The Cerione group is studying signaling pathways that are important in various biological outcomes, with particular emphasis on cancer progression and neurogenesis. They are using a combination of biochemical, structural, genetic, and small molecule chemistry to probe these pathways.
ResearchThe research efforts of my laboratory have focused on understanding how cellular signaling pathways influence cell growth and differentiation, as well as how aberrant signaling activities lead to disease states such as cancer and other disorders. The laboratory is multi-disciplinary using various cell systems and mouse models to identify novel signaling events that influence fundamentally important biological processes, and chemistry and structural approaches to define the molecular basis for these events. Three major areas of interest are currently being pursued.
The first involves the development and application of structural methods to gain a more complete picture of how G proteins become activated and transmit signals within the context of the cell membrane. The second involves the use of small molecule chemistry to identify novel pathways necessary to satisfy the bioenergetics and metabolic requirement of cancer cells to proliferate at high rates and become invasive, with the ultimate goal of defining new strategies for therapeutic intervention. The third focuses on the recent identification of a new class of membrane vesicles that are shed by cancer cells and stem cells, with the goal being to understand how these vesicles play critical roles in the development of the malignant state and in stem cell biology.
Katt, W.P., and Cerione, R.A. (2013) Glutaminase regulation in cancer cells: a druggable chain of events. Drug Discov. Today S1359-6446, 00334-00336.
Lukey, M.J., Wilson, K.F., and Cerione, R.A. (2013) Therapeutic strategies impacting cancer cell glutamine metabolism. Future Med. Chem. 5, 1685-1700. PMC Journal – In Process.
Zhang, J., Antonyak, M.A., Singh, G., and Cerione, R.A. (2013) A mechanism for the upregulation of EGF receptor levels in glioblastomas. Cell Rep. 3, 2008-2020. PMCID: PMC3742030
Wilson, K.F., Erickson, J.W., Antonyak, M.A., and Cerione, R.A. (2013) Rho GTPases and their roles in cancer metabolism. Trends Mol. Med. 19, 74-82. PMCID: PMC3607349
Katt, W.P., Ramachandran, S., Erickson, J.W., and Cerione, R.A. (2012) Dibenzophenanthridines as inhibitors of glutaminase C and cancer cell proliferation. Mol. Cancer Ther. 11, 1269-1278. PMCID: PMC3620022
Johnson, J., Erickson, J.W., and Cerione, R.A. (2012) C-terminal di-arginine motif of Cdc42 protein is essential for binding to phosphatidylinositol 4,5 bisphosphate-containing membranes and inducing cellular transformation. J. Biol. Chem. 287, 5764-5774. PMCID: PMC3325590
Li, B., Antonyak, M.A., Zhang, J., and Cerione, R.A. (2012) RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells. Oncogene 31, 4740-4749. PMCID: PMC3607381
Antonyak, M.A., Li, B., Boroughs, L.K., Johnson, J.L., Druso, J.E., Bryant, K.L., Holowka, D.A., and Cerione, R.A. (2011) Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells. Proc. Natl. Acad. Sci. USA 108, 4852-4857. PMCID: PMC3064359 Highlight Article
Erickson, J.W., and Cerione, R.A. (2010) Glutaminase: A hot spot for regulation of cancer cell metabolism? Oncotarget 1, 734-740. PMCID: PMC3018840
Wang, J.B., Erickson, J.W., Fuji, R., Ramachandran, S., Gao, P., Dinavahi, R., Wilson, K.F., Ambrosio, A.L.B., Dias, S.M.G., Dang, C.V., and Cerione, R.A. (2010) Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 18, 207-219. PMCID: PMC3078749 Cover Article
Dias, S.M.G., Wilson, K.F., Rojas, K.S., Ambrosio, A.L.B., and Cerione, R.A. (2009) The molecular basis for the regulation of the cap-binding complex by the importins. Nat. Struct. Mol. Biol. 16, 930-937. PMCID: PMC2782468
Endo, M., Antonyak, M.A., and Cerione, R.A. (2009) Cdc42-mTOR signaling pathway controls Hes5 and Pax6 expression in retinoic acid-dependent neural differentiation. J. Biol. Chem. 284, 5107-5118. PMID: 19097998 Cover Article