Research Summary

Daniel Johnson, PhD, is Professor and Vice Chair of Research in the Department of Otolaryngology – Head and Neck Surgery (OHNS) at the University of California, San Francisco. He obtained a bachelor of science in chemistry and a bachelor of arts in mathematics, both from North Park University in Chicago, Illinois. Dr. Johnson earned his MA and PhD in molecular biology from Princeton University, followed by a postdoctoral fellowship at the University of California, San Francisco. Prior to joining UCSF OHNS Department in 2016, Dr. Johnson was a Professor in the Division of Hematology/Oncology, Department of Medicine, and Department of Pharmacology and Chemical Biology at the University of Pittsburgh, Pennsylvania. Dr. Johnson was also the Scientific Director of the Acute Leukemia Working group at the University of Pittsburgh Cancer Institute.

Dr. Johnson has over 120 publications and is Editor of two books, entitled “Cell Death Signaling in Cancer Biology and Treatment” and “Targeting Cell Survival Pathways to Enhance Response to Chemotherapy”. He has maintained continuous NIH funding as a principal investigator since 1995, and has served as a standing member for both NIH and ACS study sections. Dr. Johnson continues to play an active role on multiple review panels for the NIH, VA, and other granting agencies, and serves on the Board of Scientific Counselors for NIH NIDCD. Since 2001 he has served as a Section Editor for Leukemia, the top-ranked journal for hematologic malignancies, and has also served as Editor for Cancer Research and Oncology Research. Dr. Johnson places a high priority on translating findings from his lab to the clinic, and has facilitated the development of clinical trials in both leukemia and head and neck cancer.

Dr. Johnson greatly values teaching and serving as a mentor for individuals with a broad variety of educational backgrounds. He has served as primary mentor or co-mentor for 68 trainees. Most of his trainees have gone on to higher academic or clinical positions, including several who are now faculty members at academic institutions. He was the first lab-based faculty to be awarded the G. David Roodman Excellence in Mentorship Award by the University of Pittsburgh Hematology/Oncology Clinical Fellows. At the University of Pittsburgh he also was a leader for the Career Mentoring Program for junior faculty, and taught extensively in both the graduate and medical schools. He is a faculty member of the BMS Graduate Program at UCSF.

In collaboration with Jennifer Grandis, M.D., Dr. Johnson co-directs the Head and Neck Cancer Lab in the HDFCCC research building.  Work in the Head and Neck Cancer Lab employs multiple model systems to investigate the biology and therapy of head and neck squamous cell carcinoma (HNSCC), including isogenic cell lines, organoids, patient-derived xenograft tumors, genetically engineered mice, and primary patient specimens.  

Dr. Johnson’s research is focused on understanding the molecular mechanisms that contribute to the origin and progression of head and neck squamous cell carcinoma (HNSCC), and the development of novel therapeutic agents and strategies for this disease. He is particularly interested in combating the intrinsic and acquired resistance to anti-cancer agents that characterizes the majority of HNSCC patient tumors. Work from his lab has shown that overexpression of anti-apoptotic Bcl-2 family members and/or hyperactivation of STAT3 transcription factor contribute to HNSCC drug resistance. He has employed small molecule inhibitors of Bcl-2/Bcl-XL/Mcl-1, as well as proteasome inhibitors, to develop synergistic co-targeting strategies to overcome resistance arising for overexpression of Bcl-2 family members. To combat the effects of STAT3 hyperactivation, he has co-invented an highly novel decoy oligonucleotide inhibitor for this previously undruggable oncogene. Current efforts are focused on moving the STAT3 decoy to clinical evaluation in patients with HNSCC. Additional studies in his lab have shown that mutations in caspase-8 protease, which occur frequently in HNSCC tumors, contribute to disease progression by abrogating cell death mediated by death ligands such as TRAIL and TNF. Ongoing studies are aimed at developing further in vivo and organoid models of HNSCC for investigation of drug resistance mechanisms and evaluation of novel precision medicine therapeutic strategies.

Research Funding

  • August 13, 2019 - May 31, 2024 - Targeting STAT3 to enhance anti-tumor immunity, Principal Investigator. Sponsor: NIH/NIDCR, Sponsor Award ID: R01DE028289
  • May 1, 2014 - May 31, 2024 - PI3K Pathway Mutations in Head and Neck Cancer, Co-Principal Investigator. Sponsor: NIH/NIDCR, Sponsor Award ID: R01DE023685
  • January 1, 2016 - December 31, 2020 - Implications of Procaspase-8 Mutations in Oral Squamous Cell Carcinoma, Principal Investigator. Sponsor: NIH/NIDCR, Sponsor Award ID: R01DE024728
  • June 15, 2010 - April 30, 2015 - Molecular Targeting Strategies in HNSCC, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA137260

Education

North Park College, Chicago, IL, B.S.. 05/82, Chemistry
North Park College, Chicago, IL, B.A., 05/82, Mathematics
Princeton University, Princeton, NJ, M.A., 05/84, Molecular Biology
Princeton University, Princeton, NJ, Ph.D., 05/88. Molecular Biology
University of California, San Francisco, CA, Fellow, 12/92, Postdoctoral Fellow

Honors & Awards

  • 1980-1982
    President of Kappa Mu Epsilon, and Illinois Chapter of the National Mathematics Society
  • 1982
    Graduated summa cum laude, North Park College
  • 1988-1992
    Fellow of the Cardiovascular Research Institute, UCSF
  • 1989-1991
    American Heart Association Postdoctoral Fellowship
  • 1994-1995
    Fellow of the Lymphoma Research Foundation of America
  • 1999-present
    Editorial Board, Leukemia
  • 2001-present
    Section Editor, Leukemia
  • 2000-2005
    Member, ACS “Leukemia, Immunology, and Blood Cell Development” Study Section
  • 2006-2009
    Member, NIH Study Section “Drug Discovery and Molecular Pharmacology”
  • 2010-2013
    Editorial Board, Cancer Research
  • 2014
    G. David Roodman Excellence in Mentorship Award from Hematology/Oncology Fellows
  • 2015
    Chair, Special Emphasis Panel for NHLBI SBIR Phase I proposals
  • 2015-present
    Editorial Board, Oncology Research
  •  

Selected Publications

  1. Cui Z, Dabas H, Leonard BC, Shiah JV, Grandis JR, Johnson DE. Caspase-8 mutations associated with head and neck cancer differentially retain functional properties related to TRAIL-induced apoptosis and cytokine induction. Cell Death Dis. 2021 Aug 06; 12(8):775.  View on PubMed
  2. Bhola NE, Njatcha C, Hu L, Lee ED, Shiah JV, Kim MO, Johnson DE, Grandis JR. PD-L1 is upregulated via BRD2 in head and neck squamous cell carcinoma models of acquired cetuximab resistance. Head Neck. 2021 Aug 03.  View on PubMed
  3. Lee RH, Kang H, Yom SS, Smogorzewska A, Johnson DE, Grandis JR. Treatment of Fanconi Anemia-Associated Head and Neck Cancer: Opportunities to Improve Outcomes. Clin Cancer Res. 2021 May 27.  View on PubMed
  4. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020 11 26; 6(1):92.  View on PubMed
  5. Shiah JV, Grandis JR, Johnson DE. Targeting STAT3 with Proteolysis Targeting Chimeras and Next-Generation Antisense Oligonucleotides. Mol Cancer Ther. 2021 02; 20(2):219-228.  View on PubMed
  6. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nature Reviews Disease Primers. In Press. 2020.  View on PubMed
  7. Cui Z, Kang H, Grandis JR, Johnson DE. CYLD Alterations in the Tumorigenesis and Progression of Human Papillomavirus-Associated Head and Neck Cancers. Mol Cancer Res. 2021 01; 19(1):14-24.  View on PubMed
  8. Qureshy Z, Johnson DE, Grandis JR. Targeting the JAK/STAT pathway in solid tumors. J Cancer Metastasis Treat. 2020; 6.  View on PubMed
  9. Izumi H, Wang Z, Goto Y, Ando T, Wu X, Zhang X, Li H, Johnson DE, Grandis JR, Gutkind JS. Pathway-Specific Genome Editing of PI3K/mTOR Tumor Suppressor Genes Reveals that PTEN Loss Contributes to Cetuximab Resistance in Head and Neck Cancer. Mol Cancer Ther. 2020 07; 19(7):1562-1571.  View on PubMed
  10. Lee MJ, Jin N, Grandis JR, Johnson DE. Alterations and molecular targeting of the GSK-3 regulator, PI3K, in head and neck cancer. Biochim Biophys Acta Mol Cell Res. 2020 06; 1867(6):118679.  View on PubMed
  11. O'Keefe RA, Bhola NE, Lee DS, Johnson DE, Grandis JR. Interleukin 6 is increased in preclinical HNSCC models of acquired cetuximab resistance, but is not required for maintenance of resistance. PLoS One. 2020; 15(1):e0227261.  View on PubMed
  12. Lau YK, Ramaiyer M, Johnson DE, Grandis JR. Targeting STAT3 in Cancer with Nucleotide Therapeutics. Cancers (Basel). 2019 10 29; 11(11).  View on PubMed
  13. Hu L, Li H, Lee ED, Grandis JR, Bauman JE, Johnson DE. Gene targets of sulforaphane in head and neck squamous cell carcinoma. Mol Med Rep. 2019 Dec; 20(6):5335-5344.  View on PubMed
  14. Cai Y, Yousef A, Grandis JR, Johnson DE. NSAID therapy for PIK3CA-Altered colorectal, breast, and head and neck cancer. Adv Biol Regul. 2020 01; 75:100653.  View on PubMed
  15. Leonard BC, Lee ED, Bhola NE, Li H, Sogaard KK, Bakkenist CJ, Grandis JR, Johnson DE. ATR inhibition sensitizes HPV- and HPV+ head and neck squamous cell carcinoma to cisplatin. Oral Oncol. 2019 08; 95:35-42.  View on PubMed
  16. Sola AM, Johnson DE, Grandis JR. Investigational multitargeted kinase inhibitors in development for head and neck neoplasms. Expert Opin Investig Drugs. 2019 04; 28(4):351-363.  View on PubMed
  17. Hedberg ML, Peyser ND, Bauman JE, Gooding WE, Li H, Bhola NE, Zhu TR, Zeng Y, Brand TM, Kim MO, Jordan RCK, VandenBerg S, Olivas V, Bivona TG, Chiosea SI, Wang L, Mills GB, Johnson JT, Duvvuri U, Ferris RL, Ha P, Johnson DE, Grandis JR. Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer. J Exp Med. 2019 02 04; 216(2):419-427.  View on PubMed
  18. Galstyan A, Cho J, Johnson DE, Grandis JR. Modulation of the PI3K/mTOR pathways. In: Improving the therapeutic ratio in head and neck cancer. Editor: Randy Kimple. Elsevier. Pgs. 89-105. ISBN: 978-0-12-817868-3. 2019.  View on PubMed
  19. Lee YS, Johnson DE, Grandis JR. An update: emerging drugs to treat squamous cell carcinomas of the head and neck. Expert Opin Emerg Drugs. 2018 12; 23(4):283-299.  View on PubMed
  20. Njatcha C, Farooqui M, Kornberg A, Johnson DE, Grandis JR, Siegfried JM. STAT3 Cyclic Decoy Demonstrates Robust Antitumor Effects in Non-Small Cell Lung Cancer. . 2018 09; 17(9):1917-1926.  View on PubMed

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