Jennifer Rubin Grandis, Associate Professor
M.D., University of Pittsburgh School of Medicine, 1987
Director of the Head and Neck Cancer Program
Email: jgrandis@pitt.edu
Area of Interest:
Investigating the role of TGF- /EGFR autocrine signaling in head and neck carcinogenesis and the development of preventative and therapeutic strategies that interfere with EGFR signaling pathways. EGFR activation mechanisms and integration with G-protein-coupled receptor signaling
Research:
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 TGF- /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. Based on these promising results, we have initiated a Phase I clinical trial to investigate the toxicity and biologic effects of EGFR antisense gene therapy. Further studies are aimed at elucidating the molecular mechanisms underlying the TGF- /EGFR autocrine regulatory pathway. These studies have demonstrated mitogenic signaling as a result of EGFR-mediated activation of selective STAT proteins including Stat3 and Stat5b in head and neck cancer cells. Current projects are investigating strategies to block activated Stat3 and/or Stat5b for potential use as cancer therapy. 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.
Recent Publication
Lin CJ, Grandis JR, Carey TE, Gollin SM, Whiteside TL, Ferris RL, Lai SY. Head and Neck Squamous Cell Carcinoma Cell Lines: Established Models and Rationale for Selection. Head &Neck. 29, 163-88, 2007.
Fridman JS, Caulder E, Hansbury M, Liu X, Yang G, Wang Q, Lo Y, Zhou B, Thomas SM, Grandis JR, Zhuo J, Yao W, Newton RC, Friedman SM, Scherle PA, Vaddi K. Selective inhibition of ADAM metalloproteases as a novel approach for modulating ErbB pathways in cancer. Clinical Cancer Research, 13(6):1892-902, 2007.
Nelson A, Grandis JR. The role of CD44 in HNSCC. Cancer Biology & Therapy, Jan 24;6(1) 125-126, 2007.
Zhang W, Weissfeld JL, Romkes M, Land SR, Grandis JR and Siegfried JM. Association of the EGFR Intron 1 CA Repeat Length with Lung Cancer Risk. Molecular Carcinogenesis. 46(5): 372-80, 2007.
Zhang Q, Bhola NE, Lui VWY, Siwak DR, Xi S, Thomas SM, Gubish CT, Siegfried, Mills GB, Grandis JR. Antitumor mechanisms of combined GRPR and EGFR targeting in head and neck Cancer. Molecular Cancer Therapeutics, 6(4):1414-24, 2007.
Lui VWY, Boehm A, Koppikar P, Leeman R, Johnson D, Ogagan M, Childs E, Freilino M, Grandis JR. Antiproliferative Mechanisms of a Transcription Factor Decoy Targeting STAT3: the Role of STAT1. Molecular Pharmacology, 71(5): 1435-43, 2007.
Siegfried JM, Grandis JR, Bigbee W. The Biology Behind: Multiple cytokine and growth factor serum biomarkers predict therapeutic response and survival in advanced-stage head and neck cancer patients. Clinical Cancer Research, 13(11): p. 3107-8, 2007.
Karamouzis M, Grandis JR, Argiris A. Therapies directed against epidermal growth factor receptor in aerodigestive carcinomas. 298(1): 70-82, JAMA, 2007.
Moore, BA, Albers KM, Davis BM, Grandis JR, T?gel S, Bauer AJ. Altered Inflammatory Gene Expression Underlies Iincreased Susceptibility to Murine Postoperative Ileus with Advancing Age. AJP: GI and Liver Physiology, 292(6): G1650-9, 2007.
Quesnelle K, Boehm AL, Grandis JR STAT-mediated EGFR signaling in cancer. Journal Cellular Biochemistry. 2007 Jul 27; [Epub ahead of print].
Bigbee WL, Grandis JR, Siegfried JM. Multiple Cytokine and Growth Factor Serum Biomarkers Predict Therapeutic Response and Survival in Advanced-Stage Head and Neck Cancer Patients. Clinical Cancer Research, 13, 3107-3108, 2007.
Grandis JR, Carbone DP, Rustgi AK. Advances and Challenges in Aerodigestive Epithelial Cancer: Meeting Summary and Research Opportunities. American Association for Cancer Research, 67(16): 7556-7558.
Kim S, Grandis JR. Targeting the Epidermal Growth Factor Receptor in Head and Neck Cancer: Emerging Issues. In Press, Touch Briefings, 2007.
Grandis JR. Established and Emerging Concepts in EGFR Biology. In Press, International Journal of Radiation Oncology, Biology, Physics, 2007.
Ferris RL, Grandis JR. NF-?B Gene Signatures and p53 Mutation in Head and Neck Squamous Cell Carcinoma. In Press, Clinical Cancer Research, 2007.
Karamouzis, MV, Argiris A, Grandis JR. Clinical Applications of Gene Therapy in Head and Neck Cancer. In Press, Current Gene Therapy, 2007.
Bhola NE, Grandis JR. Crosstalk between G-protein-coupled receptors and Epidermal growth factor receptor in cancer. In Press, Frontiers in Bioscience, 2007.
Li R, Boehm AL, Miranda MB, Shangary S, Grandis JR, Johnson DE. Targeting Antiapoptotic Bcl-2 Family Members with Cell-Permeable BH3 Peptides Induces Apoptosis Signaling and Death in Head and Neck Squamous Cell Carcinoma Cells. In Press, Neoplasia, 2007.
Argiris A, Karamouzis MV, Johnson J, Heron DE, Myers E, Eibling D, Cano E, Urba S, Gluckman J, Grandis JR, Wang Y, Agarwala SS. Long-term results of a phase III randomized trial of postoperative radiotherapy with or without carboplatin in patients with high-risk head and neck cancer. In Press, Laryngoscope, 2007
Zhang Q, Thomas SM, Lui VWY, Xi S, Siegfried JM, Fan H, Smithgall T, Mills G, Grandis JR. Phosphorylation of TNF- converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation. Proc National Acad Sci. 103: 6901-6906, 2006.
Zhou W, Grandis JR, Wells A. STAT3 is required but not sufficient for EGF receptor-mediated migration and invasion of human prostate carcinoma cell lines. British Journal of Cancer, 95:164 - 171, 2006.
Egloff AM, Grandis JR. Epidermal growth factor receptor targeted molecular therapeutics for head & neck squamous cell carcinoma. Expert Opinion Therapeutc Targets, 10(5):639-47, 2006.
Sok J, Coppelli FM, Thomas SM, Lango MN, Xi S, Hunt JL, Freilino ML, Graner MW, Wikstrand CJ, Bigner DD, Gooding WE, Furnari FB, Grandis JR. Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting. Clinical Cancer Research, 12(17):5064-5073, 2006.
Grandis, JR. Prognosic Biomarkers in Head & Neck Cancer. Clinical Cancer Research, 12(17), 5005-5006, 2006.
Voynov G, Burton S, Gerszten PC, Ozhasoglu C, Vogel W, Quinn A, Johnson JT, Grandis J, Ferris R, Heron DE. Frameless stereotactic radiosurgery for recurrent squamous cell carcinoma of the head and neck region. Technology in Cancer Research and Treatment, 529-536, 2006.
Zhang W, Stabile LP, Keohavong P, Romkes M, Grandis JR, Traynor AM, Siegfried JM. Mutation and Polymorphism in the EGFR-TK Domain Associated with Lung Cancer. J. Thoracic Oncol. 1(7): 635-647, 2006.
Lai SY, Grandis JR: Understanding the Presence and Function of Erythropoietin Receptors on Cancer Cells. JCO. 24(29):4675-4676, 2006.
Thomas SM, Bhola N, Zhang Q, Wentzel AL, Freilino M, Gooding WE, Siegfried JM, Chan DC, Grandis JR. 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.
