Curriculum Vitae

Viviana Gradinaru

Professor of Neuroscience and Biological Engineering

California Institute of Technology

Pasadena, CA 91125

viviana@caltech.edu

Education and Training

2005-2010

PhD, Stanford University, Neuroscience, Mentor: Dr. Karl Deisseroth

2002-2005

BS, California Institute of Technology, Biology, Mentor: Dr. Paul H. Patterson

2000-2002

BS Candidate, University of Bucharest, Romania, Physics

Professional Appointments

2019-present

Co-Founder and BoD member, Capsida Biotherapeutics, Inc., Thousand Oaks, CA

2018-present

Professor of Neuroscience and Biological Engineering, Caltech, Pasadena, CA

2016-present

Director of the Molecular and Cellular Neuroscience Center, Chen Institute, Caltech, Pasadena, CA

2015-2021

Investigator, Heritage Medical Research Institute

2012-present

Faculty Director and PI, CLOVER (CLARITY, Optogenetics, and Vector Engineering Research) Center, Beckman Institute, Caltech

2012-2018

Assistant Professor, Biology and Biological Engineering, Caltech, Pasadena, CA

2011-2012

Co-Founder and Chief Technology Officer, Circuit Therapeutics (now MapLight, CA)

2010-2011

Research Associate, Psychiatry and CNC (Cracking Neural Code), Stanford University, Stanford, CA

Honors and Awards

2021

Fellow of the American Association for the Advancement of Science (AAAS)

For “extraordinary achievements in bioengineering and neuroscience, including development and sharing of multiple novel tools to enable functional and anatomical access to the vertebrate nervous system.”

2021

Max Planck Sabbatical Award, Germany (delayed to 2022 due to COVID)

2021

Leverhulme Visiting Professorship, UCL, UK

2021

Blavatnik National Awards for Young Scientists – Life Sciences Finalist

2020

Society for Neuroscience Young Investigator Award

2020

Science Magazine & PINS Prize for Neuromodulation Winner, essay in Science

2020

Blavatnik National Awards for Young Scientists – Life Sciences Finalist

2020

Outstanding New Investigator Award, American Society of Gene and Cell Therapy

2020

Addgene BLUE Flame Award

2019

Vilcek Prize for Creative Promise in Biomedical Science

2019

Blavatnik National Awards for Young Scientists – Life Sciences Finalist

2018

NIH Pioneer Award

2018

Gill Center Transformative Investigator Award

2017

Vallee Scholar

2017

Moore Inventor Fellow

2017

Innovators in Science Award, Early-Career Scientist in Neuroscience, Takeda and New York Academy of Sciences

2017

Eppendorf and Science Prize Finalist – essay published in Science

2016

Presidential Early Career Award for Scientists and Engineers (PECASE)

2016

Inaugural Peter Gruss Young Investigator Award, given biannually by Max Planck Florida

2015

Sloan Research Fellow

2015

Heritage Principal Investigator

2014

Cell 40 under 40

2013-2017

Pew Scholar Award

2013-2018

NIH Director’s New Innovator Award

2013

World Economic Forum Young Scientist

2013

TEDxCaltech: The Brain on “Brain Control with Light – Development and Application”

2013-2015

Kimmel Scholar Award for Cancer Research

2013-2016

Human Frontier Science Program (HFSP) Young Investigator Grant

2012

Watson Lecture “Brain Control with Light” Biedebach Memorial Lecture, Caltech

Scientific Leadership & Service

2021

Co-chair for the NIH BRAIN Initiative workshop on Circuit Therapies

2021

Member of Viral Gene Transfer Vectors Committee of the American Society of Gene and Cell Therapy

2020

Invited to join Allen Institute Scientific Advisory Board for MindScope Scientific Advisory Council

2020-present

Editorial Board Member Neuron, Cell Press

2019

NAS Proceedings Reviewer for “Advancing Gene-Targeted Therapies for Central Nervous System Disorders: Proceedings of a Workshop” for the Health and Medicine Division of the National Academies of Sciences, Engineering, and Medicine

2019

Session Co-Chair NIH/NINDS Workshop Session on “Improving Delivery and Distribution” during “Next Generation Strategies for Gene-Targeted Therapies of Central Nervous System Disorders”

2019

Scientific Co-Organizer “Engineering and Evolving Viruses to Expand Functionality” HHMI-Janelia Research Conference

2018-present

Co-organizer NSF NeuroNex MINT Workshop at U. Michigan

2018-present

Editorial Board Member, BMC Biology

2014-2017

Allen Brain Institute Council Member, Next Generation Leaders

2008-2017

Instructor, Cold Spring Harbor Laboratory, “Advanced Techniques in Molecular Neuroscience, Optogenetics and CLARITY Module”

2016

NIH BRAIN Initiative Study Section for “Development and Validation of Novel Tools”

2015

SFN, Chicago, Organizer and Co-Chair for Tissue Clearing Minisymposium

2015

NIH Molecular Neurogenetics (MNG) Study Section, ad hoc member

2012-present

Peer reviewer: Nature/Nat.Medicine/Neuro/Biotech/Protocols; PNAS, Neuron, Science

2010-present

Grant reviewer: NIH (BRAIN, MNG, DP2); MJFF; Wellcome Trust; Dystonia MRF; IWT Basic Research Belgium

Publications

  1. Abdel-Haq R, Schlachetzki JCM, Boktor JC, Cantu-Jungles TM, Thron T, Zhang M, Bostick JW, Khazaei T, Chilakala S, Morais LH, Humphrey G, Keshavarzian A, Katz JE, Thomson M, Knight R, Gradinaru V, Hamaker BR, Glass CK, Mazmanian SK. A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice. eLife. 2022 Nov 8;11e81453. doi: 10.7554/eLife.81453. PMID: 36346385
  2. Endo F, Kasai A, Soto JS, Yu X, Qu Z, Hashimoto H, Gradinaru V, Kawaguchi R, Khakh BS. Molecular basis of astroctye diversity and morphology across the CNS in health and disease. Science. 2022 Nov 4;378(6619):eadc9020. doi: 10.1126/science.adc9020. PMID: 36378959.
  3. Goertsen D, Goeden N, Flytzanis NC, Gradinaru V. Targeting the lung epithelium after intravenous delivery by directed evolution of underexplored sites on the AAV capsid. Mol Ther Methods Clin Dev. 2022 Sep 8;26:331-342. doi: 10.1016/j.omtm.2022.07.010. PMID: 35990749; PMCID: PMC9372736.
  4. Jang S, Shen HK, Ding X, Miles TF, Gradinaru V. Structural basis of receptor usage by the engineered capsid AAV-PHP.eB. Mol Ther Methods Clin Dev. 2022 Sep 8;26:343-354. doi: 10.1016/j.omtm.2022.07.011. PMID: 36034770; PMCID: PMC9382559.
  5. Seo JW, Ajenjo J, Wu B, Robinson E, Raie MN, Wang J, Tumbale SK, Buccino P, Anders DA, Shen B, Habte FG, Beinat C, James ML, Reyes ST, Ravindra Kumar S, Miles TF, Lee JT, Gradinaru V, Ferrara KW. Multimodal imaging of capsid and cargo reveals differential brain targeting and liver detargeting of systemically-administered AAVs. Biomaterials. 2022 Aug 6:121701. doi: 10.1016/j.biomaterials.2022.121701. PMID: 35985893; PMCID: PMC9621732.
  6. Chen X, Ravindra Kumar S, Adams CD, Yang D, Wang T, Wolfe DA, Arokiaraj CM, Ngo V, Campos LJ, Griffiths JA, Ichiki T, Mazmanian SK, Osborne PB, Keast JR, Miller CT, Fox AS, Chiu IM, Gradinaru V. Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems. Neuron. 2022 May 23:S0896-6273(22)00411-1. doi: 10.1016/j.neuron.2022.05.003. PMID: 35643078.
  7. Challis RC, Ravindra Kumar S, Chen X, Goertsen D, Coughlin GM, Hori AM, Chuapoco MR, Otis TS, Miles TF, Gradinaru V. Adeno-Associated Virus Toolkit to Target Diverse Brain Cells. Annu Rev Neurosci. 2022 Apr 19. doi: 10.1146/annurev-neuro-111020-100834. PMID: 35440143. 
  8. Cui L, Guo J, Cranfill SL, Gautam M, Bhattarai J, Olson W, Beattie K, Challis RC, Wu Q, Song X, Raabe T, Gradinaru V, Ma M, Liu Q, Luo W. Glutamate in primary afferents is required for itch transmission. Neuron. 2022 Mar 2;110(5):809-823.e5. doi: 10.1016/j.neuron.2021.12.007. Epub 2022 Jan 4. PMID: 34986325; PMCID: PMC8898340. 
  9. Goertsen D, Flytzanis NC, Goeden N, Chuapoco MR, Cummins A, Chen Y, Fan Y, Zhang Q, Sharma J, Duan Y, Wang L, Feng G, Chen Y, Ip NY, Pickel J, Gradinaru V. AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset. Nat Neurosci. 2022 Jan;25(1):106-115. doi: 10.1038/s41593-021-00969-4. PMID: 34887588. 
  10. Brown D, Altermatt M, Dobreva T, Chen S, Wang A, Thomson M, Gradinaru V. Deep Parallel Characterization of AAV Tropism and AAV-Mediated Transcriptional Changes <i>via</i> Single-Cell RNA Sequencing. Front Immunol. 2021 Oct 21;12:730825. doi: 10.3389/fimmu.2021.730825. PMID: 34759919; PMCID: PMC8574206. 
  11. Kahan A, Greenbaum A, Jang MJ, Robinson JE, Cho JR, Chen X, Kassraian P, Wagenaar DA, Gradinaru V. Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses. Cell Rep. 2021 Sep 28;36(13):109744. doi: 10.1016/j.celrep.2021.109744. PMID: 34592157; PMCID: PMC8552649. 
  12. Zhu M, Shahbazi M, Martin A, Zhang C, Sozen B, Borsos M, Mandelbaum RS, Paulson RJ, Mole MA, Esbert M, Titus S, Scott RT, Campbell A, Fishel S, Gradinaru V, Zhao H, Wu K, Chen ZJ, Seli E, de Los Santos MJ, Zernicka Goetz M. Human embryo polarization requires PLC signaling to mediate trophectoderm specification. Elife. 2021 Sep 27;10:e65068. doi: 10.7554/eLife.65068. PMID: 34569938; PMCID: PMC8514238. 
  13. Davidson CD, Gibson AL, Gu T, Baxter LL, Deverman BE, Beadle K, Incao AA, Rodriguez-Gil JL, Fujiwara H, Jiang X, Chandler RJ, Ory DS, Gradinaru V, Venditti CP, Pavan WJ. Improved systemic AAV gene therapy with a neurotrophic capsid in Niemann-Pick disease type C1 mice. Life Sci Alliance. 2021 Aug 18;4(10):e202101040. doi: 10.26508/lsa.202101040. PMID: 34407999; PMCID: PMC8380657. 
  14. Duan Y, Ye T, Qu Z, Chen Y, Miranda A, Zhou X, Lok KC, Chen Y, Fu AKY, Gradinaru V, Ip NY. Brain-wide Cas9-mediated cleavage of a gene causing familial Alzheimer’s disease alleviates amyloid-related pathologies in mice. Nat Biomed Eng. 2022 Feb;6(2):168-180. doi: 10.1038/s41551-021-00759-0. Epub 2021 Jul 26. PMID: 34312508. 
  15. Fan JP, Geng HZ, Ji YW, Jia T, Treweek JB, Li AA, Zhou CY, Gradinaru V, Xiao C. Age-dependent alterations in key components of the nigrostriatal dopaminergic system and distinct motor phenotypes. Acta Pharmacol Sin. 2022 Apr;43(4):862-875. doi: 10.1038/s41401-021-00713-5. Epub 2021 Jul 9. PMID: 34244603; PMCID: PMC8975991. 
  16. Wu WL, Adame MD, Liou CW, Barlow JT, Lai TT, Sharon G, Schretter CE, Needham BD, Wang MI, Tang W, Ousey J, Lin YY, Yao TH, Abdel-Haq R, Beadle K, Gradinaru V, Ismagilov RF, Mazmanian SK. Microbiota regulate social behaviour via stress response neurons in the brain. Nature. 2021 Jul;595(7867):409-414. doi: 10.1038/s41586-021-03669-y. Epub 2021 Jun 30. PMID: 34194038; PMCID: PMC8346519. 
  17. Nagai J, Bellafard A, Qu Z, Yu X, Ollivier M, Gangwani MR, Diaz-Castro B, Coppola G, Schumacher SM, Golshani P, Gradinaru V, Khakh BS. Specific and behaviorally consequential astrocyte G<sub>q</sub> GPCR signaling attenuation in vivo with iβARK. Neuron. 2021 Jul 21;109(14):2256-2274.e9. doi: 10.1016/j.neuron.2021.05.023. Epub 2021 Jun 16. PMID: 34139149; PMCID: PMC8418870. 
  18. Smith EJ, Farshim PP, Flomen R, Jones ST, McAteer SJ, Deverman BE, Gradinaru V, Bates GP. Use of high-content imaging to quantify transduction of AAV-PHP viruses in the brain following systemic delivery. Brain Commun. 2021 May 17;3(2):fcab105. doi: 10.1093/braincomms/fcab105. PMID: 34131644; PMCID: PMC8200048. 
  19. Smith SN, Schubert R, Simic B, Brücher D, Schmid M, Kirk N, Freitag PC, Gradinaru V, Plückthun A. The SHREAD gene therapy platform for paracrine delivery improves tumor localization and intratumoral effects of a clinical antibody. Proc Natl Acad Sci U S A. 2021 May 25;118(21):e2017925118. doi: 10.1073/pnas.2017925118. PMID: 34001602; PMCID: PMC8166199. 
  20. Helseth AR, Hernandez-Martinez R, Hall VL, Oliver ML, Turner BD, Caffall ZF, Rittiner JE, Shipman MK, King CS, Gradinaru V, Gerfen C, Costa-Mattioli M, Calakos N. Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice. Science. 2021 Apr 23;372(6540):eabe1931. doi: 10.1126/science.abe1931. PMID: 33888613; PMCID: PMC8457366.
  21. Mich JK, Graybuck LT, Hess EE, Mahoney JT, Kojima Y, Ding Y, Somasundaram S, Miller JA, Kalmbach BE, Radaelli C, Gore BB, Weed N, Omstead V, Bishaw Y, Shapovalova NV, Martinez RA, Fong O, Yao S, Mortrud M, Chong P, Loftus L, Bertagnolli D, Goldy J, Casper T, Dee N, Opitz-Araya X, Cetin A, Smith KA, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Keene CD, Silbergeld DL, Sunkin SM, Gradinaru V, Horwitz GD, Zeng H, Tasic B, Lein ES, Ting JT, Levi BP. Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex. Cell Rep. 2021 Mar 30;34(13):108754. doi: 10.1016/j.celrep.2021.108754. PMID: 33789096; PMCID: PMC8163032. 
  22. Graybuck LT, Daigle TL, Sedeño-Cortés AE, Walker M, Kalmbach B, Lenz GH, Morin E, Nguyen TN, Garren E, Bendrick JL, Kim TK, Zhou T, Mortrud M, Yao S, Siverts LA, Larsen R, Gore BB, Szelenyi ER, Trader C, Balaram P, van Velthoven CTJ, Chiang M, Mich JK, Dee N, Goldy J, Cetin AH, Smith K, Way SW, Esposito L, Yao Z, Gradinaru V, Sunkin SM, Lein E, Levi BP, Ting JT, Zeng H, Tasic B. Enhancer viruses for combinatorial cell-subclass-specific labeling. Neuron. 2021 May 5;109(9):1449-1464.e13. doi: 10.1016/j.neuron.2021.03.011. Epub 2021 Mar 30. PMID: 33789083; PMCID: PMC8610077. 
  23. Cho JR, Chen X, Kahan A, Robinson JE, Wagenaar DA, Gradinaru V. Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context. J Neurosci. 2021 Mar 24;41(12):2645-2655. doi: 10.1523/JNEUROSCI.2690-20.2021. Epub 2021 Feb 9. PMID: 33563725; PMCID: PMC8018733. 
  24. Unger EK, Keller JP, Altermatt M, Liang R, Matsui A, Dong C, Hon OJ, Yao Z, Sun J, Banala S, Flanigan ME, Jaffe DA, Hartanto S, Carlen J, Mizuno GO, Borden PM, Shivange AV, Cameron LP, Sinning S, Underhill SM, Olson DE, Amara SG, Temple Lang D, Rudnick G, Marvin JS, Lavis LD, Lester HA, Alvarez VA, Fisher AJ, Prescher JA, Kash TL, Yarov-Yarovoy V, Gradinaru V, Looger LL, Tian L. Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning. Cell. 2020 Dec 23;183(7):1986-2002.e26. doi: 10.1016/j.cell.2020.11.040. Epub 2020 Dec 16. PMID: 33333022; PMCID: PMC8025677. 
  25. Badimon A, Strasburger HJ, Ayata P, Chen X, Nair A, Ikegami A, Hwang P, Chan AT, Graves SM, Uweru JO, Ledderose C, Kutlu MG, Wheeler MA, Kahan A, Ishikawa M, Wang YC, Loh YE, Jiang JX, Surmeier DJ, Robson SC, Junger WG, Sebra R, Calipari ES, Kenny PJ, Eyo UB, Colonna M, Quintana FJ, Wake H, Gradinaru V, Schaefer A. Negative feedback control of neuronal activity by microglia. Nature. 2020 Oct;586(7829):417-423. doi: 10.1038/s41586-020-2777-8. Epub 2020 Sep 30. PMID: 32999463; PMCID: PMC7577179. 
  26. Gradinaru V. Expanding the brain researcher’s toolkit. Science. 2020 Aug 7;369(6504):637. doi: 10.1126/science.abd2660. PMID: 32764063. 
  27. Seo JW, Ingham ES, Mahakian L, Tumbale S, Wu B, Aghevlian S, Shams S, Baikoghli M, Jain P, Ding X, Goeden N, Dobreva T, Flytzanis NC, Chavez M, Singhal K, Leib R, James ML, Segal DJ, Cheng RH, Silva EA, Gradinaru V, Ferrara KW. Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation. Nat Commun. 2020 Apr 30;11(1):2102. doi: 10.1038/s41467-020-15818-4. PMID: 32355221; PMCID: PMC7193641. 
  28. Ravindra Kumar S, Miles TF, Chen X, Brown D, Dobreva T, Huang Q, Ding X, Luo Y, Einarsson PH, Greenbaum A, Jang MJ, Deverman BE, Gradinaru V. Multiplexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types. Nat Methods. 2020 May;17(5):541-550. doi: 10.1038/s41592-020-0799-7. Epub 2020 Apr 20. PMID: 32313222; PMCID: PMC7219404. 
  29. Rauch JN, Luna G, Guzman E, Audouard M, Challis C, Sibih YE, Leshuk C, Hernandez I, Wegmann S, Hyman BT, Gradinaru V, Kampmann M, Kosik KS. LRP1 is a master regulator of tau uptake and spread. Nature. 2020 Apr;580(7803):381-385. doi: 10.1038/s41586-020-2156-5. Epub 2020 Apr 1. PMID: 32296178; PMCID: PMC7687380. 
  30. Challis C, Hori A, Sampson TR, Yoo BB, Challis RC, Hamilton AM, Mazmanian SK, Volpicelli-Daley LA, Gradinaru V. Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice. Nat Neurosci. 2020 Mar;23(3):327-336. doi: 10.1038/s41593-020-0589-7. Epub 2020 Feb 17. PMID: 32066981; PMCID: PMC7065967. 
  31. Sampson TR, Challis C, Jain N, Moiseyenko A, Ladinsky MS, Shastri GG, Thron T, Needham BD, Horvath I, Debelius JW, Janssen S, Knight R, Wittung-Stafshede P, Gradinaru V, Chapman M, Mazmanian SK. A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice. Elife. 2020 Feb 11;9:e53111. doi: 10.7554/eLife.53111. PMID: 32043464; PMCID: PMC7012599. 
  32. Ueda HR, Ertürk A, Chung K, Gradinaru V, Chédotal A, Tomancak P, Keller PJ. Tissue clearing and its applications in neuroscience. Nat Rev Neurosci. 2020 Feb;21(2):61-79. doi: 10.1038/s41583-019-0250-1. PMID: 31896771; PMCID: PMC8121164. 
  33. Patriarchi T, Cho JR, Merten K, Marley A, Broussard GJ, Liang R, Williams J, Nimmerjahn A, von Zastrow M, Gradinaru V, Tian L. Imaging neuromodulators with high spatiotemporal resolution using genetically encoded indicators. Nat Protoc. 2019 Dec;14(12):3471-3505. doi: 10.1038/s41596-019-0239-2. Epub 2019 Nov 15. PMID: 31732722. 
  34. Bedbrook CN, Yang KK, Robinson JE, Mackey ED, Gradinaru V, Arnold FH. Machine learning-guided channelrhodopsin engineering enables minimally invasive optogenetics. Nat Methods. 2019 Nov;16(11):1176-1184. doi: 10.1038/s41592-019-0583-8. Epub 2019 Oct 14. PMID: 31611694; PMCID: PMC6858556. 
  35. Song A, Dai W, Jang MJ, Medrano L, Li Z, Zhao H, Shao M, Tan J, Li A, Ning T, Miller MM, Armstrong B, Huss JM, Zhu Y, Liu Y, Gradinaru V, Wu X, Jiang L, Scherer PE, Wang QA. Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue. J Clin Invest. 2020 Jan 2;130(1):247-257. doi: 10.1172/JCI129167. PMID: 31573981; PMCID: PMC6934193. 
  36. Ramirez-Zamora A, Giordano J, Boyden ES, Gradinaru V, Gunduz A, Starr PA, Sheth SA, McIntyre CC, Fox MD, Vitek J, Vedam-Mai V, Akbar U, Almeida L, Bronte- Stewart HM, Mayberg HS, Pouratian N, Gittis AH, Singer AC, Creed MC, Lazaro- Munoz G, Richardson M, Rossi MA, Cendejas-Zaragoza L, D’Haese PF, Chiong W, Gilron R, Chizeck H, Ko A, Baker KB, Wagenaar J, Harel N, Deeb W, Foote KD, Okun MS. Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics. Front Neurosci. 2019 Sep 12;13:936. doi: 10.3389/fnins.2019.00936. PMID: 31572109; PMCID: PMC6751331. 
  37. Robinson JE, Coughlin GM, Hori AM, Cho JR, Mackey ED, Turan Z, Patriarchi T, Tian L, Gradinaru V. Optical dopamine monitoring with dLight1 reveals mesolimbic phenotypes in a mouse model of neurofibromatosis type 1. Elife. 2019 Sep 23;8:e48983. doi: 10.7554/eLife.48983. PMID: 31545171; PMCID: PMC6819083. 
  38. Oikonomou G, Altermatt M, Zhang RW, Coughlin GM, Montz C, Gradinaru V, Prober DA. The Serotonergic Raphe Promote Sleep in Zebrafish and Mice. Neuron. 2019 Aug 21;103(4):686-701.e8. doi: 10.1016/j.neuron.2019.05.038. Epub 2019 Jun 24. PMID: 31248729; PMCID: PMC6706304. 
  39. Rajendran PS, Challis RC, Fowlkes CC, Hanna P, Tompkins JD, Jordan MC, Hiyari S, Gabris-Weber BA, Greenbaum A, Chan KY, Deverman BE, Münzberg H, Ardell JL, Salama G, Gradinaru V, Shivkumar K. Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies. Nat Commun. 2019 Apr 26;10(1):1944. doi: 10.1038/s41467-019-09770-1. PMID: 31028266; PMCID: PMC6486614. 
  40. Zeng J, Wang Y, Luo Z, Chang LC, Yoo JS, Yan H, Choi Y, Xie X, Deverman BE, Gradinaru V, Gupton SL, Zlokovic BV, Zhao Z, Jung JU. TRIM9-Mediated Resolution of Neuroinflammation Confers Neuroprotection upon Ischemic Stroke in Mice. Cell Rep. 2019 Apr 9;27(2):549-560.e6. doi: 10.1016/j.celrep.2018.12.055. PMID: 30970257; PMCID: PMC6485958. 
  41. Challis RC, Ravindra Kumar S, Chan KY, Challis C, Beadle K, Jang MJ, Kim HM, Rajendran PS, Tompkins JD, Shivkumar K, Deverman BE, Gradinaru V. Systemic AAV vectors for widespread and targeted gene delivery in rodents. Nat Protoc. 2019 Feb;14(2):379-414. doi: 10.1038/s41596-018-0097-3. PMID: 30626963. 
  42. Mano T, Albanese A, Dodt HU, Erturk A, Gradinaru V, Treweek JB, Miyawaki A, Chung K, Ueda HR. Whole-Brain Analysis of Cells and Circuits by Tissue Clearing and Light-Sheet Microscopy. J Neurosci. 2018 Oct 31;38(44):9330-9337. doi: 10.1523/JNEUROSCI.1677-18.2018. PMID: 30381424; PMCID: PMC6706004. 
  43. Arbabi E, Li J, Hutchins RJ, Kamali SM, Arbabi A, Horie Y, Van Dorpe P, Gradinaru V, Wagenaar DA, Faraon A. Two-Photon Microscopy with a Double- Wavelength Metasurface Objective Lens. Nano Lett. 2018 Aug 8;18(8):4943-4948. doi: 10.1021/acs.nanolett.8b01737. Epub 2018 Jul 23. PMID: 30016110. 
  44. Patriarchi T, Cho JR, Merten K, Howe MW, Marley A, Xiong WH, Folk RW, Broussard GJ, Liang R, Jang MJ, Zhong H, Dombeck D, von Zastrow M, Nimmerjahn A, Gradinaru V, Williams JT, Tian L. Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science. 2018 Jun 29;360(6396):eaat4422. doi: 10.1126/science.aat4422. Epub 2018 May 31. PMID: 29853555; PMCID: PMC6287765. 
  45. Gradinaru V, Treweek J, Overton K, Deisseroth K. Hydrogel-Tissue Chemistry: Principles and Applications. Annu Rev Biophys. 2018 May 20;47:355-376. doi: 10.1146/annurev-biophys-070317-032905. PMID: 29792820; PMCID: PMC6359929. 
  46. Zelikowsky M, Hui M, Karigo T, Choe A, Yang B, Blanco MR, Beadle K, Gradinaru V, Deverman BE, Anderson DJ. The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress. Cell. 2018 May 17;173(5):1265-1279.e19. doi: 10.1016/j.cell.2018.03.037. PMID: 29775595; PMCID: PMC5967263. 
  47. Bedbrook CN, Deverman BE, Gradinaru V. Viral Strategies for Targeting the Central and Peripheral Nervous Systems. Annu Rev Neurosci. 2018 Jul 8;41:323-348. doi: 10.1146/annurev-neuro-080317-062048. Epub 2018 Apr 25. PMID: 29709207. 
  48. Ruan H, Brake J, Robinson JE, Liu Y, Jang M, Xiao C, Zhou C, Gradinaru V, Yang C. Deep tissue optical focusing and optogenetic modulation with time- reversed ultrasonically encoded light. Sci Adv. 2017 Dec 8;3(12):eaao5520. doi: 10.1126/sciadv.aao5520. PMID: 29226248; PMCID: PMC5722648. 
  49. Gradinaru V. Overriding sleep. Science. 2017 Oct 27;358(6362):457. doi: 10.1126/science.aap9535. PMID: 29074759. 
  50. Bedbrook CN, Yang KK, Rice AJ, Gradinaru V, Arnold FH. Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization. PLoS Comput Biol. 2017 Oct 23;13(10):e1005786. doi: 10.1371/journal.pcbi.1005786. PMID: 29059183; PMCID: PMC5695628. 
  51. Greenbaum A, Jang MJ, Challis C, Gradinaru V. Q&A: How can advances in tissue clearing and optogenetics contribute to our understanding of normal and diseased biology? BMC Biol. 2017 Sep 25;15(1):87. doi: 10.1186/s12915-017-0421-3. PMID: 28946882; PMCID: PMC5613628. 
  52. Nath RD, Bedbrook CN, Abrams MJ, Basinger T, Bois JS, Prober DA, Sternberg PW, Gradinaru V, Goentoro L. The Jellyfish Cassiopea Exhibits a Sleep-like State. Curr Biol. 2017 Oct 9;27(19):2984-2990.e3. doi: 10.1016/j.cub.2017.08.014. Epub 2017 Sep 21. PMID: 28943083; PMCID: PMC5653286. 
  53. Robinson JE, Gradinaru V. Dopaminergic dysfunction in neurodevelopmental disorders: recent advances and synergistic technologies to aid basic research. Curr Opin Neurobiol. 2018 Feb;48:17-29. doi: 10.1016/j.conb.2017.08.003. Epub 2017 Aug 30. PMID: 28850815; PMCID: PMC5825239. 
  54. Chan KY, Jang MJ, Yoo BB, Greenbaum A, Ravi N, Wu WL, Sánchez-Guardado L, Lois C, Mazmanian SK, Deverman BE, Gradinaru V. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat Neurosci. 2017 Aug;20(8):1172-1179. doi: 10.1038/nn.4593. Epub 2017 Jun 26. PMID: 28671695; PMCID: PMC5529245. 
  55. Cho JR, Treweek JB, Robinson JE, Xiao C, Bremner LR, Greenbaum A, Gradinaru V. Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli. Neuron. 2017 Jun 21;94(6):1205-1219.e8. doi: 10.1016/j.neuron.2017.05.020. Epub 2017 Jun 8. PMID: 28602690. 
  56. Allen WE, Kauvar IV, Chen MZ, Richman EB, Yang SJ, Chan K, Gradinaru V, Deverman BE, Luo L, Deisseroth K. Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex. Neuron. 2017 May 17;94(4):891-907.e6. doi: 10.1016/j.neuron.2017.04.017. PMID: 28521139; PMCID: PMC5723385. 
  57. Greenbaum A, Chan KY, Dobreva T, Brown D, Balani DH, Boyce R, Kronenberg HM, McBride HJ, Gradinaru V. Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow. Sci Transl Med. 2017 Apr 26;9(387):eaah6518. doi: 10.1126/scitranslmed.aah6518. PMID: 28446689. 
  58. Bedbrook CN, Rice AJ, Yang KK, Ding X, Chen S, LeProust EM, Gradinaru V, Arnold FH. Structure-guided SCHEMA recombination generates diverse chimeric channelrhodopsins. Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):E2624-E2633. doi: 10.1073/pnas.1700269114. Epub 2017 Mar 10. PMID: 28283661; PMCID: PMC5380088. 
  59. Herwig L, Rice AJ, Bedbrook CN, Zhang RK, Lignell A, Cahn JKB, Renata H, Dodani SC, Cho I, Cai L, Gradinaru V, Arnold FH. Directed Evolution of a Bright Near-Infrared Fluorescent Rhodopsin Using a Synthetic Chromophore. Cell Chem Biol. 2017 Mar 16;24(3):415-425. doi: 10.1016/j.chembiol.2017.02.008. Epub 2017 Mar 2. PMID: 28262559; PMCID: PMC5357175. 
  60. Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell. 2016 Dec 1;167(6):1469-1480.e12. doi: 10.1016/j.cell.2016.11.018. PMID: 27912057; PMCID: PMC5718049. 
  61. DePas WH, Starwalt-Lee R, Van Sambeek L, Ravindra Kumar S, Gradinaru V, Newman DK. Exposing the Three-Dimensional Biogeography and Metabolic States of Pathogens in Cystic Fibrosis Sputum via Hydrogel Embedding, Clearing, and rRNA Labeling. mBio. 2016 Sep 27;7(5):e00796-16. doi: 10.1128/mBio.00796-16. PMID: 27677788; PMCID: PMC5040109. 
  62. Pan M, Reid MA, Lowman XH, Kulkarni RP, Tran TQ, Liu X, Yang Y, Hernandez- Davies JE, Rosales KK, Li H, Hugo W, Song C, Xu X, Schones DE, Ann DK, Gradinaru V, Lo RS, Locasale JW, Kong M. Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nat Cell Biol. 2016 Oct;18(10):1090-101. doi: 10.1038/ncb3410. Epub 2016 Sep 12. PMID: 27617932; PMCID: PMC5536113. 
  63. Treweek JB, Gradinaru V. Extracting structural and functional features of widely distributed biological circuits with single cell resolution via tissue clearing and delivery vectors. Curr Opin Biotechnol. 2016 Aug;40:193-207. doi: 10.1016/j.copbio.2016.03.012. Epub 2016 Jul 6. PMID: 27393829; PMCID: PMC4975678. 
  64. Shah S, Lubeck E, Schwarzkopf M, He TF, Greenbaum A, Sohn CH, Lignell A, Choi HM, Gradinaru V, Pierce NA, Cai L. Single-molecule RNA detection at depth by hybridization chain reaction and tissue hydrogel embedding and clearing. Development. 2016 Aug 1;143(15):2862-7. doi: 10.1242/dev.138560. Epub 2016 Jun 24. PMID: 27342713; PMCID: PMC5004914. 
  65. Xiao C, Cho JR, Zhou C, Treweek JB, Chan K, McKinney SL, Yang B, Gradinaru V. Cholinergic Mesopontine Signals Govern Locomotion and Reward through Dissociable Midbrain Pathways. Neuron. 2016 Apr 20;90(2):333-47. doi: 10.1016/j.neuron.2016.03.028. PMID: 27100197; PMCID: PMC4840478. 
  66. Deverman BE, Pravdo PL, Simpson BP, Kumar SR, Chan KY, Banerjee A, Wu WL, Yang B, Huber N, Pasca SP, Gradinaru V. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. Nat Biotechnol. 2016 Feb;34(2):204-9. doi: 10.1038/nbt.3440. Epub 2016 Feb 1. PMID: 26829320; PMCID: PMC5088052. 
  67. Gradinaru V, Flytzanis NC. Neuroscience: Fluorescent boost for voltage sensors. Nature. 2016 Jan 28;529(7587):469-70. doi: 10.1038/529469a. PMID: 26819038. 
  68. Skennerton CT, Ward LM, Michel A, Metcalfe K, Valiente C, Mullin S, Chan KY, Gradinaru V, Orphan VJ. Genomic Reconstruction of an Uncultured Hydrothermal Vent Gammaproteobacterial Methanotroph (Family Methylothermaceae) Indicates Multiple Adaptations to Oxygen Limitation. Front Microbiol. 2015 Dec 23;6:1425. doi: 10.3389/fmicb.2015.01425. PMID: 26779119; PMCID: PMC4688376. 
  69. Treweek JB, Chan KY, Flytzanis NC, Yang B, Deverman BE, Greenbaum A, Lignell A, Xiao C, Cai L, Ladinsky MS, Bjorkman PJ, Fowlkes CC, Gradinaru V. Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping. Nat Protoc. 2015 Nov;10(11):1860-1896. doi: 10.1038/nprot.2015.122. Epub 2015 Oct 22. PMID: 26492141; PMCID: PMC4917295. 
  70. Bedbrook CN, Kato M, Ravindra Kumar S, Lakshmanan A, Nath RD, Sun F, Sternberg PW, Arnold FH, Gradinaru V. Genetically Encoded Spy Peptide Fusion System to Detect Plasma Membrane-Localized Proteins In Vivo. Chem Biol. 2015 Aug 20;22(8):1108-21. doi: 10.1016/j.chembiol.2015.06.020. Epub 2015 Jul 23. PMID: 26211362; PMCID: PMC4546540. 
  71. Flytzanis NC, Bedbrook CN, Chiu H, Engqvist MK, Xiao C, Chan KY, Sternberg PW, Arnold FH, Gradinaru V. Archaerhodopsin variants with enhanced voltage- sensitive fluorescence in mammalian and Caenorhabditis elegans neurons. Nat Commun. 2014 Sep 15;5:4894. doi: 10.1038/ncomms5894. PMID: 25222271; PMCID: PMC4166526. 
  72. McIsaac RS, Engqvist MK, Wannier T, Rosenthal AZ, Herwig L, Flytzanis NC, Imasheva ES, Lanyi JK, Balashov SP, Gradinaru V, Arnold FH. Directed evolution of a far-red fluorescent rhodopsin. Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13034-9. doi: 10.1073/pnas.1413987111. Epub 2014 Aug 25. PMID: 25157169; PMCID: PMC4246972. 
  73. Yang B, Treweek JB, Kulkarni RP, Deverman BE, Chen CK, Lubeck E, Shah S, Cai L, Gradinaru V. Single-cell phenotyping within transparent intact tissue through whole-body clearing. Cell. 2014 Aug 14;158(4):945-958. doi: 10.1016/j.cell.2014.07.017. Epub 2014 Jul 31. PMID: 25088144; PMCID: PMC4153367. 
  74. Birmingham K, Gradinaru V, Anikeeva P, Grill WM, Pikov V, McLaughlin B, Pasricha P, Weber D, Ludwig K, Famm K. Bioelectronic medicines: a research roadmap. Nat Rev Drug Discov. 2014 Jun;13(6):399-400. doi: 10.1038/nrd4351. PMID: 24875080. 
  75. Sukhotinsky I, Chan AM, Ahmed OJ, Rao VR, Gradinaru V, Ramakrishnan C, Deisseroth K, Majewska AK, Cash SS. Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model. PLoS One. 2013 Apr 24;8(4):e62013. doi: 10.1371/journal.pone.0062013. PMID: 23637949; PMCID: PMC3634849. 
  76. Chung K, Wallace J, Kim SY, Kalyanasundaram S, Andalman AS, Davidson TJ, Mirzabekov JJ, Zalocusky KA, Mattis J, Denisin AK, Pak S, Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V, Deisseroth K. Structural and molecular interrogation of intact biological systems. Nature. 2013 May 16;497(7449):332-7. doi: 10.1038/nature12107. Epub 2013 Apr 10. PMID: 23575631; PMCID: PMC4092167. 
  77. Mattis J, Tye KM, Ferenczi EA, Ramakrishnan C, O’Shea DJ, Prakash R, Gunaydin LA, Hyun M, Fenno LE, Gradinaru V, Yizhar O, Deisseroth K. Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins. Nat Methods. 2011 Dec 18;9(2):159-72. doi: 10.1038/nmeth.1808. PMID: 22179551; PMCID: PMC4165888. 
  78. Domingos AI, Vaynshteyn J, Voss HU, Ren X, Gradinaru V, Zang F, Deisseroth K, de Araujo IE, Friedman J. Leptin regulates the reward value of nutrient. Nat Neurosci. 2011 Nov 13;14(12):1562-8. doi: 10.1038/nn.2977. PMID: 22081158; PMCID: PMC4238286. 
  79. Goshen I, Brodsky M, Prakash R, Wallace J, Gradinaru V, Ramakrishnan C, Deisseroth K. Dynamics of retrieval strategies for remote memories. Cell. 2011 Oct 28;147(3):678-89. doi: 10.1016/j.cell.2011.09.033. Epub 2011 Oct 20. PMID: 22019004. 
  80. Tye KM, Prakash R, Kim SY, Fenno LE, Grosenick L, Zarabi H, Thompson KR, Gradinaru V, Ramakrishnan C, Deisseroth K. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature. 2011 Mar 17;471(7338):358-62. doi: 10.1038/nature09820. Epub 2011 Mar 9. PMID: 21389985; PMCID: PMC3154022. 
  81. Witten IB, Lin SC, Brodsky M, Prakash R, Diester I, Anikeeva P, Gradinaru V, Ramakrishnan C, Deisseroth K. Cholinergic interneurons control local circuit activity and cocaine conditioning. Science. 2010 Dec 17;330(6011):1677-81. doi: 10.1126/science.1193771. PMID: 21164015; PMCID: PMC3142356. 
  82. Lee JH, Durand R, Gradinaru V, Zhang F, Goshen I, Kim DS, Fenno LE, Ramakrishnan C, Deisseroth K. Global and local fMRI signals driven by neurons defined optogenetically by type and wiring. Nature. 2010 Jun 10;465(7299):788-92. doi: 10.1038/nature09108. PMID: 20473285; PMCID: PMC3177305. 
  83. Gradinaru V, Zhang F, Ramakrishnan C, Mattis J, Prakash R, Diester I, Goshen I, Thompson KR, Deisseroth K. Molecular and cellular approaches for diversifying and extending optogenetics. Cell. 2010 Apr 2;141(1):154-165. doi: 10.1016/j.cell.2010.02.037. Epub 2010 Mar 18. PMID: 20303157; PMCID: PMC4160532. 
  84. Zhang F, Gradinaru V, Adamantidis AR, Durand R, Airan RD, de Lecea L, Deisseroth K. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc. 2010 Mar;5(3):439-56. doi: 10.1038/nprot.2009.226. Epub 2010 Feb 18. PMID: 20203662; PMCID: PMC4503465. 
  85. Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K. Optical deconstruction of parkinsonian neural circuitry. Science. 2009 Apr 17;324(5925):354-9. doi: 10.1126/science.1167093. Epub 2009 Mar 19. PMID: 19299587; PMCID: PMC6744370. 
  86. Gradinaru V, Thompson KR, Deisseroth K. eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications. Brain Cell Biol. 2008 Aug;36(1-4):129-39. doi: 10.1007/s11068-008-9027-6. Epub 2008 Aug 2. PMID: 18677566; PMCID: PMC2588488. 
  87. Schneider MB, Gradinaru V, Zhang F, Deisseroth K. Controlling neuronal activity. Am J Psychiatry. 2008 May;165(5):562. doi: 10.1176/appi.ajp.2008.08030444. PMID: 18450936. 
  88. Gradinaru V, Thompson KR, Zhang F, Mogri M, Kay K, Schneider MB, Deisseroth K. Targeting and readout strategies for fast optical neural control in vitro and in vivo. J Neurosci. 2007 Dec 26;27(52):14231-8. doi: 10.1523/JNEUROSCI.3578-07.2007. PMID: 18160630; PMCID: PMC6673457. 

Selected Patents

  1. Flynn MJ, Elowitz MB, Hori A, Gradinaru V, “Method for Robust Control of Gene Expression.” 2021 (pending)
  2. Gradinaru V, Kumar SR, Deverman B, “Virus Compositions with Enhanced Specificity in the Brain.” 2019 (pending)
  3. Gradinaru V, Flytzanis NC, Goeden NS, “Adeno-associated Virus Compositions for Targeted Gene Therapy.” 2018 (pending)
  4. Gradinaru V, Chan KY, Grinbaum A, “Methods and Devices for Soft and Osseous Tissue Clearing and Fluorescent Imaging.” 2018 (pending)
  5. Deisseroth K, Aden ER, Gradinaru V, Delp SL, “Compositions and Methods for Treating Neurogenic Disorders of the Pelvic Floor.” 2016 (pending)
  6. Deisseroth K, Gradinaru V, “Functional Targeted Brain Endoskeletonization.” 2016 (pending)
  7. Deverman BE, Gradinaru V, Chan KY, “Novel Adeno-associated Viral Capsid Variants for Widespread Gene Delivery to the Peripheral Nervous System, Heart and Central Nervous System.” 2016 (pending)
  8. Gradinaru V, Treweek J, “Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping.” 2020
  9. Deverman BE, Patterson PH, Gradinaru V, “Selective Recovery.” 2018
  10. Gradinaru V, Yang B, “Methods for Phenotyping of Intact Whole Tissues.” 2017
  11. Deverman BE, Patterson PH, Gradinaru V, “Recombinant AAV Capsid Protein.” 2017
  12. Deisseroth K, Zhang F, Gradinaru V, Schneider MB, “Cell Line for Optically-based Screening of Ion Channel Modulators.” 2016
  13. Deisseroth K, Zhang F, Gradinaru V, “System utilizing Volvox carteri light-activated ion channel protein (VChR1) for optical stimulation of target cells.”
  14. Deisseroth K, Zhang F, Gradinaru V, “Method for optically controlling a neuron with a mammalian codon optimized nucleotide sequence that encodes a variant opsin polypeptide derived from Natromonas pharaonis NpHR.” 2018
  15. Deisseroth K, Zhang F, Gradinaru V, “Light-sensitive ion-passing molecules.” 2017
  16. Deisseroth K, Zhang F, Gradinaru V, “Methods for treating Parkinson’s disease by optically stimulating target cells.” 2016
  17. Deisseroth K, Zhang F, Gradinaru V, “Opsin polypeptides and methods of use thereof.” 2016