Research Summary

For patients seeking treatment for rare genetic diseases and cancer, the standard of care can often be invasive (e.g. organ transplantation or surgical debulking) and temporary (e.g. enzyme replacement therapy or chemotherapy). AAV gene therapies are attractive alternatives as they are non-invasive with long-term therapeutic benefits. However, the success of this new generation of transformative therapies is critically dependent on successful delivery, strong efficacy, improved safety and reduced cost. In the Paulk lab we engineer disruptive technologies to directly address each of these to make AAV cheaper, easier and faster to get these life-saving drugs to the patients who need them.

Dr. Paulk is an Associate Member of UCSF Neurologic Oncology, Member of the UCSF Helen Diller Family Comprehensive Cancer Center, Member of the UCSF Glioblastoma Precision Medicine Program, and Member of the UCSF Liver Center.

Research Funding

  • September 25, 2018 - June 30, 2023 - Human microtissues for in vitro detection and functional measurement of adverse consequences caused by genome editing. , Co-Investigator . Sponsor: NIH/NIBIB, Sponsor Award ID: U01-EB029374
  • June 1, 2020 - June 1, 2021 - A Novel Gene Therapy Platform for Glioblastoma , Principal Investigator . Sponsor: UCSF CATALYST PROGRAM, Sponsor Award ID:
  • August 4, 2016 - May 31, 2021 - Overcoming sexually dimorphic barriers to viral gene therapy for treating genetic liver diseases , Principal Investigator . Sponsor: NIH, Sponsor Award ID: K01DK107607
  • December 12, 2018 - December 11, 2019 - Characterizing the proteomic landscape of rAAV vectors for human liver gene therapies. , Principal Investigator . Sponsor: AMERICAN SOCIETY OF GENE & CELL THERAPY, Sponsor Award ID:

Education

Postdoc, 08/2016 - Human Gene Therapy, Stanford University
PhD, 06/2012 - Viral Gene Therapy, Oregon Health & Science University
BS, 06/2006 - Medical Microbiology, Central Washington University

Selected Publications

  1. Trivedi PD, Yu C, Chaudhuri P, Johnson EJ, Caton T, Adamson L, Byrne BJ, Paulk NK, Clément N. Comparison of highly pure rAAV9 vector stocks produced in suspension by PEI transfection or HSV infection reveals striking quantitative and qualitative differences. Mol Ther Methods Clin Dev. 2022 Mar 10; 24:154-170.  View on PubMed
  2. Martinez-Navio JM, Paulk NK, Gao G. Editorial: "AAV Gene Therapy: Immunology and Immunotherapeutics". Front Immunol. 2021; 12:822389.  View on PubMed
  3. José M. Martinez-Navio, Nicole K. Paulk, Guangping Gao. Editorial: “AAV Gene Therapy: Immunology and Immunotherapeutics”. Frontiers in Immunology. 2021 Dec 21; 12:822389.  View on PubMed
  4. Rumachik NG, Malaker SA, Paulk NK. VectorMOD: Method for Bottom-Up Proteomic Characterization of rAAV Capsid Post-Translational Modifications and Vector Impurities. Front Immunol. 2021; 12:657795.  View on PubMed
  5. Nicole Paulk. Gene Therapy: It Is Time to Talk about High-Dose AAV. Genetic Engineering & Biotechnology News. 2020 Sep 1; 40(9):14-16.  View on PubMed
  6. Neil G. Rumachik, Stacy A. Malaker, Nicole Poweleit, Lucy H. Maynard, Christopher M. Adams, Ryan D. Leib, Giana Cirolia, Dennis Thomas, Susan Stamnes, Kathleen Holt, Patrick Sinn, Andrew P. May, Nicole K. Paulk. Methods Matter -- Standard Production Platforms for Recombinant AAV Produce Chemically and Functionally Distinct Vectors. Molecular Therapy - Methods & Clinical Development. 2020 Sep 1; 18:98-118.  View on PubMed
  7. Rumachik NG, Malaker SA, Poweleit N, Maynard LH, Adams CM, Leib RD, Cirolia G, Thomas D, Stamnes S, Holt K, Sinn P, May AP, Paulk NK. Methods Matter: Standard Production Platforms for Recombinant AAV Produce Chemically and Functionally Distinct Vectors. Mol Ther Methods Clin Dev. 2020 Sep 11; 18:98-118.  View on PubMed
  8. Maynard LH, Smith O, Tilmans NP, Tham E, Hosseinzadeh S, Tan W, Leenay R, May AP, Paulk NK. Fast-Seq: A Simple Method for Rapid and Inexpensive Validation of Packaged Single-Stranded Adeno-Associated Viral Genomes in Academic Settings. Hum Gene Ther Methods. 2019 12; 30(6):195-205.  View on PubMed
  9. Oh Y, Park Y, Cho JH, Wu H, Paulk NK, Liu LX, Kim N, Kay MA, Wu JC, Lin MZ. An orange calcium-modulated bioluminescent indicator for non-invasive activity imaging. Nat Chem Biol. 2019 05; 15(5):433-436.  View on PubMed
  10. Paulk NK, Pekrun K, Charville GW, Maguire-Nguyen K, Wosczyna MN, Xu J, Zhang Y, Lisowski L, Yoo B, Vilches-Moure JG, Lee GK, Shrager JB, Rando TA, Kay MA. Bioengineered Viral Platform for Intramuscular Passive Vaccine Delivery to Human Skeletal Muscle. Mol Ther Methods Clin Dev. 2018 Sep 21; 10:144-155.  View on PubMed
  11. Winters IP, Chiou SH, Paulk NK, McFarland CD, Lalgudi PV, Ma RK, Lisowski L, Connolly AJ, Petrov DA, Kay MA, Winslow MM. Multiplexed in vivo homology-directed repair and tumor barcoding enables parallel quantification of Kras variant oncogenicity. Nat Commun. 2017 12 12; 8(1):2053.  View on PubMed
  12. Puzzo F, Colella P, Biferi MG, Bali D, Paulk NK, Vidal P, Collaud F, Simon-Sola M, Charles S, Hardet R, Leborgne C, Meliani A, Cohen-Tannoudji M, Astord S, Gjata B, Sellier P, van Wittenberghe L, Vignaud A, Boisgerault F, Barkats M, Laforet P, Kay MA, Koeberl DD, Ronzitti G, Mingozzi F. Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase. Sci Transl Med. 2017 Nov 29; 9(418).  View on PubMed
  13. Paulk NK, Pekrun K, Zhu E, Nygaard S, Li B, Xu J, Chu K, Leborgne C, Dane AP, Haft A, Zhang Y, Zhang F, Morton C, Valentine MB, Davidoff AM, Nathwani AC, Mingozzi F, Grompe M, Alexander IE, Lisowski L, Kay MA. Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and Unique Humoral Seroreactivity. Mol Ther. 2018 01 03; 26(1):289-303.  View on PubMed
  14. Barzel A, Paulk NK, Shi Y, Huang Y, Chu K, Zhang F, Valdmanis PN, Spector LP, Porteus MH, Gaensler KM, Kay MA. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature. 2015 Jan 15; 517(7534):360-4.  View on PubMed
  15. Paulk NK, Wursthorn K, Haft A, Pelz C, Clarke G, Newell AH, Olson SB, Harding CO, Finegold MJ, Bateman RL, Witte JF, McClard R, Grompe M. In vivo selection of transplanted hepatocytes by pharmacological inhibition of fumarylacetoacetate hydrolase in wild-type mice. Mol Ther. 2012 Oct; 20(10):1981-7.  View on PubMed
  16. Paulk NK, Loza LM, Finegold MJ, Grompe M. AAV-mediated gene targeting is significantly enhanced by transient inhibition of nonhomologous end joining or the proteasome in vivo. Hum Gene Ther. 2012 Jun; 23(6):658-65.  View on PubMed
  17. Taylor AM, Preston AJ, Paulk NK, Sutherland H, Keenan CM, Wilson PJ, Wlodarski B, Grompe M, Ranganath LR, Gallagher JA, Jarvis JC. Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition. Osteoarthritis Cartilage. 2012 Aug; 20(8):880-6.  View on PubMed
  18. Paulk NK. Novel strategies to improve viral gene targeting and therapeutic liver repopulation in vivo. 2012.  View on PubMed
  19. Paulk NK, Wursthorn K, Wang Z, Finegold MJ, Kay MA, Grompe M. Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo. Hepatology. 2010 Apr; 51(4):1200-8.  View on PubMed
  20. Duncan AW, Hickey RD, Paulk NK, Culberson AJ, Olson SB, Finegold MJ, Grompe M. Ploidy reductions in murine fusion-derived hepatocytes. PLoS Genet. 2009 Feb; 5(2):e1000385.  View on PubMed

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