About Dr. Johnson
The research in my laboratory is directed at defining the biological and molecular effects of the modulation of signal transduction pathways in lung, head and neck, and HPV+ cancers. We have defined novel mechanisms of sensitivity and resistance to kinase inhibitors. The three main projects are:
We recently discovered that head and neck squamous cell carcinoma (HNSCC) tumors harboring NOTCH1 mutations were more sensitive to drugs targeting the PI3K/mTOR pathway than HNSCC cell lines with wild-type NOTCH1 receptors. Goals of this project are to: Determine the efficacy of PI3K/mTOR pathway inhibition in HNSCC patients with tumors that harbor inactivating NOTCH1 mutations; Elucidate the molecular mechanism underlying PI3K/mTOR dependency and sensitivity to drugs targeting this pathway in NOTCH1 mutant HNSCC; and Identify therapeutic targets that work in combination with PI3K/mTOR inhibitors to prevent resistance and maximize killing of NOTCH1 mutant HNSCC.
We published the first large-scale, integrated analysis to determine mechanisms of polo-like kinase 1 (PLK1) inhibitor-induced apoptosis in NSCLC by assessing gene/protein expression, gene mutation, and PLK1 inhibitor sensitivity. Mesenchymal NSCLC cell lines were more sensitive to PLK1 inhibitors than epithelial NSCLC. Indeed, inducing an epithelial phenotype increased resistance and inducing a mesenchymal phenotype increased sensitivity. We are investigating candidate pathways that underlie sensitivity to PLK inhibition.
A recently completed screen of 1122 compounds in HPV+ cancer cell lines identified clinically-relevant Aurora kinase inhibitors as effective drugs. Integrated analysis of genomics, proteomics, gene expression, and drug sensitivity has identified several candidate pathways of resistance that are currently being studied.
Associate Professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
|1996||University of Texas Graduate School of Biomedical Sciences MD Anderson Cancer Center, Houston, TX, USA, PHD, Cancer Biology|
|1996||University of Texas Medical School at Houston, Houston, TX, USA, MD, Medicine|
|1989||The Johns Hopkins University, Baltimore, MD, USA, BA, Biology|
|2002-2003||Chief Medical Oncology Fellow, Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX|
|2000-2002||Clinical Fellowship, Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX|
|1997-2000||Clinical Residency, Internal Medicine, Baylor College of Medicine, Houston, TX|
- Ferrarotto R, Goonatilake R, Young Yoo S, Tong P, Giri U, Peng S, Minna J, Girard L, Wang Y, Wang L, Li L, Diao L, Peng DH, Gibbons DL, Glisson BS, Heymach JV, Wang J, Byers LA, Johnson FM. Epithelial-Mesenchymal Transition Predicts Polo-Like Kinase 1 Inhibitor-Mediated Apoptosis in Non-Small Cell Lung Cancer. Clin Cancer Res 22(7):1674-86, 2016. e-Pub 2015. PMID: 26597303.
- Saintigny P, Peng S, Zhang L, Sen B, Wistuba II, Lippman SM, Girard L, Minna JD, Heymach JV, Johnson FM. Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion. Mol Cancer Ther 11(9):2021-2032, 2012. e-Pub 2012. PMID: 22807579.
- Sen B, Peng S, Tang X, Erickson HS, Galindo H, Mazumdar T, Stewart DJ, Wistuba I, Johnson FM. Kinase-Impaired BRAF Mutations in Lung Cancer Confer Sensitivity to Dasatinib. Sci Transl Med 4(136):136ra70, 2012. PMID: 22649091.
- Sen B, Peng S, Woods DM, Wistuba I, Bell D, El-Naggar AK, Lai SY, Johnson FM. STAT5A-mediated SOCS2 expression regulates Jak2 and STAT3 activity following c-Src inhibition in head and neck squamous carcinoma. Clin Cancer Res 18(1):127-39, 2012. e-Pub 2011. PMID: 22090359.
- Sen B, Peng S, Saigal B, Williams MD, Johnson FM. Distinct interactions between c-Src and C-Met in mediating resistance to c-Src inhibition in head and neck Cancer. Clin Cancer Res 17(3):514-24, 2011. e-Pub 2010. PMID: 21106725.
- Johnson FM, Bekele BN, Feng L, Wistuba I, Tang XM, Tran HT, Erasmus JJ, Hwang LL, Takebe N, Blumenschein GR, Lippman SM, Stewart DJ. Phase II Study of Dasatinib in Patients with Advanced Non-Small Cell Lung Cancer. J Clin Oncol 28(30):4609-4615, 2010. e-Pub 2010. PMID: 20855820.
- Brannan JM, Sen B, Saigal B, Prudkin L, Behrens C, Solis L, Dong W, Bekele BN, Wistuba I, Johnson FM. EphA2 in the early pathogenesis and progression of non-small cell lung cancer. Cancer Prev Res (Phila) 2(12):1039-49, 2009. e-Pub 2009. PMID: 19934338.
- Byers LA, Sen B, Saigal B, Diao L, Wang J, Nanjundan M, Cascone T, Mills GB, Heymach JV, Johnson FM. Reciprocal regulation of c-Src and STAT3 in non-small cell lung cancer. Clin Cancer Res 15(22):6852-61, 2009. e-Pub 2009. PMID: 19861436.
- Johnson FM, Glisson BS. Chemotherapy: Irinotecan or etoposide as front-line therapy for SCLC?. Nat Rev Clin Oncol 6(10):562-3, 2009. PMID: 19786998.
- Brannan JM, Dong W, Prudkin L, Behrens C, Lotan R, Bekele BN, Wistuba I, Johnson FM. Expression of the Receptor Tyrosine Kinase EphA2 Is Increased in Smokers and Predicts Poor Survival in Non-Small Cell Lung Cancer. Clin Cancer Res 15(13):4423-30, 2009. e-Pub 2009. PMID: 19531623.
- Sen B, Saigal B, Parikh N, Gallick G, Johnson FM. Sustained Src inhibition results in signal transducer and activator of transcription 3 (STAT3) activation and cancer cell survival via altered Janus-activated kinase-STAT3 binding. Cancer Res 69(5):1958-65, 2009. e-Pub 2009. PMID: 19223541.
- Tsao AS, He D, Saigal B, Liu S, Lee JJ, Bakkannagari S, Ordonez NG, Hong WK, Wistuba I, Johnson FM. Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis, cell cycle arrest, and decreased migration and invasion. Mol Cancer Ther 6(7):1962-72, 2007. PMID: 17620427.
- Johnson FM, Saigal B, Tran H, Donato NJ. Abrogation of signal transducer and activator of transcription 3 reactivation after Src Kinase Inhibition results in Synergistic Antitumor Effects. Clin Cancer Res 13(14):4233-4244, 2007. PMID: 17634553.
- Mazumdar T, Byers LA, Ng PK, Mills GB, Peng S, Diao L, Fan YH, Stemke-Hale K, Heymach JV, Myers JN, Glisson BS, Johnson FM. A Comprehensive Evaluation of Biomarkers Predictive of Response to PI3K Inhibitors and of Resistance Mechanisms in Head and Neck Squamous Cell Carcinoma. Mol Cancer Ther. e-Pub 2014. PMID: 25193510.