Aparna Lakkaraju, PhD

Title(s)Professor, Ophthalmology
SchoolSchool of Medicine
Address1550 Fourth Street, #448F
San Francisco CA 94158
Phone415-502-9670
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    Collapse Biography 
    Collapse Education and Training
    University of Minnesota, MinneapolisPhDPharmaceutical Sciences
    Cornell University Weill Medical College, New YorkPost-doctoral TrainingOphthalmology & Cell Biology
    Collapse Awards and Honors
    Research to Prevent Blindness Foundation2019  - 2022Catalyst Award for Innovative Approaches to Age-Related Macular Degeneration
    BrightFocus Foundation2015  - 2018Charlotte & Alexander Danilevsky Award for Macular Degeneration Research
    Wisconsin Partnership Program2015  - 2017New Investigator Award
    Retina Research Foundation2012  - 2018Rebecca Meyer Brown Professorship
    Research to Prevent Blindness2010  - 2014Career Development Award
    National Eye Institute2003  - 2006Ruth L. Kirchstein F32 Individual Post-Doctoral Fellowship Award
    BrightFocus Foundation2021  - 2024Lorraine Maresca Innovative Research Award
    BrightFocus Foundation2021  - 2024Lorraine Maresca Innovative Research Award

    Collapse Overview 
    Collapse Overview
    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. 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).
    Collapse Websites
    Collapse Mentoring

    Collapse Research 
    Collapse Research Activities and Funding
    Mechanisms of RPE dysfunction in macular degenerations: role of intracellular complement activation
    NIH R01EY030668May 1, 2020 - Apr 30, 2025
    Role: Principal Investigator
    Novel Approaches to Identify Tipping Points and Therapeutic Targets for Early AMD
    Research to Prevent Blindness Catalyst AwardAug 1, 2019 - Jul 31, 2022
    Role: Principal Investigator
    Modulating Mitochondrial Dynamics in the Retinal Pigment Epithelium as a Therapeutic Strategy for Macular Dystrophies
    Macular Society UK Dec 1, 2015 - Jun 30, 2019
    Role: Principal Investigator
    Mechanisms of cellular clearance in the retinal pigment epithelium
    NIH R01EY023299Aug 1, 2015 - Jul 31, 2021
    Role: Principal Investigator
    Can RPE-derived Exosomes Contribute to Subretinal Drusenoid Deposits?
    BrightFocus Foundation M2015350Jul 1, 2015 - Jun 30, 2018
    Role: Principal Investigator
    Lysosome function and autophagy in age-related macular degeneration
    American Federation for Aging Research Jul 1, 2013 - Jun 30, 2015
    Role: Principal Investigator
    Role of Cholesterol Homeostasis in Macular Degeneration
    NIH F32EY015363Dec 1, 2003 - Nov 30, 2006
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    1. Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration. bioRxiv. 2024 Jun 14. Yu A, Tan LX, Lakkaraju A, Santina LD, Ou Y. PMID: 38915631; PMCID: PMC11195198.
      View in: PubMed   Mentions:
    2. Targeting complement C3a receptor resolves mitochondrial hyperfusion and subretinal microglial activation in progranulin-deficient frontotemporal dementia. bioRxiv. 2024 Jun 01. 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, Lakkaraju A. PMID: 38854134; PMCID: PMC11160746.
      View in: PubMed   Mentions:
    3. Feasibility and considerations of epsin2 as a candidate target for multiple system atrophy treatment. Expert Opin Ther Targets. 2023 Jul-Dec; 27(11):1031-1034. Cheng A, Cai B, Fukunaga K, Sasaki T, Lakkaraju A. PMID: 37902421.
      View in: PubMed   Mentions:    Fields:    Translation:Humans
    4. Optineurin tunes outside-in signaling to regulate lysosome biogenesis and phagocytic clearance in the retina. Curr Biol. 2023 09 25; 33(18):3805-3820.e7. Tan LX, Germer CJ, Thamban T, La Cunza N, Lakkaraju A. PMID: 37586372; PMCID: PMC10529777.
      View in: PubMed   Mentions: 3     Fields:    Translation:AnimalsCells
    5. Analysis of mitochondrial dynamics and function in the retinal pigment epithelium by high-speed high-resolution live imaging. Front Cell Dev Biol. 2022; 10:1044672. Tan LX, Li J, Germer CJ, Lakkaraju A. PMID: 36393836; PMCID: PMC9651161.
      View in: PubMed   Mentions: 5  
    6. Does senescence play a role in age-related macular degeneration? Exp Eye Res. 2022 12; 225:109254. Malek G, Campisi J, Kitazawa K, Webster C, Lakkaraju A, Skowronska-Krawczyk D. PMID: 36150544; PMCID: PMC10032649.
      View in: PubMed   Mentions: 4     Fields:    Translation:Humans
    7. Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration. Exp Eye Res. 2022 09; 222:109170. Bharti K, den Hollander AI, Lakkaraju A, Sinha D, Williams DS, Finnemann SC, Bowes-Rickman C, Malek G, D'Amore PA. PMID: 35835183; PMCID: PMC9444976.
      View in: PubMed   Mentions: 24     Fields:    Translation:HumansAnimalsCells
    8. Mitochondria-dependent phase separation of disease-relevant proteins drives pathological features of age-related macular degeneration. JCI Insight. 2021 05 10; 6(9). La Cunza N, Tan LX, Thamban T, Germer CJ, Rathnasamy G, Toops KA, Lakkaraju A. PMID: 33822768; PMCID: PMC8262309.
      View in: PubMed   Mentions: 15     Fields:    Translation:AnimalsCells
    9. Endoplasmic reticulum acetyltransferases Atase1 and Atase2 differentially regulate reticulophagy, macroautophagy and cellular acetyl-CoA metabolism. Commun Biol. 2021 04 12; 4(1):454. Rigby MJ, Lawton AJ, Kaur G, Banduseela VC, Kamm WE, Lakkaraju A, Denu JM, Puglielli L. PMID: 33846551; PMCID: PMC8041774.
      View in: PubMed   Mentions: 10  Translation:AnimalsCells
    10. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy. 2021 Jan; 17(1):1-382. 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, Agarwal A, Aggarwal BB, Agnello M, Agostinis P, Agrewala JN, Agrotis A, Aguilar PV, Ahmad ST, Ahmed ZM, Ahumada-Castro U, Aits S, Aizawa S, Akkoc Y, Akoumianaki T, Akpinar HA, Al-Abd AM, Al-Akra L, Al-Gharaibeh A, Alaoui-Jamali MA, Alberti S, Alcocer-Gómez E, Alessandri C, Ali M, Alim Al-Bari MA, Aliwaini S, Alizadeh J, Almacellas E, Almasan A, Alonso A, Alonso GD, Altan-Bonnet N, Altieri DC, Álvarez ÉMC, Alves S, Alves da Costa C, Alzaharna MM, Amadio M, Amantini C, Amaral C, Ambrosio S, Amer AO, Ammanathan V, An Z, Andersen SU, Andrabi SA, Andrade-Silva M, Andres AM, Angelini S, Ann D, Anozie UC, Ansari MY, Antas P, Antebi A, Antón Z, Anwar T, Apetoh L, Apostolova N, Araki T, Araki Y, Arasaki K, Araújo WL, Araya J, Arden C, Arévalo MA, Arguelles S, Arias E, Arikkath J, Arimoto H, Ariosa AR, Armstrong-James D, Arnauné-Pelloquin L, Aroca A, Arroyo DS, Arsov I, Artero R, Asaro DML, Aschner M, Ashrafizadeh M, Ashur-Fabian O, Atanasov AG, Au AK, Auberger P, Auner HW, Aurelian L, Autelli R, Avagliano L, Ávalos Y, Aveic S, Aveleira CA, Avin-Wittenberg T, Aydin Y, Ayton S, Ayyadevara S, Azzopardi M, Baba M, Backer JM, Backues SK, Bae DH, Bae ON, Bae SH, Baehrecke EH, Baek A, Baek SH, Baek SH, Bagetta G, Bagniewska-Zadworna A, Bai H, Bai J, Bai X, Bai Y, Bairagi N, Baksi S, Balbi T, Baldari CT, Balduini W, Ballabio A, Ballester M, Balazadeh S, Balzan R, Bandopadhyay R, Banerjee S, Banerjee S, Bánréti Á, Bao Y, Baptista MS, Baracca A, Barbati C, Bargiela A, Barilà D, Barlow PG, Barmada SJ, Barreiro E, Barreto GE, Bartek J, Bartel B, Bartolome A, Barve GR, Basagoudanavar SH, Bassham DC, Bast RC, Basu A, Batoko H, Batten I, Baulieu EE, Baumgarner BL, Bayry J, Beale R, Beau I, Beaumatin F, Bechara LRG, Beck GR, Beers MF, Begun J, Behrends C, Behrens GMN, Bei R, Bejarano E, Bel S, Behl C, Belaid A, Belgareh-Touzé N, Bellarosa C, Belleudi F, Belló Pérez M, Bello-Morales R, Beltran JSO, Beltran S, Benbrook DM, Bendorius M, Benitez BA, Benito-Cuesta I, Bensalem J, Berchtold MW, Berezowska S, Bergamaschi D, Bergami M, Bergmann A, Berliocchi L, Berlioz-Torrent C, Bernard A, Berthoux L, Besirli CG, Besteiro S, Betin VM, Beyaert R, Bezbradica JS, Bhaskar K, Bhatia-Kissova I, Bhattacharya R, Bhattacharya S, Bhattacharyya S, Bhuiyan MS, Bhutia SK, Bi L, Bi X, Biden TJ, Bijian K, Billes VA, Binart N, Bincoletto C, Birgisdottir AB, Bjorkoy G, Blanco G, Blas-Garcia A, Blasiak J, Blomgran R, Blomgren K, Blum JS, Boada-Romero E, Boban M, Boesze-Battaglia K, Boeuf P, Boland B, Bomont P, Bonaldo P, Bonam SR, Bonfili L, Bonifacino JS, Boone BA, Bootman MD, Bordi M, Borner C, Bornhauser BC, Borthakur G, Bosch J, Bose S, Botana LM, Botas J, Boulanger CM, Boulton ME, Bourdenx M, Bourgeois B, Bourke NM, Bousquet G, Boya P, Bozhkov PV, Bozi LHM, Bozkurt TO, Brackney DE, Brandts CH, Braun RJ, Braus GH, Bravo-Sagua R, Bravo-San Pedro JM, Brest P, Bringer MA, Briones-Herrera A, Broaddus VC, Brodersen P, Brodsky JL, Brody SL, Bronson PG, Bronstein JM, Brown CN, Brown RE, Brum PC, Brumell JH, Brunetti-Pierri N, Bruno D, Bryson-Richardson RJ, Bucci C, Buchrieser C, Bueno M, Buitrago-Molina LE, Buraschi S, Buch S, Buchan JR, Buckingham EM, Budak H, Budini M, Bultynck G, Burada F, Burgoyne JR, Burón MI, Bustos V, Büttner S, Butturini E, Byrd A, Cabas I, Cabrera-Benitez S, Cadwell K, Cai J, Cai L, Cai Q, Cairó M, Calbet JA, Caldwell GA, Caldwell KA, Call JA, Calvani R, Calvo AC, Calvo-Rubio Barrera M, Camara NO, Camonis JH, Camougrand N, Campanella M, Campbell EM, Campbell-Valois FX, Campello S, Campesi I, Campos JC, et al. PMID: 33634751; PMCID: PMC7996087.
      View in: PubMed   Mentions: 1041     Fields:    Translation:HumansAnimalsCells
    11. Complement activation, lipid metabolism, and mitochondrial injury: Converging pathways in age-related macular degeneration. Redox Biol. 2020 10; 37:101781. Tan LX, Germer CJ, La Cunza N, Lakkaraju A. PMID: 33162377; PMCID: PMC7767764.
      View in: PubMed   Mentions: 17     Fields:    Translation:HumansCells
    12. The cell biology of the retinal pigment epithelium. Prog Retin Eye Res. 2020 Feb 24; 100846. Lakkaraju A, Umapathy A, Tan LX, Daniele L, Philp NJ, Boesze-Battaglia K, Williams DS. PMID: 32105772; PMCID: PMC8941496.
      View in: PubMed   Mentions: 144     Fields:    
    13. Centrosome Amplification in Cancer Disrupts Autophagy and Sensitizes to Autophagy Inhibition. Mol Cancer Res. 2020 01; 18(1):33-45. Denu RA, Kaur G, Sass MM, Lakkaraju A, Burkard ME. PMID: 31604847; PMCID: PMC6942210.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansCells
    14. A NOVEL ROLE FOR THE FTD-CAUSING PROTEIN PROGRANULIN IN APOPTOSIS SIGNALING. Alzheimer's & Dementia. 2019 Jul 1; 15(7):p1509. Clelland CC, Etchegaray EJ, Kodama KL, Sayed SF, Sachdev SA, Li LY, Le LD, Zhan ZL, Zhou ZY, Duong DD, Seyfried SN, Kukar KT, Tan TL, Lakkaraju LA, Conklin CB, Gan GL. .
      View in: Publisher Site   Mentions:
    15. “Use of Inhibitors of Acid Sphingomyelinase to Treat Acquired and Inherited Retinal Degenerations”. 2018. Lakkaraju A, ToopsKA, Tan LX.
    16. Aberrant early endosome biogenesis mediates complement activation in the retinal pigment epithelium in models of macular degeneration. Proc Natl Acad Sci U S A. 2018 09 04; 115(36):9014-9019. Kaur G, Tan LX, Rathnasamy G, La Cunza N, Germer CJ, Toops KA, Fernandes M, Blenkinsop TA, Lakkaraju A. PMID: 30126999; PMCID: PMC6130344.
      View in: PubMed   Mentions: 48     Fields:    Translation:HumansAnimalsCells
    17. Early Endosome Morphology in Health and Disease. Adv Exp Med Biol. 2018; 1074:335-343. Kaur G, Lakkaraju A. PMID: 29721961; PMCID: PMC6563932.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansAnimalsCells
    18. Drusen Ooze: A Novel Hypothesis in Geographic Atrophy. Ophthalmol Retina. 2017 Nov - Dec; 1(6):461-473. Monés J, Garcia M, Biarnés M, Lakkaraju A, Ferraro L. PMID: 31047436.
      View in: PubMed   Mentions: 4     Fields:    
    19. Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells. Mol Vis. 2017; 23:60-89. Samuel W, Jaworski C, Postnikova OA, Kutty RK, Duncan T, Tan LX, Poliakov E, Lakkaraju A, Redmond TM. PMID: 28356702; PMCID: PMC5360456.
      View in: PubMed   Mentions: 84     Fields:    Translation:HumansCells
    20. Novel roles for the radial spoke head protein 9 in neural and neurosensory cilia. Sci Rep. 2016 Sep 30; 6:34437. Sedykh I, TeSlaa JJ, Tatarsky RL, Keller AN, Toops KA, Lakkaraju A, Nyholm MK, Wolman MA, Grinblat Y. PMID: 27687975; PMCID: PMC5043386.
      View in: PubMed   Mentions: 10     Fields:    
    21. Protective responses to sublytic complement in the retinal pigment epithelium. Proc Natl Acad Sci U S A. 2016 08 02; 113(31):8789-94. Tan LX, Toops KA, Lakkaraju A. PMID: 27432952; PMCID: PMC4978296.
      View in: PubMed   Mentions: 31     Fields:    Translation:HumansAnimalsCells
    22. Apolipoprotein E Isoforms and AMD. Adv Exp Med Biol. 2016; 854:3-9. Toops KA, Tan LX, Lakkaraju A. PMID: 26427386.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansCells
    23. Cholesterol-mediated activation of acid sphingomyelinase disrupts autophagy in the retinal pigment epithelium. Mol Biol Cell. 2015 Jan 01; 26(1):1-14. Toops KA, Tan LX, Jiang Z, Radu RA, Lakkaraju A. PMID: 25378587; PMCID: PMC4279221.
      View in: PubMed   Mentions: 58     Fields:    Translation:HumansAnimalsCells
    24. A detailed three-step protocol for live imaging of intracellular traffic in polarized primary porcine RPE monolayers. Exp Eye Res. 2014 Jul; 124:74-85. Toops KA, Tan LX, Lakkaraju A. PMID: 24861273; PMCID: PMC4100485.
      View in: PubMed   Mentions: 34     Fields:    Translation:AnimalsCells
    25. Multiple A2E treatments lead to melanization of rod outer segment-challenged ARPE-19 cells. Mol Vis. 2014; 20:285-300. Poliakov E, Strunnikova NV, Jiang JK, Martinez B, Parikh T, Lakkaraju A, Thomas C, Brooks BP, Redmond TM. PMID: 24644403; PMCID: PMC3955416.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansAnimalsCells
    26. Should I stay or should I go? Trafficking of sub-lytic MAC in the retinal pigment epithelium. Adv Exp Med Biol. 2014; 801:267-74. Lakkaraju A, Toops KA, Xu J. PMID: 24664707.
      View in: PubMed   Mentions: 10     Fields:    Translation:HumansCells
    27. Mechanism of polarized lysosome exocytosis in epithelial cells. Journal of Cell Science. 2013 Nov 1; 126(21):5086-5086. Xu XJ, Toops TK, Diaz DF, Carvajal-Gonzalez CJ, Gravotta GD, Mazzoni MF, Schreiner SR, Rodriguez-Boulan RE, Lakkaraju LA. .
      View in: Publisher Site   Mentions:
    28. Let's play a game of chutes and ladders: Lysosome fusion with the epithelial plasma membrane. Commun Integr Biol. 2013 Jul 01; 6(4):e24474. Toops KA, Lakkaraju A. PMID: 23986802; PMCID: PMC3742055.
      View in: PubMed   Mentions: 5  
    29. Mechanism of polarized lysosome exocytosis in epithelial cells. J Cell Sci. 2012 Dec 15; 125(Pt 24):5937-43. Xu J, Toops KA, Diaz F, Carvajal-Gonzalez JM, Gravotta D, Mazzoni F, Schreiner R, Rodriguez-Boulan E, Lakkaraju A. PMID: 23038769; PMCID: PMC3585513.
      View in: PubMed   Mentions: 28     Fields:    Translation:AnimalsCells
    30. Endo-lysosome function in the retinal pigment epithelium in health and disease. Adv Exp Med Biol. 2012; 723:723-9. Lakkaraju A. PMID: 22183399.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansCells
    31. It takes two to tango to the melanosome. J Cell Biol. 2009 Oct 19; 187(2):161-3. Lakkaraju A, Carvajal-Gonzalez JM, Rodriguez-Boulan E. PMID: 19841135; PMCID: PMC2768836.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansAnimalsCells
    32. Ultrasound for initial evaluation and triage of clinically suspicious soft-tissue masses. Clin Radiol. 2009 Jun; 64(6):615-21. Lakkaraju A, Sinha R, Garikipati R, Edward S, Robinson P. PMID: 19414084.
      View in: PubMed   Mentions: 28     Fields:    Translation:Humans
    33. In vivo diffusion of lactoferrin in brain extracellular space is regulated by interactions with heparan sulfate. Proc Natl Acad Sci U S A. 2008 Jun 17; 105(24):8416-21. Thorne RG, Lakkaraju A, Rodriguez-Boulan E, Nicholson C. PMID: 18541909; PMCID: PMC2448851.
      View in: PubMed   Mentions: 51     Fields:    Translation:HumansAnimalsCells
    34. Itinerant exosomes: emerging roles in cell and tissue polarity. Trends Cell Biol. 2008 May; 18(5):199-209. Lakkaraju A, Rodriguez-Boulan E. PMID: 18396047; PMCID: PMC3754907.
      View in: PubMed   Mentions: 186     Fields:    Translation:HumansAnimalsCells
    35. Golgi apparatus and epithelial cell polarity. The Golgi Apparatus. 2008 Jan 1; 563-579. Deborde DS, Gravotta GD, Lakkaraju LA, Rodriguez-Boulan RE. .
      View in: Publisher Site   Mentions:
    36. Cell biology: caught in the traffic. Nature. 2007 Jul 19; 448(7151):266-7. Lakkaraju A, Rodriguez-Boulan E. PMID: 17637651.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansAnimalsCells
    37. The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells. Proc Natl Acad Sci U S A. 2007 Jun 26; 104(26):11026-31. Lakkaraju A, Finnemann SC, Rodriguez-Boulan E. PMID: 17578916; PMCID: PMC1904145.
      View in: PubMed   Mentions: 87     Fields:    Translation:HumansCells
    38. Epithelial Cells. Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine. 2006 Jan 1; 516-523. Lakkaraju LA, Rodriguez-Boulan RE. .
      View in: Publisher Site   Mentions:
    39. Evolving endosomes: how many varieties and why? Curr Opin Cell Biol. 2005 Aug; 17(4):423-34. Perret E, Lakkaraju A, Deborde S, Schreiner R, Rodriguez-Boulan E. PMID: 15975780.
      View in: PubMed   Mentions: 57     Fields:    Translation:AnimalsCells
    40. Low-density lipoprotein receptor-related protein mediates the endocytosis of anionic liposomes in neurons. J Biol Chem. 2002 Apr 26; 277(17):15085-92. Lakkaraju A, Rahman YE, Dubinsky JM. PMID: 11830589.
      View in: PubMed   Mentions: 5     Fields:    Translation:AnimalsCells
    41. Neurons are protected from excitotoxic death by p53 antisense oligonucleotides delivered in anionic liposomes. J Biol Chem. 2001 Aug 24; 276(34):32000-7. Lakkaraju A, Dubinsky JM, Low WC, Rahman YE. PMID: 11406618.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimalsCells
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