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My lab is focused on investigating the extent to which local protein synthesis of specific mRNAs mediates the metastatic potential of normal epithelial cells. Cancer is a leading cause of death in the United States and represents a major public health problem. During the pathology of cancer, cells are thought to undergo a transition from normal epithelia to a more aggressive mesenchymal phenotype known as epithelial-mesenchymal transition (EMT). The mesenchymal cells are then able to leave the site of the primary tumor and colonize distance tissues in a process called metastasis. Ultimately it is the development of multiple metastases that finally overwhelms the immune system leading to death. The long term goal of the lab is to understand the molecular pathways that control EMT and metastasis to provide novel therapeutic approaches to treat cancer and prevent metastasis.
A key cellular hallmark of EMT is the loss of E-cadherin expression with a concomitant increase in N-cadherin expression. In addition, cells that have undergone EMT exhibit increased motility. Together these observations predict that cells that undergo EMT should have weaker cell-cell adhesion and increased motility. At the cellular level the actin cytoskeleton is a key player in both processes. In fact, during cell-contact formation the actin cytoskeleton makes linear actin cables which interact with the cadherin/catenin complex. By contrast, during motility the actin cytoskeleton makes branched actin arrays through an association with the Arp 2/3 complex. Thus understanding the pathways that mediate what types of actin filaments are formed in cell should provide insight into the process of EMT and metastasis. We are utilizing 4D-perfusion microscopy to perform live cell Ca2+ switch experiments to investigate how local synthesis of actin contributes to proper cell-cell contact formation in normal epithelia, cancer, and metastatic cells. We are utilizing FlAsH/ReAsH staining to determine where the actin mRNA is translated and where the newly synthesized protein is trafficked. Utilizing antisense oligonucleotides we will also delocalize actin translation in an attempt to drive normal epithelial into EMT.
B.A. in Biology, Yale University, 1994.
Ph.D. in Biology, Rutgers University, 2002.
Das, S., Yu, S., Sakamori, R., Vedula, P., Feng, Q., Flores, J., Hoffman, A., Fu, J., Stypulkowski, E., Rodriguez, A., Dobrowolski, R., Harada, A., Hsu, W., Bonder, E. M., Verzi, M. P., and Gao, N. (2015) Rab8a vesicles regulate Wnt ligand delivery and Paneth cell maturation at the intestinal stem cell niche. Development. 142:1-16. (DOI: 10.1242/dev.121046).
Gutierrez, N., Eromobor, I., Petrie, R., Vedula, P., Cruz, L., and Rodriguez, A. J. (2014) The β-actin mRNA zipcode regulates epithelial adherens junction assembly but not maintenance. RNA. 20:689-701. (DOI: 10.1261/rna.043208.113, PMID: 24681968).
Sakamori, R., Yu, S., Zhang, X., Sun, J., Das, S., Vedula, P., Li, G., Fu, J., Walker, G., Yang, C., Yi, Z., Hsu, W., Taketo, M., Rodriguez, A. J., Bonder, E. M., and Gao, N., (2014) CDC42 inhibition suppresses progression of incipient intestinal tumors. Cancer Research. (DOI: 10.1158/0008-5472.CAN-14-0267)
Rodriguez, A. J., Czaplinski, K., Condeelis, J., and Singer, R. H. (2008) Mechanisms and cellular roles of local protein synthesis in mammalian cells (Review). Trends Cell Biol. 20(2):144-149.
Rodriguez, A. J., Condeelis, J., Singer, R. H., and Dictenberg, J. (2007). Imaging mRNA movement from transcription to translation sites (Review). Semin Cell Dev Bio. 18(2):202-208.
Rodriguez, A. J., Shenoy, S. M., Singer, R. H., and Condeelis, J. (2006). Visualization of mRNA translation living cells. JCB. 175: 67-76.
Rodriguez, A. J., Hamill, D. R., Romancino, D. P., Seipel, S. A., Di Carlo, M., Suprenant, K. A., and Bonder, E. M. (2005). Sea urchin seawi – a member of the piwi/argonaute family is associated with MT-RNP complexes, binds ribosomes, and is developmentally regulated during embryogenesis. RNA. 11: 646-656.