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Grandis_Jennifer_MD_4-2008_Otolaryngology Jennifer R. Grandis

Vice Chair for Research
Professor of Otolaryngology & Pharmacology
University of Pittsburgh School of Medicine
Program Leader, Head & Neck Cancer Program
University of Pittsburgh Cancer Institute
MD, FACS
Eye and Ear Institute, Suite 500
200 Lothrop St.
Pittsburgh, PA 15213
Phone: 412-647-2100
Email: jgrandis@pitt.edu
Fax: 412-383-5409; 412-647-2080
 
Research Interests
Dr. Grandis’ current research efforts include the following:

1. Src Family Kinase Inhibitors- Src Family Kinase Inhibitors (e.g. dasatinib) are being tested in ongoing and planned clinical trials at UPCI in head and neck cancer patients. Ongoing projects in the lab are testing the hypothesis that activation of Src family kinases through both EGFR dependent and EGFR independent pathways contributes to SCCHN progression in the setting of EGFR blockade.
2. STAT3 as a Therapeutic Target- Evidence to date suggests that activation of Signal Transducer and Activator of Transcription 3 (STAT3) contributes to tumor growth, even in the setting of EGFR blockade. Ongoing studies are testing the hypothesis that STAT3 activation enhances SCCHN growth and contributes to resistance to therapies that target EGFR. New efforts are designed to use high throughput screens to identify small molecule inhibitors of STAT3. A STAT3 decoy oligonucleotide is also being designed as a therapeutic strategy.
3. EGFRvIII as a Therapeutic Target and Mediator of Clinical Resistance- The only alteration to date of EGFR identified in SCCHN tumors is the deletion variant, EGFRvIII, which mediates resistance to cetuximab by signaling through STAT3. Ongoing studies are testing the role of Src kinases in EGFRvIII signaling in SCCHN and developing a heterotopic xenograft model of EGFRvIII expressing tumors to test therapies.
4. Combined Molecular Targeting Approaches for SCCHN- Inhibition of a single pathway alone is unlikely to be beneficial for cancer treatment. We have access to a large number of small molecule inhibitors of critical signaling pathways that are in active clinical development. Ongoing studies are testing the effects of combining these inhibitors with anti-EGFR agents in preclinical SCCHN models to design rational therapeutic approaches.
 
Publications
Grandis JR, Zeng Q, Tweardy DJ. Retinoic acid normalized the increased gene transcription rate of TGF-alpha and EGFR in head and neck cancer cell lines. Nature Medicine, 2:237-240, 1996.

Grandis JR, Drenning SD, Zeng Q, Zeng Q, Watkins SF, Melhem MF, Endo S, Johnson DE, Huang L, Kim JD. Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo. Proc Natl Acad Sci, USA 97(8):4227-32, 2000.

Leong, PL, Andrews GAA, Johnson DE, Dyer KF, Xi S, Mai JC, Robbins PD, Gadiparthi S, Burke NA, Watkins SF, Grandis JR. Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc National Acad Sci. 100(7) 4138-4143, 2003.

Zhang Q, Thomas SM, Lui VWY, Xi S, Siegfried JM, Fan H, Smithgall T, Mills G, Grandis JR. Phosphorylation of TNF-alpha converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation. Proc National Acad Sci. 103: 6901-6906, 2006.
 
Academic Affiliation
1. Otolaryngology (Vice Chair for Research)
2. UPCI (Co-Director, Head and Neck Cancer Program)
 
Education
1978 -1982 Swarthmore College, BA

1983-1987 University of Pittsburgh School of Medicine, MD

Post Graduate
1987-1988 Department of Surgery
University of Pittsburgh School of Medicine

1988-1993 Department of Otolaryngology University of Pittsburgh School of Medicine

1991-1992 Research Fellow, Department of Medicince Division of Infectious Disease
University of Pittsburgh School of Medicine



 
Grants
Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer, Principle Investigator

Chemoprevention of Head and Neck Cancer with ZD1839 and Celecoxib for Former Smokers, Co-Investigator

Research Training in Otolaryngology, Principle Investigator

STAT Mediated TGF-EGFR signaling in SCCHN, Principle Investigator

Postdoctoral research Training in Head & Neck Oncology, Principle Investigator

Cancer Center Support Grant, Program Leader

GRPR Signaling in SCCHN: Integration with EGFR, Principle Investigator

STAT3 as a Therapeutic Target in Head and Neck Cancer, Principle Investigator

Postdoctoral Research Training in Head and Neck Oncology, Principle Investigator

Design of a New Clinical Research Training Program, Co-Investigator

OSI Pharmaceuticals Cancer Modulation of Biomarkers to Predict Clinical Response to Administration of Neoadjuvant Tarceva Plus Sulindac and Adjuvant Tarceva for Head and Neck, Principle Investigator

Research Supplement to Promote Diversity in Health Related Research SPORE Minority Supplement, Principle Investigator

SPORE Supplement – Combined EGFR & VEGF Inhibition for Treatment of Head & Neck Cancer, Principle Investigator

SPORE in Lung Cancer, Co-Project Leader

NIH Mentored clinical Scientist Development Award (K08) Regulation of Invasion and Metastasis by HIF-1 in Oral Squamous Cell Carcinoma, Mentor

Prevention of head and Neck carcinogenesis with a plant-derived compound, Mentor
 
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