Jill M. Siegfried, PhD
Professor of Pharmacology
Dr. Siegfried is a member of the Cellular and Molecular Pathology Graduate Training Program and the UPMC Endowed Chair for Lung Cancer Research.
Hillman Cancer Center
5117 Centre Avenue
Pittsburgh, PA 15232
Office Telephone: 412-623-7769
Lab Telephone: 412-623-7814
- MPhil - 1978, Yale University
- PhD - 1981, Yale University
Research InterestsDr. Siegfried investigates the role of growth factors and hormones in the development and growth of human lung cancer, with an emphasis on translation to the clinic. The laboratory focuses on the effects of these factors on control of tumor growth, their role in risk for cancer, and their signaling pathways. Growth factors and their receptors currently under investigation include estrogen and its receptors, epidermal growth factor receptor family and their ligands, gastrin-releasing peptide and its receptor, and hepatocyte growth factor and its receptor, c-Met.
Dr. Siegfried’s laboratory is interested in the role of ligands in determining receptor dependence in tumors, cross-talk between types of receptors, the role of estrogens in influencing tumor growth and growth factor secretion, and combined targeting of growth factor receptors for therapeutic benefit. These peptides are also being investigated as diagnostic or prognostic indicators for lung cancer. Hepatocyte growth factor has been found to be a strong negative prognostic indicator for non-small cell lung cancer, while expression of the gastrin-releasing pepide receptor in the human airway has been linked to increased lung cancer risk. These studies are directed toward development of new methods to identify high-risk individuals who may have early lung cancer and new chemotherapeutic or chemoprevention strategies through increased knowledge of genetic abnormalities and growth-regulatory processes in lung cancer cells.
These research efforts are being actively translated through Dr. Siegfried’s on-going multidisciplinary grant, Specialized Program of Research Excellence (SPORE) in Lung Cancer.
Awards and HonorsUPMC Endowed Chair for Lung Cancer Research
Selected PublicationsView Dr. Siegfried's publications on PubMed
Stabile LP, Rothstein ME, Keohavong P, Lenzner D, Land S, Gaither-Davis A, Kim KJ, Kaminski N, Siegfried JM. Targeting of both the c-Met and EGFR pathways results in additive inhibition of lung tumorigenesis in transgenic mice. Cancers 2010 2, 2153-70 doi: 10.3390/cancers2042153
Zeng X, Hood, BL, Sun M, Conrads TP, Day RS, Weissfeld JL, Siegfried JM, William L. Bigbee WL. Lung cancer serum biomarker discovery using glycoprotein capture and liquid chromatography mass spectrometry. J Proteome Res 2010 9(12):6440-9. PMID: 20931982.
Ostroff, R, Bigbee, WL, Franklin, W, Gold L, Mehan M, Miller Y, Pass HI, Rom W, Siegfried JM, Stewart A, Walker JR, Weissfeld, JL, Williams S, Zichi D, Brody E. Unlocking biomarker discovery: Large scale application of aptamer proteomic technology for early detection of lung cancer. PLos One 2010 5(12):e15003. PMCID: PMC2999620.
Siegfried JM. Early changes in pulmonary gene expression following tobacco exposure shed light on the role of estrogen metabolism in lung carcinogenesis. 2010 Cancer Prev Res 3:707-17. PMCID: PMC2881174.
Zeng X, Hood BL, Zhao T, Conrads TP, Sun M, Gopalakrishnan V, Grover H, Weissfeld JL, Wilson DO, Siegfried JM, Bigbee WL. Lung Cancer Serum Biomarker Discovery Using Label Free Liquid Chromatography Tandem Mass Spectrometry. 2011. J Thoracic Oncol. 6:725-734. PMCID: PMC3104087.
Stabile LP, Dacic S, Land SR, Lenzer D, Dhir R, Aquafondata M, Landreneau RJ, Grandis JR, Siegfried JM. Combined analysis of estrogen receptor beta-1 and progesterone receptor expression identifies lung cancer patients with poor outcome. 2011 Clin Cancer Res 17:154-64. PMCID: PMC3050630.
Dulak, A., Gubish, CT, Stabile, LP, Henry C, and Siegfried JM. HGF-Independent Potentiation of EGFR Action by c-Met. 2011 Oncogene 30(33):3625-35. PMCID: PMC3126872.
Keohavong P, Kahkonen B, Kinchington E, Yin J, Jin J, Liu X, Siegfried JM, Di YP. K-ras mutations in lung tumors from NNK-treated mice with lipopolysaccharide-elicited lung inflammation. 2011 Anticancer Res 31(9):2877-82. PMID: 21868532.
Wilson DO, Ryan A, Fuhrman C, Schuchert M, Shapiro S, Siegfried JM, Weissfeld J. Doubling times and CT screen detected lung cancers in the Pittsburgh Lung Screening Study (PLuSS). 2011 Am J. Respir Crit Care Med. PMCID: PMC3262038.
Buch SC, Diergaarde B, Nukui T, Day RS, Siegfried JM, Romkes M, Weissfeld JL. Genetic variability in DNA repair and cell cycle control pathway genes and risk of smoking-related lung cancer. 2011 Mol Carcinogenesis. PMCID: 3289753.
Xu H, Stabile LP, Gubish CT, Gooding WE, Grandis JR, Siegfried JM. Dual blockade of EGFR and c-Met abrogates redundant signaling and proliferation in head and neck carcinoma cells. 2011 Clin Cancer Res. 17(13):4425-38. PMCID: PMC3138116.
Bigbee WL, Gopalakrishnan V, Weissfeld JL, Wilson DO, Dacic S, Siegfried JM, Lokshin AE. A Multiplexed Serum Biomarker Immunoassay Panel Discriminates Clinical Lung Cancer Patients from High-Risk Individuals found to be Cancer-Free by CT Screening. 2012 J. Thoracic Oncol. PMCID: PMC3388353.
Siegfried JM, Gubish CT, Rothstein ME, Henry C, Stabile LP. Combining the multi-targeted tyrosine kinase inhibitor vandetanib with the antiestrogen fulvestrant enhances its antitumor effect in non-small cell lung cancer. J. Thorac Oncol. 2012. PMCID: PMC3288546.
Leng S, Stidley CA, Liu Y, Edlund CK, Willink RP, Han Y, Landi MT, Thun M, Picchi MA, Bruse SE, Crowell RE, Van Den Berg D, Caporaso NE, Amos CI, Siegfried JM, Tesfaigzi Y, Gilliland FD, Belinsky SA. Genetic determinants for promoter hypermethylation in the lungs of smokers: A candidate gene-based study. Cancer Res. 2012. PMCID: PMC3271143.
Pu J, Gu S, Liu S, Zhu S, Wilson DO, Siegfried JM, Gur D. CT based computerized identification and analysis of human airways: A review. Med Phys 2012, 30(5):2603-16. PMCID: PMC3344883.
Egloff AM, Liu X, Davis AL, Trevelline BK, Vuga M, Siegfried JM, Grandis JR. Elevated gastrin-releasing peptide receptor mRNA expression in buccal mucosa: Association with head and neck squamous cell carcinoma. Head Neck. 2012 Mar 20 [Epub ahead of print]. PMID: 22431275.
Wheeler S, Siwak DR, Chai R, Lavalle C, Seethala RR, Wang L, Cieply K, Sherer C, Joy C, Mills GC, Argiris, Siegfried JM, Grandis JR, Egloff AM. Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma. Clin Cancer Res. 2012 18(8):2278-89. PMID: 22351687.
Egloff AM, Gaither Davis A, Shuai Y, Land S, Pilewski JM, Luketich JD, Landreneau R, Miller YE, Grandis JR, Siegfried JM. Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case-control study. Respir Res. 2012 13:9. PMCID: PMC3305653.