Dieter C. Gruenert, PhD

Dieter C. Gruenert, PhD

Adjunct Professor, Department of Otolaryngology–Head and Neck Surgery, UCSF

Phone: (415) 476-8586
Box 1330, UCSF
San Francisco, CA 94143-1330

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Cancer Center Membership

Associate Member » Breast Oncology

Research Summary

Dieter C. Gruenert, PhD, is a Professor in the Department of Otolaryngology-Head and Neck Surgery. He is also a member of the Eli Edythe Broad Center for Regenerative Medicine and Stem Cell Research, the Institute for Human Genetics, the Helen Diller Family Comprehensive Cancer Center, and the Cardiovascular Research Institute at UCSF as well as an Adjunct Professor in the Department of Pediatrics at the University of Vermont. He received his Ph.D. in Biophysics from UC Berkeley in 1982 and was postdoctoral fellow (1982-1984) in the Department of Carcinogenesis at the Swiss Institute for Experimental Cancer Research in Lausanne, Switzerland. He originally joined the faculty at UCSF in 1986 where he developed many of the human cystic fibrosis (CF) and non-CF airway epithelial cell lines used in CF and airway disease research throughout the world. He was the Co-Director of the Gene Therapy Core Center at UCSF from 1992-1999. In 2000 he left UCSF to take a position as a Professor of Medicine and Director of the Division of Human Molecular Genetics at the University of Vermont, and then returned to the San Francisco area in 2003 to take position as a Senior Scientist at the California Pacific Medical Center Research Institute. In 2005, he established and headed the Stem Cell Research Program at CPMCRI before returning to UCSF 2010 to pursue his interest in developing a regenerative medicine program in OHNS as an adjuvant therapy to surgical intervention.

Dr. Gruenert's present research continues to focus on human cell and molecular biology as they relate to the development of gene and cell-based therapies for ameliorating disease pathologies. His work has expanded the potential of evaluating and screening drugs directed at modifying aberrantly functioning human gene products in human cell systems. These include tissue/cell type specific primary cells, immortalized cells, and induced pluripotent stem cells (iPSCs). In addition, the development of patient-specific parathyroid, thyroid, salivary gland, tracheal and nasal mucosa tissue from iPSCs is a critical component in regenerating intact tissue that are maintain both functional and cosmetic integrity.

In addition to his work on cell systems, Dr. Gruenert’s work has led to development of novel diagnostic and oligo/polynucleotide-based therapeutic strategies and nucleic acid delivery approaches. His oligo/polynucleotide gene repair studies were among the first to demonstrate that genetic mutations at a disease-causing locus in the genomic DNA could be corrected with fragments of DNA and essentially set the stage for the present nuclease mediated gene editing strategies using TALENs and CRISPRs.

Dr. Gruenert has more than 150 publications, holds 5 patents and has given 240 invited presentations worldwide; he reviews grants for numerous national and international agencies and is on the Editorial Boards of a number prestigious scientific journals. His selection as for European Respiratory Society Visiting Professorship at the Necker Hospital in Paris and a Visiting Professorship at Tor Vergata University in Rome as well as his current appointment to the Commission for the National Agency for Evaluation of Candidates of Professor and Associate Professor for the Italian Ministry for Education, Universities and Research in Italy is a reflection of the impact his work has had internationally.

Research Areas:

Gene Targeting: Studies to define SFHR and have led to a new paradigm for viewing homologous replacement in human cells. This research has broadened the understanding the mechanistic underpinnings of homologous replacement in human somatic cells. This work has also led us to pursue investigations into the development of transgenic large animal models of disease.

DNA Delivery: Studies have also focused on non-viral delivery systems ranging from liposomes, polyamidoamines, polyethyleneimines, microinjection, and electroporation for in vitro, in vivo and ex vivo DNA delivery. These studies are critical for identifying viable alternatives to the virally-based approaches for therapeutically delivering DNA into cells and tissue.

Cancer Gene Therapy: Studies to evaluate the role of connexins in “bystander killing” observed with suicide genes have been undertaken in human epithelial cells and in brain tumor cells. As an outgrowth of this work, connexin genes in both transformed and non-transformed cells have been studied to characterize the role of intercellular communication in modulating neoplastic progression. Cell lines will also be developed from tissue samples head and neck cancers (e.g., endocrine, salivary, squamous) to evaluate the molecular genetic features of specific tumor types and their sensitivity to therapeutic agents.

Development of Breast Cancer Therapeutic Strategies: Studies have begun to develop a combined therapy based on the killing of hypoxic cells using suicide gene and shRNA inhibition of VEGF. These systems will be evaluated in vitro and in vivo for their ability to enhance the effectiveness of tumor cell killing. In addition, poly (ADP-ribose) polymerase inhibitor (PARPi) sensitivity and resistance in BRCA2 mutant mammary cells is being evaluated in primary and tumor-derived mammary epithelial cells as well as somatic cell derived iPS cells.

Epithelial Cell and Molecular Biology/Cell Transformation: The generation and characterization of immortalized cell lines for human genetic disorders and cancer is ongoing. The cells lines are tools to investigate biological pathways associated with various diseases and to develop therapeutic strategies. The cell lines developed in my laboratory have been used internationally to elucidate the cellular and genetic mechanisms that underlie human airway epithelial cell biology and disease pathology, genetic disorders, and cancer biology.

Stem Cell-Based Tissue Repair: Studies have been undertaken to evaluate the patient-specific therapeutic potential of adult and pluripotent (embryonic and induced) stem cells. In addition, induced pluripotent stem (iPS) cells from CF and SCD individuals have been generated. Enrichment and the determinants for multilineage differentiation are now under investigation. These studies are of particularly relevant for the repair of organ damage caused by a chronic (genetic or non-genetic), an acute traumatic episode, or therapeutic surgery for tumor removal.


Head and Neck Cell Biology and Stem Cell Therapeutics


Cell and molecular biology, DNA repair and replication, stem cell biology, carcinogenesis, airway epithelial cell biology, ion transport, photobiology, radiation biophysics, human airway physiology, molecular genetics, cystic fibrosis, sickle cell anemia

Professional Interests:

Development of tissue/cell type-specific cell systems (primary, immortalized and induced pluripotent stem cell (iPSC)), gene repair/editing, nucleic acid delivery, gene and cell therapy, stem cell-based tissue repair systems, long noncoding RNA (lncRNA) regulation of gene expression

Education and Training:

• PhD: University of California, Berkeley –Biophysics

• Postdoctoral: Swiss Institute for Experimental Cancer Research, Epalinges/Lausanne, Switzerland

Awards and Honors:

• 1971-72 President, Student Memorial Union, University of Wisconsin, Madison

• 1988 Workshop Mod, "Cell Immortalization," 2nd North Amer CF Conf, Orlando, FL

• 1990 Conf Chair, NIDDK Workshop, "Epithelial Cell Growth and Transformation", University of California, San Francisco, CA

• 1990 Roundtable Moderator, 4th Annual North American CF Conf

• 1991 Roundtable Moderator, 5th Annual North American CF Conf

• 1995-12 Advisor, DNA Files, Sound Visions Productions, Berkeley CA

• 1996-03 Genetics Advisor, International Association of CF Adults

• 1997 Session Chair, Pathophysiology, 21st Eur CF Conf, Davos, Switzerland

• 1997 Conf Chair, “Gene Therapy: The Next Generation”, Intl Cong, Paris, France

• 1998 Session Chair, Emerging Technics, 6th Symp on Gene Therapy, Max Delbrück Cent, Berlin-Buch, Germany

• 1998 Plenary Lecture, “Gene Targeting: Prospects for CF Gene Therapy”, 22nd Eur CF Conf, Berlin, Germany

• 1998 Session Chair, Gene Therapy, 22nd Eur Cystic Fibrosis Conf, Berlin, Germany

• 1998 Session Chair, Genetics and Gene Therapy, Intl Assoc of CF Adults Conf, Berlin, Germany

• 1999 Plenary Lecture and Session Chair, Gene Therapy and Molecular Biology and Medicine Intl Conf, Redwood City, CA

• 1999 Visiting Professorship, University of Rome, Tor Vergata, Department of Biopathology and Diagnostic Imaging, Rome, Italy

• 2001 Conf Chair, "Genome Medicine: Gene Therapy for the Millennium," Rome, Italy

• 2002 Session Chair, "NonViral Gene Therapy: Recent Advances", Amer Soc Gene Therapy Mtg, Boston, MA

• 2002 Session Chair, "Recent Advances in CF Gene Therapy". Eur CF Soc Mtg, Genoa, Italy

• 2003 Session Co-Chair, "NonViral Gene Therapy: Recent Advances", Amer Soc Gene Therapy Mtg, Washington, DC

• 2005 Session Chair, "Oligonucleotide-mediated Therapies", Amer Soc Gene Therapy Mtg, St Louis, MO

• 2005 Moderator, Round Table: Animal Models of CF, North Amer CF Conf, Baltimore, MD.

• 2005 Visiting Professorship, University of Rome, TorVergata, Dipartimento di Medicina di Laboratorio Azienda Ospedaliera, Universitaria “Tor Vergata”, Rome, Italy.

• 2006-08 Chair, Ethics Committee, Amer Soc for Gene and Cell Therapy

• 2007 Keynote speaker, “Modification of Genomic DNA Following Microinjection and Nucleofection of Large Oligodeoxynucleotides”, Australian Soc of Gene Therapy, Canberra, Australia.

• 2007 Session Chair, “Oligonucleotide Based Therapies: Diversity of Oligonucleotides in Gene Therapy”. Amer Soc of Gene Therapy Meeting, Seattle, Washington.

• 2007 Conf Co-Organizer, “Epithelial Cells & Tissues: Production, Cultivation and Characterization”, Lisboa, Portugal.

• 2008-11 Board of Directors, Oligonucleotide Therapeutics Society

• 2009 Eur Respiratory Soc Visiting Professorship, Hôpital Necker - Enfants Malades, INSERM U845, Paris, France

• 2010 Symp Speaker, “Modification of CF and Sickle Cell iPS Cells by SFHR”, Amer Soc for Gene and Cell Therapy Mtg, Washington, DC

• 2010 Session Chair, “Oligonucleotide and RNAi Therapeutics”, Amer Soc for Gene and Cell Therapy Mtg, Washington, DC

• 2010 Session Chair, “Oligonucleotides and Stem Cells”, Oligonucleotide Therapeutics Soc Mtg, Dana Point, CA

• 2011 Session Chair, “Targeting Genetic Diseases”, Oligonucleotide Therapeutics Soc Mtg, Copenhagen, Denmark

• 2011-pres Senior Editor, Nucleic Acid Therapeutics (formerly Oligonucleotides)

• 2012 Session Chair, “Optimizing Cell Line Development: Facilitating the Success of Biologics”, CHI BioProcessing Summit: Optimizing Mammalian Cell Lines, Boston, MA

• 2012 Visiting Professorship, University of Rome, Tor Vergata, Department of Biopathology and Diagnostic Imaging, Rome, Italy

• 2012-pres Appointed Member, Natl Scientific Qualification Committee, Natl Agency for Evaluation of Universities and Res Inst, Italian Ministry of Education, University, and Research.

• 2013-pres Deputy Editor, Molecular Therapy Nucleic Acids

• 2014-pres Co-Executive Editor (Founding Co-Editor), Journal of Biological Methods

• 2015-16 Scientific Advisory Council, Oligonucleotide Therapeutics Society


University of Wisconsin, Madison, B.A., 1972, Molecular Biology
University of California, Berkeley, Ph.D., 1982, Biophysics
Institut Suisse de Recherches, Experimentales sur le Cancer, Epalinges/Lausanne, Suisse, Postdoc, 1982-1984, Carcinogenesis

Professional Experience

  • 1984-1986
    Molecular Biologist, Therapeutic Division, Hana Biologics, Inc., Berkeley, CA
  • 1986-1989
    Assistant Research Biochemist, Cardiovascular Research Institute, UCSF
  • 1990-2000
    Assistant Professor, Associate Professor, and Professor, Depts. of Lab Medicine and Stomatology, UCSF
  • 1990-2000
    Member Graduate Group in Biophysics, UCSF
  • 1991-2000
    Associate Staff, Cardiovascular Research Institute, UCSF
  • 1993-2000
    Associate Director, Gene Therapy Core Center, UCSF
  • 1996-2000
    Member, Program in Biomedical Sciences, UCSF
  • 1999
    Visiting Professor, Tor Vergata Univ., Dept. of Biopathology and Diag. Imaging, Rome, Italy
  • 2000-2003
    Member, Vermont Cancer Center
  • 2000-2003
    Director and Professor, Human Molecular Genetics, Department of Medicine, Univ of Vermont
  • 2003-2010
    Senior Scientist, California Pacific Medical Center Research Institute, San Francisco, CA
  • 2005-2010
    Head, Stem Cell Research Program, California Pacific Medical Center Research Institute, San Francisco, CA
  • 2005-2010
    Chair, SCRO Committee, California Pacific Medical Center Research Institute, San Francisco, CA
  • 2003-present
    Adjunct Professor, Department of Medicine, University of Vermont
  • 2004-present
    Adjunct Professor, Dept of Laboratory Medicine, University of California, San Francisco
  • 2006-present
    Visiting Professor, Tor Vergata Univ., Dept. of Biopathology and Diag. Imaging, Rome, Italy
  • 2009
    European Respiratory Soc Visiting Professor, Necker Hospital for Sick Children, Paris, France
  • 2010-present
    Adjunct Professor, Department of Otolaryngology–Head and Neck Surgery, UCSF

Selected Publications

  1. Suzuki S, Sargent RG, Illek B, Fischer H, Esmaeili-Shandiz A, Yezzi MJ, Lee A, Yang Y, Kim S, Renz P, Qi Z, Yu J, Muench MO, Beyer AI, Guimarães AO, Ye L, Chang J, Fine EJ, Cradick TJ, Bao G, Rahdar M, Porteus MH, Shuto T, Kai H, Kan YW, Gruenert DC. TALENs Facilitate Single-step Seamless SDF Correction of F508del CFTR in Airway Epithelial Submucosal Gland Cell-derived CF-iPSCs. Mol Ther Nucleic Acids. 2016; 5:e273.
    View on PubMed
  2. Nimishakavi S, Raymond WW, Gruenert DC, Caughey GH. Divergent Inhibitor Susceptibility among Airway Lumen-Accessible Tryptic Proteases. PLoS One. 2015; 10(10):e0141169.
    View on PubMed
  3. Jia J, Furlan A, Gonzalez-Hilarion S, Leroy C, Gruenert DC, Tulasne D, Lejeune F. Caspases shutdown nonsense-mediated mRNA decay during apoptosis. Cell Death Differ. 2015 Nov; 22(11):1754-63.
    View on PubMed
  4. Sargent RG, Suzuki S, Gruenert DC. Nuclease-mediated double-strand break (DSB) enhancement of small fragment homologous recombination (SFHR) gene modification in human-induced pluripotent stem cells (hiPSCs). Methods Mol Biol. 2014; 1114:279-90.
    View on PubMed
  5. Blanchard E, Zlock L, Lao A, Mika D, Namkung W, Xie M, Scheitrum C, Gruenert DC, Verkman AS, Finkbeiner WE, Conti M, Richter W. Anchored PDE4 regulates chloride conductance in wild-type and ?F508-CFTR human airway epithelia. FASEB J. 2014 Feb; 28(2):791-801.
    View on PubMed
  6. Kelly C, Canning P, Buchanan PJ, Williams MT, Brown V, Gruenert DC, Elborn JS, Ennis M, Schock BC. Toll-like receptor 4 is not targeted to the lysosome in cystic fibrosis airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2013 Mar 1; 304(5):L371-82.
    View on PubMed
  7. Gonzalez-Hilarion S, Beghyn T, Jia J, Debreuck N, Berte G, Mamchaoui K, Mouly V, Gruenert DC, Déprez B, Lejeune F. Rescue of nonsense mutations by amlexanox in human cells. Orphanet J Rare Dis. 2012; 7:58.
    View on PubMed
  8. Nimishakavi S, Besprozvannaya M, Raymond WW, Craik CS, Gruenert DC, Caughey GH. Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2012 Jul; 303(2):L97-106.
    View on PubMed
  9. Mizunoe S, Shuto T, Suzuki S, Matsumoto C, Watanabe K, Ueno-Shuto K, Suico MA, Onuki K, Gruenert DC, Kai H. Synergism between interleukin (IL)-17 and Toll-like receptor 2 and 4 signals to induce IL-8 expression in cystic fibrosis airway epithelial cells. J Pharmacol Sci. 2012; 118(4):512-20.
    View on PubMed
  10. Gruenert DC, Sargent RG. Virus-mediated Genetic Surgery: Homologous Recombination With a Little "Helper" From My Friends. Mol Ther Nucleic Acids. 2012; 1:e2.
    View on PubMed
  11. de Semir D, Maurisse R, Du F, Xu J, Yang X, Illek B, Gruenert DC. Generation of SV40-transformed rabbit tracheal-epithelial-cell-derived blastocyst by somatic cell nuclear transfer. Cell Tissue Res. 2012 Feb; 347(2):357-67.
    View on PubMed
  12. John G, Chillappagari S, Rubin BK, Gruenert DC, Henke MO. Reduced surface toll-like receptor-4 expression and absent interferon-?-inducible protein-10 induction in cystic fibrosis airway cells. Exp Lung Res. 2011 Aug; 37(6):319-26.
    View on PubMed
  13. Sargent RG, Kim S, Gruenert DC. Oligo/polynucleotide-based gene modification: strategies and therapeutic potential. Oligonucleotides. 2011 Mar-Apr; 21(2):55-75.
    View on PubMed
  14. Illek B, Lei D, Fischer H, Gruenert DC. Sensitivity of chloride efflux vs. transepithelial measurements in mixed CF and normal airway epithelial cell populations. Cell Physiol Biochem. 2010; 26(6):983-90.
    View on PubMed
  15. LeSimple P, Liao J, Robert R, Gruenert DC, Hanrahan JW. Cystic fibrosis transmembrane conductance regulator trafficking modulates the barrier function of airway epithelial cell monolayers. J Physiol. 2010 Apr 15; 588(Pt 8):1195-209.
    View on PubMed
  16. Maurisse R, De Semir D, Emamekhoo H, Bedayat B, Abdolmohammadi A, Parsi H, Gruenert DC. Comparative transfection of DNA into primary and transformed mammalian cells from different lineages. BMC Biotechnol. 2010; 10:9.
    View on PubMed
  17. Bedayat B, Abdolmohamadi A, Ye L, Maurisse R, Parsi H, Schwarz J, Emamekhoo H, Nicklas JA, O'Neill JP, Gruenert DC. Sequence-specific correction of genomic hypoxanthine-guanine phosphoribosyl transferase mutations in lymphoblasts by small fragment homologous replacement. Oligonucleotides. 2010 Feb; 20(1):7-16.
    View on PubMed
  18. Treharne KJ, Xu Z, Chen JH, Best OG, Cassidy DM, Gruenert DC, Hegyi P, Gray MA, Sheppard DN, Kunzelmann K, Mehta A. Inhibition of protein kinase CK2 closes the CFTR Cl channel, but has no effect on the cystic fibrosis mutant deltaF508-CFTR. Cell Physiol Biochem. 2009; 24(5-6):347-60.
    View on PubMed
  19. John G, Yildirim AO, Rubin BK, Gruenert DC, Henke MO. TLR-4-mediated innate immunity is reduced in cystic fibrosis airway cells. Am J Respir Cell Mol Biol. 2010 Apr; 42(4):424-31.
    View on PubMed
  20. Barriere H, Bagdany M, Bossard F, Okiyoneda T, Wojewodka G, Gruenert D, Radzioch D, Lukacs GL. Revisiting the role of cystic fibrosis transmembrane conductance regulator and counterion permeability in the pH regulation of endocytic organelles. Mol Biol Cell. 2009 Jul; 20(13):3125-41.
    View on PubMed

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