The Hauswirth Lab

Dr. Hauswirth's Lab

Principal Investigator

Wiliam Hauswirth, PhD
Professor and Maida and Morris Rybaczki Eminent Scholar Chair in Ophthalmic Sciences

 

Contact Information

(352) 359-4301

hauswrth@ufl.edu

 

About the PI

Dr. Hauswirth received his B.S. in Chemistry from Stanford University and his Ph.D in Physical Chemistry from Oregon State University.  After an NIH Fellowship in the Biochemistry Department at the Johns Hopkins University, he joined that department as an Assistant Professor.  In 1976, he joined the faculty of Molecular Genetics and in 1985 joined the Ophthalmology faculty at the University of Florida College of Medicine.  Over the past 30 years he has received short-term professorships from Oxford University, University of Edinburgh, University of Paris and University of Pavia.

Dr. Hauswirth has authored over 395 original articles and reviews, and is currently on the editorial boards of several journals.  He has served as a member of research grant review panels for several NIH Institutes, the NSF, the USDA, the National Geographic Society, the American Heart Association, the March of Dimes, the Foundation Fighting Blindness and the Macula Vision Research Foundation as well as consulted on research grants for the United Kingdom, France, Italy, Japan, Belgium, Denmark, Finland, India and Kuwait. He is currently on the Scientific Boards of Applied Genetic Technologies Corp. and the BCM Families Foundation.  He was awarded the 2001 Alcon Award for Vision Research, the 2002 Foundation Fighting Blindness Trustees Award, the 2004 John Kayser International Award for Retinal Research, 2005 FASEB award for lifetime achievement in vision research, the 2011 Foundation Fighting Blindness Director’s Award and the 2011 International Gold Award of the Chinese Ophthalmological Society, the Llura Liggett Gund Award for Lifetime Achievement from the Fdn. Fighting Blindness, the Human Gene Therapy 25th Anniversary Pioneer Award, the 2014 Ophthalmology Innovator of the Year Award by the OIS/AAO, and the 2018 Champalimaud Award for Vision Science.

Additionally, Dr. Hauswirth was voted the 2005 Scientist of the Year by the Hope for Vision Foundation, Florida Scientist of the Year in 2009, his work recognized as Time Magazine’s third most important science discovery for 2009, cited in “A Decade of Breakthroughs” by Science Magazine in 2011, and invited by the Pope to speak on his work at the Vatican in 2016.

Lab Staff

Wen-Tao Deng, PhD
Frank Dyka, PhD
Jie Li, PhD
Vince Chiodo, BS
Ping Zsu, BS

Areas of Interest:

  • AAV mediated gene therapy for vision and hearing diseases
  • Childhood forms of severe genetic vision and hearing loss

Research Summary

Dr Hauswirth has a long-term interest in the delivery and testing of potentially therapeutic genes for Dominant, Recessive and X-Linked Retinitis Pigmentosa, Leber Congenital Amaurosis, Achromatopsia, Blue Cone Monochromacy, Usher’s Disease, Macular Degeneration, Diabetic Retinopathy, Glaucoma and Optic Neuropathies in natural and transgenic animal models of each human disease. He has been/is principal investigator on numerous NIH and private foundation grants supporting this work. He was also coPI on a related clinical trial grant for LCA2 in which the patients began treatment in 2007 and for which NIH funded follow-up continues presently.  He is also currently PI on a multicenter NIH grant to bring gene therapy for Achromatopsia into clinical testing.  Over the past six years he has also generated successful proof of principle gene therapy in animal models for the A3 and B3 forms of Achromatopsia, the RPGR form of X-linked RP, rhodopsin autosomal dominant RP, the ND4 form of Leber Hereditary Optic Neuropathy, Best Macular Dystrophy, Usher 1B, LCA1 and MERTK disease. Overall, more than 390 peer reviewed papers have been published.  Through NIH, University and Biotech collaborations the A3 and B3 forms of Achromatopsia, the RPGR form of X-linked RP, the ND4 form of Leber Hereditary Optic Neuropathy, LCA1, MERTK disease as well as X-linked Retinoschisis are in early phase gene therapy clinical trials or on a clinical trial trajectory.  Finally, he collaborates with more than 70 PI’s around the world, by designing and providing AAV vectors (~100 per year) for disorders affecting essentially all parts of the eye.

Grants

Grant Identifier: R24 EY022023 (Hauswirth)   6/01/13-5/31/19 Sponsor: NEI
Title of Grant: rAAV-CNGB3 Gene Therapy for Achromatopsia: Translational Research Studies

Goals of Grant: Develop an AAV mediated gene therapy for the B3 form of Achromatopsia through the IND approval stage for a Phase I/II gene therapy clinical trial. Four clinical sites are involved.

William Hauswirth, PhD – PI

Grant Identifier: NA (Hauswirth) 1/01/13-12/31/21 Sponsor: Macular Vision Research Foundation
Title of Grant: Gene Therapy for Blue Cone Monochromacy (BCM)

Goals of Grant: Carry out efficacy and safety studies for BCM gene therapy in rat and mouse models.

William Hauswirth, PhD – PI

Grant Identifier: R01 EY017549 (Aguirre)    9/01/17-8/31/22 Sponsor: NEI
Title of Grant: Translational Research for Retinal Degeneration Therapies

Goals of Grant: Produce custom AAV vectors for testing gene therapy in RP and LCA dog models.

William Hauswirth, PhD – coPI

Grant Identifier: R01 EY026268 (Lewin)    9/01/17-8/31/22 Sponsor: NEI
Title of Grant: Models of Geographic Atrophy

Goals of Grant: Produce custom AAV vectors for testing gene therapy for GA on rodent models.

William Hauswirth, PhD – coPI

Grant Identifier: AGTC SRA 8/01/18-7/31/19 Sponsor: AGTC
Title of Grant: Gene Therapy for ABCA4 Stargardt Disease

Goals of Grant: Develop and test AAV dual vectors for ABCA4 disease gene therapy in the knock-out mouse.

William Hauswirth, PhD –  PI

Issued Patents

  1. US Patent No. 5,874,304. February 23, 1999. Humanized Green Fluorescent Protein Genes and Methods.
  2. US Patent No. 5,968,750. October 19, 1999. Humanized Green Fluorescent Protein Genes and Methods.
  3. US Patent No. 6,020,192. February 01, 2000. Humanized Green Fluorescent Protein Genes and Methods.
  4. US Patent No. 6,225,291. May 01, 2001. Rod Opsin mRNA-Specific Ribozyme Compositions and Methods for the Treatment of Retinal Diseases.
  5. US Patent No. 7,094,604. August 22, 2006. Production of Pseudotyped Recombinant AAV Virions.
  6. US Patent No. 7,342,111. March 11, 2008. AAV-Delivered Ribozymes Compositions and Methods of Use
  7. US Patent No. 8,147,823. April 03, 2012. Method of Treating or Retarding the Development of Blindness
  8. US Patent No. 8,298,818. October 30, 2012. A Self-Complementary Adeno-Associated Virus Having a Truncated CMV-Chicken B-Actin Promoter.
  9. US Patent No. 9,198,595. December 01, 2015. Regents and Methods for Modulating Cone Photoreceptor Activity.
  10. US Patent No. 9,375,491. Junes 28, 2016. Chimeric Promoter for Cone Photoreceptor Targeted Gene Therapy.
  11. US Patent No.9,433,688. September 06, 2016. Method of Treating or Retarding the Development of Blindness.
  12. US Patent No. 9,770,491. September 26, 2017. AAV-Mediated Gene Therapy for RPGR X-Linked Retinal Degeneration.
  13. US Patent No. 9,816,108. November 14, 2017. Raav-Guanylate Cyclase Compositions and Methods for Treating Leber’s Congenital Amaurosis-1 (LCA-1).

Recent Publications

Bosco A, Anderson SR, Breen KT, Romero CO, Steele MR, Chiodo VA, Boye SL, Hauswirth WW, Tomlinson S, Vetter M “Complement C3-Targeted Gene Therapy Restricts Onset and Progression of Neurodegeneration in Chronic Mouse Glaucoma.” Mol Ther. 2018 26:2379-96 PMID: 30217731

Cideciyan AV, Sudharsan R, Dufour VL, Massengill MT, Iwabe S, Swider M, Lisi B, Sumaroka A, Marinho LF, Appelbaum T, Rossmiller B, Hauswirth WW, Jacobson SG, Lewin AS, Aguirre GD, Beltran WA. “Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector.” Proc Natl Acad Sci U S A. 2018 Sep 4;115(36):E8547-E8556. doi: 10.1073/pnas.1805055115. Epub 2018 Aug 20. PMID: 30127005

Deng WT, Kolandaivelu S, Dinculescu A, Li J, Zhu P, Chiodo VA, Ramamurthy V, Hauswirth WW. “Cone Phosphodiesterase-6γ’ Subunit Augments Cone PDE6 Holoenzyme Assembly and Stability in a Mouse Model Lacking Both Rod and Cone PDE6 Catalytic Subunits.” Front Mol Neurosci. 2018 Jul 9;11:233. doi: 10.3389/fnmol.2018.00233. eCollection 2018. PMID:30038560

Ofri R, Averbukh E, Ezra-Elia R, Ross M, Honig H, Obolensky A, Rosov A, Hauswirth WW, Gootwine E, Banin E. “Six Years and Counting: Restoration of Photopic Retinal Function and Visual Behavior Following Gene Augmentation Therapy in a Sheep Model of CNGA3 Achromatopsia.”Hum Gene Ther. 2018 Jul 30. doi: 10.1089/hum.2018.076. [Epub ahead of print] PMID:29926749

Yang F, Ma H, Boye SL, Hauswirth WW, Ding XQ. “Overexpression of Type 3 Iodothyronine Deiodinase Reduces Cone Death in the Leber Congenital Amaurosis Model Mice.” Adv Exp Med Biol. 2018;1074:125-131. PMID:29721936

Dinculescu A, Dyka FM, Min SH, Stupay RM, Hooper MJ, Smith WC, Hauswirth WW.  “Co-Expression of Wild-Type and Mutant S163R C1QTNF5 in Retinal Pigment Epithelium.”Adv Exp Med Biol. 2018;1074:61-66. doi: 10.1007/978-3-319-75402-4_8. PMID:29721928

Yu H, Porciatti V, Lewin A, Hauswirth W, Guy, J “Longterm Reversal of Severe Visual Loss by Mitochondrial Gene Transfer in a Mouse Model of Leber Hereditary Optic Neuropathy.” Sci Rep. 2018 Apr 3;8(1):5587. doi: 10.1038/s41598-018-23836-y. PMID:29615737

Guziewicz KE, Cideciyan AV, Beltran WA, Komáromy AM, Dufour VL, Swider M, Iwabe S, Sumaroka A, Kendrick BT, Ruthel G, Chiodo VA, Héon E, Hauswirth WW, Jacobson SG, Aguirre GD. “BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure.”” Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):E2839-E2848. doi: 10.1073/pnas.1720662115. Epub 2018 Mar 5. PMID:29507198

Deng WT, Li J, Zhu P, Chiodo VA, Smith WC, Freedman B, Baehr W, Pang J, Hauswirth WW.“Human L- and M-opsins restore M-cone function in a mouse model for human blue cone monochromacy.”Mol Vis. 2018 Jan 8;24:17-28. eCollection 2018. PMID:29386880

Kady NM, Liu X, Lydic TA, Syed MH, Navitskaya S, Wang Q, Hammer SS, O’Reilly S, Huang C, Seregin SS, Amalfitano A, Chiodo VA, Boye SL, Hauswirth WW, Antonetti DA, Busik JV.  “ELOVL4-Mediated Production of Very Long-Chain Ceramides Stabilizes Tight Junctions and Prevents Diabetes-Induced Retinal Vascular Permeability.” Diabetes. 2018 Apr;67(4):769-781. doi: 10.2337/db17-1034. Epub 2018 Jan 23. PMID:29362226

Petersen-Jones SM, Occelli LM, Winkler PA, Lee W, Sparrow JR, Tsukikawa M, Boye SL, Chiodo V, Capasso JE, Becirovic E, Schön C, Seeliger MW, Levin AV, Michalakis S, Hauswirth WW, Tsang SH.  “Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach.” J Clin Invest. 2018 128:190-206.. Epub 2017 Nov 20. PMID:29202463

Song C, Conlon TJ, Deng WT, Coleman KE, Zhu P, Plummer C, Mandapati S, Hoosear MV, Green KB, Sonnentag P, Sharma AK, Timmers A, Robinson P, Knop DR, Hauswirth WW, Chulay JD, Shearman MS, Ye GJ. “Toxicology and Pharmacology of an AAV Vector Expressing Codon-optimized RPGR in RPGR-deficient Rd9 Mice.”Hum Gene Ther Clin Dev. 2018 Oct 3. doi: 10.1089/humc.2018.168. [Epub ahead of print] PMID:30280954

For more information about Dr. Hauswirth’s lab please contact Dr. Hauswirth’s administrator, Suzi Porterfield at  suzis@ufl.edu