
Live-cell imaging of the retina
Complement activation and inflammation
Autophagy

Grants and Projects

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Mechanisms of RPE dysfunction in macular degenerations: role of intracellular complement activation, NIH, 2020-2025
Novel Approaches to Identify Tipping Points and Therapeutic Targets for Early AMD, Research to Prevent Blindness, 2019-2022
Mechanisms of cellular clearance in the retinal pigment epithelium, NIH, 2015-2021
Modulating Mitochondrial Dynamics in the Retinal Pigment Epithelium as a Therapeutic Strategy for Macular Dystrophies, Macular Society UK, 2015-2019
Can RPE-derived Exosomes Contribute to Subretinal Drusenoid Deposits?, BrightFocus Foundation, 2015-2018
Lysosome function and autophagy in age-related macular degeneration, American Federation for Aging Research, 2013-2015
Role of Cholesterol Homeostasis in Macular Degeneration, NIH, 2003-2006

Publications (42)

Top publication keywords:
MitochondriaComplement C3aCeramidesSphingomyelin PhosphodiesteraseApolipoprotein E2CholesterolEndosomesMultiple System AtrophyRetinal Pigment EpitheliumOrganellesMacular DegenerationLysosomesSequestosome-1 ProteinComplement Membrane Attack ComplexComplement System Proteins

How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.
Experimental eye research 2024 Lakkaraju A, Boya P, Csete M, Ferrington DA, Hurley JB, Sadun AA, Shang P, Sharma R, Sinha D, Ueffing M, Brockerhoff SE
Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration.
bioRxiv : the preprint server for biology 2024 Yu A, Tan LX, Lakkaraju A, Santina LD, Ou Y
Targeting complement C3a receptor resolves mitochondrial hyperfusion and subretinal microglial activation in progranulin-deficient frontotemporal dementia.
bioRxiv : the preprint server for biology 2024 Tan LX, Oertel FC, Cheng A, Cobigo Y, Keihani A, Bennett DJ, Abdelhak A, Montes SC, Chapman M, Chen RY, Cordano C, Ward ME, Casaletto K, Kramer JH, Rosen HJ, Boxer A, Miller BL, Green AJ, Elahi FM, …
Feasibility and considerations of epsin2 as a candidate target for multiple system atrophy treatment.
Expert opinion on therapeutic targets 2023 Cheng A, Cai B, Fukunaga K, Sasaki T, Lakkaraju A
Optineurin tunes outside-in signaling to regulate lysosome biogenesis and phagocytic clearance in the retina.
Current biology : CB 2023 Tan LX, Germer CJ, Thamban T, La Cunza N, Lakkaraju A

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Analysis of mitochondrial dynamics and function in the retinal pigment epithelium by high-speed high-resolution live imaging.
Frontiers in cell and developmental biology 2022 Tan LX, Li J, Germer CJ, Lakkaraju A
Does senescence play a role in age-related macular degeneration?
Experimental eye research 2022 Malek G, Campisi J, Kitazawa K, Webster C, Lakkaraju A, Skowronska-Krawczyk D
Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration.
Experimental eye research 2022 Bharti K, den Hollander AI, Lakkaraju A, Sinha D, Williams DS, Finnemann SC, Bowes-Rickman C, Malek G, D'Amore PA
Mitochondria-dependent phase separation of disease-relevant proteins drives pathological features of age-related macular degeneration.
JCI insight 2021 La Cunza N, Tan LX, Thamban T, Germer CJ, Rathnasamy G, Toops KA, Lakkaraju A
Endoplasmic reticulum acetyltransferases Atase1 and Atase2 differentially regulate reticulophagy, macroautophagy and cellular acetyl-CoA metabolism.
Communications biology 2021 Rigby MJ, Lawton AJ, Kaur G, Banduseela VC, Kamm WE, Lakkaraju A, Denu JM, Puglielli L
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
Autophagy 2021 Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A, Adamopoulos IE, Adeli K, Adolph TE, Adornetto A, Aflaki E, Agam G, …
Complement activation, lipid metabolism, and mitochondrial injury: Converging pathways in age-related macular degeneration.
Redox biology 2020 Tan LX, Germer CJ, La Cunza N, Lakkaraju A
The cell biology of the retinal pigment epithelium.
Progress in retinal and eye research 2020 Lakkaraju A, Umapathy A, Tan LX, Daniele L, Philp NJ, Boesze-Battaglia K, Williams DS
Centrosome Amplification in Cancer Disrupts Autophagy and Sensitizes to Autophagy Inhibition.
Molecular cancer research : MCR 2019 Denu RA, Kaur G, Sass MM, Lakkaraju A, Burkard ME
A NOVEL ROLE FOR THE FTD-CAUSING PROTEIN PROGRANULIN IN APOPTOSIS SIGNALING.
Alzheimer's & Dementia 2019 Claire Clelland, J. Iker Etchegaray, Lay Kodama, Faten Sayed, Aradhana Sachdev, Yaqiao Li, David Le, Lihong Zhan, Yungui Zhou, Duc Duong, Nicholas T. Seyfried, Thomas G. Kukar, Li Xuan Tan, Aparna …
“Use of Inhibitors of Acid Sphingomyelinase to Treat Acquired and Inherited Retinal Degenerations”
“Use of Inhibitors of Acid Sphingomyelinase to Treat Acquired and Inherited Retinal Degenerations”. 2018 Lakkaraju A, ToopsKA, Tan LX
Aberrant early endosome biogenesis mediates complement activation in the retinal pigment epithelium in models of macular degeneration.
Proceedings of the National Academy of Sciences of the United States of America 2018 Kaur G, Tan LX, Rathnasamy G, La Cunza N, Germer CJ, Toops KA, Fernandes M, Blenkinsop TA, Lakkaraju A
Early Endosome Morphology in Health and Disease.
Advances in experimental medicine and biology 2018 Kaur G, Lakkaraju A
Drusen Ooze: A Novel Hypothesis in Geographic Atrophy.
Ophthalmology. Retina 2017 Monés J, Garcia M, Biarnés M, Lakkaraju A, Ferraro L
Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells.
Molecular vision 2017 Samuel W, Jaworski C, Postnikova OA, Kutty RK, Duncan T, Tan LX, Poliakov E, Lakkaraju A, Redmond TM
Novel roles for the radial spoke head protein 9 in neural and neurosensory cilia.
Scientific reports 2016 Sedykh I, TeSlaa JJ, Tatarsky RL, Keller AN, Toops KA, Lakkaraju A, Nyholm MK, Wolman MA, Grinblat Y
Protective responses to sublytic complement in the retinal pigment epithelium.
Proceedings of the National Academy of Sciences of the United States of America 2016 Tan LX, Toops KA, Lakkaraju A
Apolipoprotein E Isoforms and AMD.
Advances in experimental medicine and biology 2016 Toops KA, Tan LX, Lakkaraju A
Cholesterol-mediated activation of acid sphingomyelinase disrupts autophagy in the retinal pigment epithelium.
Molecular biology of the cell 2014 Toops KA, Tan LX, Jiang Z, Radu RA, Lakkaraju A
A detailed three-step protocol for live imaging of intracellular traffic in polarized primary porcine RPE monolayers.
Experimental eye research 2014 Toops KA, Tan LX, Lakkaraju A
Multiple A2E treatments lead to melanization of rod outer segment-challenged ARPE-19 cells.
Molecular vision 2014 Poliakov E, Strunnikova NV, Jiang JK, Martinez B, Parikh T, Lakkaraju A, Thomas C, Brooks BP, Redmond TM
Should I stay or should I go? Trafficking of sub-lytic MAC in the retinal pigment epithelium.
Advances in experimental medicine and biology 2014 Lakkaraju A, Toops KA, Xu J
Mechanism of polarized lysosome exocytosis in epithelial cells.
Journal of Cell Science 2013 Jin Xu, Kimberly A. Toops, Fernando Diaz, Jose Maria Carvajal-Gonzalez, Diego Gravotta, Francesca Mazzoni, Ryan Schreiner, Enrique Rodriguez-Boulan, Aparna Lakkaraju
Let's play a game of chutes and ladders: Lysosome fusion with the epithelial plasma membrane.
Communicative & integrative biology 2013 Toops KA, Lakkaraju A
Mechanism of polarized lysosome exocytosis in epithelial cells.
Journal of cell science 2012 Xu J, Toops KA, Diaz F, Carvajal-Gonzalez JM, Gravotta D, Mazzoni F, Schreiner R, Rodriguez-Boulan E, Lakkaraju A
Endo-lysosome function in the retinal pigment epithelium in health and disease.
Advances in experimental medicine and biology 2012 Lakkaraju A
It takes two to tango to the melanosome.
The Journal of cell biology 2009 Lakkaraju A, Carvajal-Gonzalez JM, Rodriguez-Boulan E
Ultrasound for initial evaluation and triage of clinically suspicious soft-tissue masses.
Clinical radiology 2009 Lakkaraju A, Sinha R, Garikipati R, Edward S, Robinson P
In vivo diffusion of lactoferrin in brain extracellular space is regulated by interactions with heparan sulfate.
Proceedings of the National Academy of Sciences of the United States of America 2008 Thorne RG, Lakkaraju A, Rodriguez-Boulan E, Nicholson C
Itinerant exosomes: emerging roles in cell and tissue polarity.
Trends in cell biology 2008 Lakkaraju A, Rodriguez-Boulan E
Golgi apparatus and epithelial cell polarity.
The Golgi Apparatus 2008 Sylvie Deborde, Diego Gravotta, Aparna Lakkaraju, Enrique Rodriguez-Boulan
Cell biology: caught in the traffic.
Nature 2007 Lakkaraju A, Rodriguez-Boulan E
The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells.
Proceedings of the National Academy of Sciences of the United States of America 2007 Lakkaraju A, Finnemann SC, Rodriguez-Boulan E
Epithelial Cells.
Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine 2006 Aparna Lakkaraju, Enrique Rodriguez-Boulan
Evolving endosomes: how many varieties and why?
Current opinion in cell biology 2005 Perret E, Lakkaraju A, Deborde S, Schreiner R, Rodriguez-Boulan E
Low-density lipoprotein receptor-related protein mediates the endocytosis of anionic liposomes in neurons.
The Journal of biological chemistry 2002 Lakkaraju A, Rahman YE, Dubinsky JM
Neurons are protected from excitotoxic death by p53 antisense oligonucleotides delivered in anionic liposomes.
The Journal of biological chemistry 2001 Lakkaraju A, Dubinsky JM, Low WC, Rahman YE

Aparna Lakkaraju, PhDProfessorOphthalmologySchool of Medicine