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Jennifer Grandis, MD
Distinguished Professor, Otolaryngology, Asst VC for Research Integration
Suite 500 Eye and Ear Institute Building
Pittsburgh, PA 15213

Email:
jgrandis@pitt.edu
Phone: 412-647-5280

Fax: 412-647-2080


Education

BA (Biology and Art History), Swarthmore College, 1982.
MD, University of Pittsburgh School of Medicine, 1987.
Internship, Department of Surgery, University of Pittsburgh School of Medicine, 1987-88.
Residency, Department of Otolaryngology, University of Pittsburgh School of Medicine, 1988-93.
Research Fellow, Department of Medicine, Division of Infectious Disease, University of Pittsburgh, School of Medicine, 1991-9.



Research Areas
Cancer Pharmacology
Photo of Jennifer Grandis, MD

Dr. Rubin Grandis’ research program is dedicated to increasing our understanding of the genetic alterations in the upper aerodigestive tract mucosa, which result in head and neck squamous cell carcinoma. The overall goal is to identify pathways that can serve as therapeutic targets for novel preventive or treatment strategies. We are studying signaling pathways regulated by the epidermal growth factor receptor (EGFR), stimulated by direct activation (EGFR ligand) and indirect activation (G-protein-coupled receptor ligand). Cumulative evidence from our lab today suggests that EGFR autocrine signaling is activated early in head and neck carcinogenesis where expression levels of ligand or receptor are important prognostic indicators in head and neck cancer patients. Strategies aimed at blocking the ligand or receptor demonstrated anti-tumor efficacy in preclinical models and in a phase I clinical trial to investigate the toxicity and biologic effects of EGFR antisense gene therapy.

 

Other studies are aimed at elucidating the molecular mechanisms underlying the EGFR autocrine regulatory pathway. This work has demonstrated mitogenic signaling as a result of EGFR-mediated activation of selective STAT proteins including STAT3. Current projects are investigating strategies to block activated STAT3 including a transcription factor decoy, which has completed early phase clinical testing and a small molecule inhibitors that have emerged from a high content drug screening effort. In summary, our translation research efforts are dedicated to elucidating the critical growth pathways in head and neck cancer progression. By characterizing cell lines and patient tissues, followed by examination of mitogenic signaling mechanisms in preclinical animal models, we hope to develop innovative approaches to preventing and treating this frequently fatal malignancy.







Important Publications
Lui VW, Hedberg ML, Li H, Vangara B, Pendleton K, Zeng Y, Lu Y, Zhang Q, Du Y, Gilbert B, Freilino M, Sauerwein S, Peyser N, Xiao D, Diergaarde B, Wang L, Chiosea S, Seethala RR, Johnson JT, Kim S, Duvvuri U, Ferris RL, Romkes M, Nukui T, Ng P, Garraway L, Hammerman P, Mills GB, Grandis JR. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discovery. Epub 2013 Apr 26. PMID: 23619167. PMCID: PMC Journal-in-process.
Quesnelle KM, Wheeler SA, Ratay M, Grandis JR. Preclinical modeling of EGFR inhibitor resistance in head and neck cancer. Cancer Biology & Therapy. 2012 Aug; 13(10): 1-11. PMID:22785204. PMCID: PMC3414414 [Available 2013/8/1].
Sen M, Thomas SM, Kim SW, Yeh JI, Ferris RL, Jonhson JT, Duvvuri U, Lee JA, Sahu N, Joyce S, Freilino ML, Shi H, Li C, Ly D, Rapireddy S, Etter JP, Li PK, Wang L, Chiosea S, Seethala RR, Gooding WE, Chen X, Kaminski N, Pandit K, Johnson DE, Grandis JR. First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discovery. 2012 Aug; 2(8): 694-705. Doi: 10.1158/2159-8290.CD-12-0191. Epub 2012 Jun 20. PMID: 22719020. NIHMSID: 468365. PMC Journal-in process.
Bhola N, Freilino M, Joyce SC, Sen M, Thomas SM, Sahu A, Cassell A, Chen CS, Grandis JR. Anti-tumor mechanisms of targeting the PDK1 pathway in head and neck cancer. Molecular Cancer Therapeutics. 2012 Jun; 11(6): 1236-46. Epub 2012 Apr 5. PMID: 22491800. PMCID: PMC3413198 [Available on 2013/6/1].
Stransky N, Egloff AM, Tward A, Kostic A, Cibulskis K, Sivachenko A, Kryukov G, Lawrence M, Sougnez C, McKenna A, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes M, Auclair D, Saksena G, Guiducci C, Onofrio R, Parkin M, Romkes M, Weissfeld J, Seethala RR, Wang L, Winckler W, Ardlie K, Gabriel SB, Myerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011 Aug 26;333(6046): 1157-60. Epub 2011 Jul 28. PMID: 21798893. PMCID: PMC3415217.
Lui VWY, A Boehm, P Koppikar, R Leeman, D Johnson, M Ogagan, E Childs, M Freilino and JR Grandis. Antiproliferative mechanisms of a transcription factor decoy targeting STAT3: The role of STAT1. Molecular Pharmacology 71(5):1435-1443, 2007.
Zhang Q, NE Bhola, VWY Lui, DR Siwak, S Xi, SM Thomas, CT Gubish, JM Siegfried, GB Mills and JR Grandis. Antitumor mechanisms of combined GRPR and EGFR targeting in head and neck Cancer. Molecular Cancer Therapeutics 6(4):1414-1424, 2007.
Thomas SM, N Bhola, Q Zhang, AL Wentzel, M Freilino, WE Gooding, JM Siegfried, DC Chan and JR Grandis. Cross-talk between G-protein-coupled receptor and epidermal growth factor receptor signaling pathways contributes to growth and invasion of head and neck squamous cell carcinoma. Cancer Research 66(24):11831-11839, 2006.
Zhang Q, SM Thomas, VWY Lui, S Xi, JM Siegfried, H Fan, T Smithgall, G Mills and JR Grandis. Phosphorylation of TNF-a converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation. Proc National Acad Sci 103:6901-6906, 2006.
Xi S, KF Dyer, M Kimak, Q Zhang, WE Gooding, JR Chaillet, RL Chai, RE Ferrell, B Zamboni, J Hunt and JR Grandis. Decreased STAT1 expression by promoter methylation in squamous cell carcinogenesis. J National Cancer Institute 98:181-189, 2006.




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