Research Summary

Dr. Jennifer R. Grandis received her medical degree from the University of Pittsburgh School of Medicine, Pennsylvania, and completed her internship from the same institution. Dr. Grandis completed both a residency and an Infectious Disease fellowship from the University of Pittsburgh School of Medicine, Pennsylvania. Prior to joining UCSF, Dr. Grandis was the UPMC Endowed Chair in Head and Neck Cancer Surgical Research and Distinguished Professor of Otolaryngology and Pharmacology and Chemical Biology at the University of Pittsburgh. She led the Head and Neck Cancer Program and was the Vice Chair for Research in the Department of Otolaryngology.

Dr. Grandis’s research focuses on the signal transduction in head and neck squamous cell carcinoma (HNSCC) development and progression with the ultimate goal of targeting key pathways for therapeutic benefit. By taking key findings from the clinic and investigating mechanisms in a series of preclinical models, as well as developing novel therapeutic approaches in the laboratory and carrying out innovative clinical trials that employ these treatment strategies.

Dr. Grandis is an American Cancer Society Clinical Research Professor, and a member of the American Society for Clinical Investigation, the American Association of Physicians and the Institute of Medicine of the National Academies. She has published over 260 peer-reviewed articles. She has also contributed to more than 50 review articles and book chapters.

Research:
Dr. Grandis's is dedicated to increasing our understanding of the genetic and epigenetic alterations in the upper aerodigestive tract mucosa, which mediate head and neck squamous cell carcinoma (HNSCC) progression. The overall goal is to identify predictive biomarkers, which can serve to select patients for therapies, including molecular targeting approaches. Translational resources developed to support projects include a large collection of patient-derived xenografts (PDXs) and tissue microarrays of over 500 human HNSCCs linked to a professionally curated clinical and pathologic database that includes information on treatment and survival. To date, the have examined the role of the epidermal growth factor receptor (EGFR), it’s ligands coordinate activation of STAT3 (signal transducer and activator of transcription) in head and neck carcinogenesis. Cumulative evidence from her laboratory suggests that TGF-?lpha/EGFR autocrine signaling leading to STAT3 activation is as early event in head and neck carcinogenesis. Strategies aimed at blocking the ligand, receptor or signaling protein demonstrated anti-tumor efficacy in preclinical models. Based on these promising results, they completed a Phase I clinical trial to investigate the toxicity and biologic effects of EGFR antisense gene therapy and a Phase II study was recently closed to accrual. They have developed STAT3 targeting strategies using a decoy oligonucleotide approach and early phase clinical testing demonstrated feasibility without toxicity. Ongoing studies are aimed at identifying the targetable genetic alterations in these cancers with the goal of designing precision medicine approaches. Emerging targets include activating mutations of the PI3K signaling pathway, primarily in HNSCC linked to HPV infection and mutation or promoter hypermethylation of selected PTPRs, which lead to STAT3 activation.

Specialty:
General Otolaryngology

Expertise:
Clinical and translational research

Professional Interests:
Head and neck cancer, signal transduction, precision medicine, experimental therapeutics, preclinical cancer models, receptor crosstalk

Education and Training:
• Medical School: University of Pittsburgh School of Medicine, Pittsburgh, PA
• Internship: University of Pittsburgh School of Medicine, Pittsburgh, PA
• Residency: University of Pittsburgh School of Medicine, Pittsburgh, PA
• Fellowship: University of Pittsburgh School of Medicine, Pittsburgh, PA – Infectious Disease

Research Funding

  • July 18, 2016 - June 30, 2026 - Clinical and Translational Science Institute , Principal Investigator . Sponsor: NIH, Sponsor Award ID: UL1TR001872
  • August 15, 2018 - July 31, 2025 - Integrating genomics and the protein interactome for HPV+ head and neck cancer therapy , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35CA231998
  • June 1, 1994 - June 30, 2025 - Postdoctoral Training in Head and Neck Oncology , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32CA060397
  • August 13, 2019 - May 31, 2024 - Targeting STAT3 to enhance anti-tumor immunity , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DE028289
  • May 1, 2014 - May 31, 2024 - PI3K Pathway Mutations in Head and Neck Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DE023685
  • July 1, 2002 - June 30, 2021 - Head and Neck Cancer SPORE , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: P50CA097190
  • August 1, 1988 - July 31, 2020 - Cancer Center Support Grant , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P30CA047904
  • December 1, 2002 - May 31, 2019 - GPCR Signaling in SCCHN: Integration with EGFR , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA098372
  • August 1, 1998 - May 31, 2019 - STAT Mediated TGF-a/EGFR Signaling in Squamous Cell Carcinomas of Head & Neck , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA077308
  • July 1, 2001 - June 30, 2018 - Research Training in Otolaryngology , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32DC000066
  • September 30, 2006 - June 30, 2016 - Clinical and Transtional Science Institute , Principal Investigator . Sponsor: NIH, Sponsor Award ID: KL2TR000143
  • September 30, 2006 - June 30, 2016 - Clinical and Transtional Science Institute , Principal Investigator . Sponsor: NIH, Sponsor Award ID: TL1TR000144
  • September 30, 2006 - June 30, 2016 - Clinical and Translational Science Institute , Principal Investigator . Sponsor: NIH, Sponsor Award ID: UL1TR000004
  • July 1, 2010 - June 30, 2011 - Research Workshop on the Biology, Prevention and Treatment of Head and Neck Cance , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13DE021296
  • August 1, 2004 - May 31, 2010 - Stat3 as a Therapeutic Target in Head and Neck Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA101840
  • December 1, 1978 - March 31, 2009 - General Clinical Research Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: M01RR000056
  • August 1, 1999 - July 31, 2006 - ORAL CANCER CENTER , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P60DE013059
  • July 1, 2005 - June 30, 2006 - Conf. on Research Education &Training in Otolaryngology , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13DC007325
  • July 1, 2003 - June 30, 2006 - Imaging of EGFR Targeting in Head and Neck Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA096815
  • September 30, 1996 - September 29, 1999 - TGF-ALPHA AND EGFR EXPRESSION IN HEAD AND NECK CANCER , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R03CA072526
  • July 1, 1993 - June 30, 1998 - AUTOCRINE GROWTH IN HEAD AND NECK CANCER , Principal Investigator . Sponsor: NIH, Sponsor Award ID: K11CA001760

Education

Swarthmore College, BA, Biology, 1982
Swarthmore College, BA, Art History, 1982
University of Pittsburgh, M.D., School of Medicine, 1987
University of Pittsburgh, Residency, School of Medicine, Surgery, 1988
University of Pittsburgh, Research Fellowship, School of Medicine, Infections Disease, 1992
University of Pittsburgh, Residency, School of Medicine, Otolaryngology, 1993

Honors & Awards

  • 2018
    Outstanding Investigator Award (R35 grant), National Cancer Institute
  • 2019
    William T. Butler Distinguished Lecturer, University of Texas Health Science Center at Houston School of Dentistry
  • 2019
    AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship, American Association for Cancer Research
  • 2019
    Dozor Visiting Scholar, Ben-Gurion University of the Negev
  • 2020
    Flexner Discovery Lecture, Vanderbilt University
  • 2022
    Elected Member, Fellows of the AACR Academy
  • 2023
    Mentoring Award, UCSF School of Medicine
  • 2023
    Long-Term Mentor Award, UCSF School of Medicine
  • 2023
    Mortel Visiting Professor Lectureship, Pennsylvania State University School of Medicine
  • 2023
    John Conley, MD Lecture on Medical Ethics, American Academy of Otolaryngology-Head and Neck Surgery Annual Meeting
  • 2024
    Joseph H. Ogura MD Annual Lecture, Triological Society

Selected Publications

  1. Nguyen JP, Na'ara S, Woerner LC, VanLandingham NK, Hoerner M, Santuray RT, Blum K, Kim MO, Johnson DE, Grandis JR. Blockade of the PGE2 pathway inhibits the growth of PTEN deficient HNSCC tumors. Mol Cancer Ther. 2025 Feb 20.  View on PubMed
  2. Fu BXH, Xu A, Li H, Johnson DE, Grandis JR, Gilbert LA. Loss of Fanconi anemia proteins causes a reliance on lysosomal exocytosis. bioRxiv. 2025 Jan 24.  View on PubMed
  3. Gencel-Augusto J, Minaya NJ, Johnson DE, Grandis JR. Underrepresentation of Hispanic women in science, technology, engineering, mathematics, and medicine. CA Cancer J Clin. 2025 Jan 09.  View on PubMed
  4. Callander JK, Johnson DE, Grandis JR. Social capital as a catalyst for gender inequality: A scoping review of networking disparities in academic medicine. Cancer. 2025 Jan 01; 131(1):e35667.  View on PubMed
  5. Nguyen JP, Woerner LC, Johnson DE, Grandis JR. Future investigative directions for novel therapeutic targets in head and neck cancer. Expert Rev Anticancer Ther. 2024 Nov; 24(11):1067-1084.  View on PubMed
  6. Cui Z, Kang H, Li H, Lee ED, Lee YS, Peterson CN, Long SR, Grandis JR, Johnson DE. CYLD Alterations Are Associated With Metastasis and Poor Prognosis in Human Papilloma Virus-Positive Head and Neck Cancer. Head Neck. 2025 Feb; 47(2):606-614.  View on PubMed
  7. Steinman RA, Gandy LM, Qi H, Fertig EJ, Blackford AL, Grandis JR. Career trajectories of MD-PhD physician scientists: The loss of women investigators. Cancer Cell. 2024 May 13; 42(5):723-726.  View on PubMed
  8. Qin B, Chen X, Zhu J, Kopechek J, Helfield B, Yu F, Cyriac J, Lavery L, Grandis JR, Villanueva FS. Ultrasound enhanced siRNA delivery using cationic liposome-microbubble complexes for the treatment of squamous cell carcinoma. Nanotheranostics. 2024; 8(3):285-297.  View on PubMed
  9. Chung DH, Kong S, Young NJ, Chuo SW, Shiah JV, Connelly EJ, Rohweder PJ, Born A, Manglik A, Grandis JR, Johnson DE, Craik CS. Rare antibody phage isolation and discrimination (RAPID) biopanning enables identification of high-affinity antibodies against challenging targets. Commun Biol. 2023 10 12; 6(1):1036.  View on PubMed
  10. Lee RH, Johnson DE, Grandis JR. To Tip or Not to Tip: A New Combination for Precision Medicine in Head and Neck Cancer. Cancer Res. 2023 10 02; 83(19):3162-3164.  View on PubMed
  11. Jagadeeshan S, Novoplansky OZ, Cohen O, Kurth I, Hess J, Rosenberg AJ, Grandis JR, Elkabets M. New insights into RAS in head and neck cancer. Biochim Biophys Acta Rev Cancer. 2023 11; 1878(6):188963.  View on PubMed
  12. Jagadeeshan S, Prasad M, Badarni M, Ben-Lulu T, Liju VB, Mathukkada S, Saunders C, Shnerb AB, Zorea J, Yegodayev KM, Wainer M, Vtorov L, Allon I, Cohen O, Gausdal G, Friedmann-Morvinski D, Cheong SC, Ho AL, Rosenberg AJ, Kessler L, Burrows F, Kong D, Grandis JR, Gutkind JS, Elkabets M. Mutated HRAS Activates YAP1-AXL Signaling to Drive Metastasis of Head and Neck Cancer. Cancer Res. 2023 04 04; 83(7):1031-1047.  View on PubMed
  13. Lee RH, Roy R, Li H, Hechmer A, Zhu TR, Izgutdina A, Olshen AB, Johnson DE, Grandis JR. Therapeutic implications of transcriptomics in head and neck cancer patient-derived xenografts. PLoS One. 2023; 18(3):e0282177.  View on PubMed
  14. Mascarella MA, Olonisakin TF, Rumde P, Vendra V, Nance MA, Kim S, Kubik MW, Sridharan SS, Ferris RL, Fenton MJ, Clayburgh DR, Ohr JP, Joyce SC, Sen M, Herman JG, Grandis JR, Zandberg DP, Duvvuri U. Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit. Clin Cancer Res. 2023 02 16; 29(4):723-730.  View on PubMed
  15. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Author Correction: Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2023 Jan 19; 9(1):4.  View on PubMed
  16. Shiah JV, Johnson DE, Grandis JR. Transcription Factors and Cancer: Approaches to Targeting. Cancer J. 2023 Jan-Feb 01; 29(1):38-46.  View on PubMed
  17. VanLandingham NK, Nazarenko A, Grandis JR, Johnson DE. The mutational profiles and corresponding therapeutic implications of PI3K mutations in cancer. Adv Biol Regul. 2023 01; 87:100934.  View on PubMed
  18. Qureshy Z, Li H, Zeng Y, Rivera J, Cheng N, Peterson CN, Kim MO, Ryan WR, Ha PK, Bauman JE, Wang SJ, Long SR, Johnson DE, Grandis JR. STAT3 Activation as a Predictive Biomarker for Ruxolitinib Response in Head and Neck Cancer. Clin Cancer Res. 2022 11 01; 28(21):4737-4746.  View on PubMed
  19. Long Z, Grandis JR, Johnson DE. Emerging tyrosine kinase inhibitors for head and neck cancer. Expert Opin Emerg Drugs. 2022 09; 27(3):333-344.  View on PubMed
  20. Brand TM, Hartmann S, Bhola NE, Li H, Zeng Y, O'Keefe RA, Ranall MV, Bandyopadhyay S, Soucheray M, Krogan NJ, Kemp C, Duvvuri U, LaVallee T, Johnson DE, Ozbun MA, Bauman JE, Grandis JR. Correction: Cross-talk Signaling between HER3 and HPV16 E6 and E7 Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer. Cancer Res. 2022 Sep 02; 82(17):3187.  View on PubMed

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