The broad goal of our research is to delineate the molecular basis of human disease to identify novel treatment approaches.
One major focus of our studies is the characterization of the RIT1 oncoprotein, which is a key regulator of signal transduction pathways that control normal cell growth and differentiation. Using whole-exome sequence analysis on a subgroup of 'oncogene-negative' tumors allowed our recent identification of somatic RIT1 mutations in ~2.5% of lung adenocarcinoma cases. Importantly, RIT1 mutations were found to be mutually exclusive with all previously known driver mutations, and expression of mutant RIT1 induces cellular transformation. We are interested in further investigating the functional role of RIT1 in lung adenocarcinoma with the long-term goal of creating novel avenues for therapeutic intervention.
ProgramsMolecular and Cellular Oncology
- Oncogenic RIT1 mutations in lung adenocarcinoma.Berger, A.H., Imielinski, M., Duke, F., Wala, J., Kaplan, N., Shi, G.-X., Andres, D.A., and Meyerson, M. (2014) Oncogene 28:33(35):4418-23. PMID 24469055
- Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype.Koenighofer M, Hung CY, McCauley JL, Dallman J, Back EJ, Mihalek I, Gripp KW, Sol-Church K, Rusconi P, Zhang Z, Shi GX, Andres DA, Bodamer OA. (2015) Clin. Genet. 89(3): 359-66 PMID: 25959749
- A Rit GTPase-p38 Mitogen-Activated Protein Kinase Survival Pathway Confers Resistance to Cellular Stress.Shi, G-X., Jin, L., and Andres, D.A. (2011) Molecular and Cellular Biology 31(10), 1938-1948. PMID: 21444726 PMCID: PMC3133351
- Rit, a non-lipid-modified Ras-related protein, transforms NIH3T3 cells without activating the ERK, JNK, p38 MAPK or PI3K/Akt pathways.Rusyn, E.V., Reynolds, E.R., Shao, H., Grana T.M., Chan, T.O., Andres, D.A., and Cox, A.D. (2000) Oncogene. 19, 4685-4694.
- Rit subfamily small GTPases: Regulators in neuronal differentiation and survival.Shi, G-X, Cai, W., and Andres, D.A. (2013) Cell Signal. 25(10), 2060-2068. PMID 23770287