
I am a Research Technician IV in the School of Medicine at the University of Pittsburgh. During my more than 30 years at the university, I have contributed to many research projects in the areas of immunohistochemistry, targeted therapeutics, cell signaling pathways including the role of hormones and growth factors in lung cancer and head and neck cancer, cell line development, processing of human biospecimens and tissue culture. I also have developed and continually maintain several clinical databases for IRB-approved clinical trials. My work has assisted many researchers, both internal and external, resulting in 16 peer reviewed publications. I am certain that I have the expertise, training, and motivation necessary to successfully carry out my portion of the proposed research project.
Contributions to Science
1. My work has assisted in demonstrating that signaling pathways including the estrogen signaling pathway,
hepatocyte growth factor (HGF)/MET, and epidermal growth factor receptor (EGFR) pathways play a
biological role in non-small cell lung cancer.
a. Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD, Christie N, Finkelstein S, Siegfried JM. Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res. 2002 Apr 1;62(7):2141-50. PMID: 11929836.
b. Stabile LP, Rothstein ME, Keohavong P, Lenzner D, Land SR, Gaither-Davis AL, 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 (Basel). 2010 Dec 1;2(4):2153-70. PMID: 21390244; PMCID: PMC3049550.
c. Pilewski JM, Bumbalo TS 3rd, Davis AG, Siegfried JM. Hepatocyte growth factor promotes tumor growth in a novel in vivo model of human lung cancer. Am J Respir Cell Mol Biol. 2001 May;24(5):556-62. PMID: 11350824.
2. I have assisted in clinical processing and biomarker analysis in early phase clinical testing of targeted
treatments in head and neck squamous cell carcinoma and lung cancer.
a. Bauman JE, Ohr J, Gooding WE, Ferris RL, Duvvuri U, Kim S, Johnson JT, Soloff AC, Wallweber G, Winslow J, Gaither-Davis A, Grandis JR, Stabile LP. Phase I study of ficlatuzumab and cetuximab in cetuximab-resistant, recurrent/metastatic head and neck cancer. Cancers. 2020 June 11; 12(6):1537.PMID: 32545260.
b. Espinosa-Cotton M, Fertig EJ, Stabile LP, Gaither-Davis A, Bauman JE, Schmitz S, Gibson-Corley KN, Cheng Y, Jensen IJ, Badovinac VP, Laux D, Simons AL. A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab. Biomark Res. 2019 Jul 16;7:14. PMID: 31346466; PMCID: PMC6636109.
c. Tarhini AA, Rafique I, Floros T, Tran P, Gooding WE, Villaruz LC, Burns TF, Friedland DM, Petro DP, Farooqui M, Gomez-Garcia J, Gaither-Davis A, Dacic S, Argiris A, Socinski MA, Stabile LP, Siegfried JM. Phase 1/2 study of rilotumumab (AMG 102), a hepatocyte growth factor inhibitor, and erlotinib in patients with advanced non-small cell lung cancer. Cancer. 2017 Aug 1;123(15):2936-2944. PMID: 28472537; PMCID: PMC5517339.
d. Yoneyama T, Gorry M, Sobo-Vujanovic A, Lin Y, Vujanovic L, Gaither-Davis A, Moss ML, Miller MA, Griffith LG, Lauffenburger DA, Stabile LP, Herman J, Vujanovic NL. ADAM10 Sheddase Activity is a Potential Lung-Cancer Biomarker. J Cancer. 2018 Jun 23;9(14):2559-2570. PMID: 30026855; PMCID: PMC6036891.
e. Gao W, Jin J, Yin J, Land S, Gaither-Davis A, Christie N, Luketich JD, Siegfried JM, Keohavong P. KRAS and TP53 mutations in bronchoscopy samples from former lung cancer patients. Mol Carcinog. 2017 Feb;56(2):381-388. PMID: 27182622.
3. My work assisted in demonstrating that the expression of gastrin releasing peptide receptor (GRPR) is a risk factor for lung cancer. We also showed that GRPR stimulates lung cancer cell proliferation and is more active in women than in men.
a. Siegfried JM, DeMichele MA, Hunt JD, Gaither Davis A, Vohra K, Pilewski J. Expression of mRNA for gastrin-releasing peptide receptor by human bronchial epithelial cells. Association with prolonged tobacco exposure and responsiveness to bombesin-like peptides. American journal of respiratory and critical care medicine. 1997. 156: 358-366. [SLP(2]
b. Siegfried JM, Krishnamachary N, Gaither Davis A, Gubish C, Hunt JD, Shriver SP. Evidence for autocrine actions of neuromedin B and gastrin-releasing peptide in non-small cell lung cancer.Pulm Pharmacol Ther. 1999;12(5):291-302. PMID: 10545285
c. Liu X, Carlisle DL, Swick MC, Gaither-Davis A, Grandis JR, Siegfried JM. Gastrin-releasing peptide activates Akt through the epidermal growth factor receptor pathway and abrogates the effect of gefitinib. Exp Cell Res. 2007 Apr 15;313(7):1361-72. PMID: 17349623
d. 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 Feb 1;13(1):9. PMID: 22296774; PMCID: PMC3305653
e. Shriver SP, Bourdeau HA, Gubish CT, Tirpak DL, Davis AL, Luketich JD, Siegfried JM. Sex-specific expression of gastrin-releasing peptide receptor: relationship to smoking history and risk of lung cancer. J Natl Cancer Inst. 2000 Jan 5;92(1):24-33. PMID: 10620630.
4. I have assisted in clinical processing and biomarker analysis to aid in early detection and risk
susceptibility of lung cancer.
a. Ostrow KL, Hoque MO, Loyo M, Brait M, Greenberg A, Siegfried JM, Grandis JR, Gaither Davis A, Bigbee WL, Rom W, Sidransky D. Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR. Clin Cancer Res. 2010 Jul 1;16(13):3463-72. PMID: 20592015; PMCID: PMC2899894
b. Buch S, Zhu B, Davis AG, Odom D, Siegfried JM, Grandis JR, Romkes M. Association of polymorphisms in the cyclin D1 and XPD genes and susceptibility to cancers of the upper aero-digestive tract. Mol Carcinog. 2005 Apr;42(4):222-8. PMID: 15754315.
c. Leng S, Liu Y, Weissfeld JL, Thomas CL, Han Y, Picchi MA, Edlund CK, Willink RP, Gaither Davis AL, Do KC, Nukui T, Zhang X, Burki EA, Van Den Berg D, Romkes M, Gauderman WJ, Crowell RE, Tesfaigzi Y, Stidley CA, Amos CI, Siegfried JM, Gilliland FD, Belinsky SA. 15q12 variants, sputum gene promoter hypermethylation, and lung cancer risk: a GWAS in smokers. J Natl Cancer Inst. 2015 Feb 23;107(5). PMID: 25713168; PMCID: PMC4555640.