Cancer therapy is often initially successful only to be followed by recurrence of drug resistant disease. I am interested in studying this phenomenon. Work in my lab has revealed an important signaling pathway involved in tumorigenesis: natriuretic peptide receptor A (NPRA). The loss of NPRA signaling reduces angiogenesis and tumor growth and NPRA modulates the homing of somatic stem cells to tumors by altering the expression of C-X-C chemokine receptor 4. We have also developed a 3D fibrous scaffold to use as a cell culture environment. I would like to apply these findings to the study of cancer stem cells. CSCs are a sub population of cancer cells that express stem cell transcription factors associated with-self renewal, are drug resistant and initiate metastasis. My hypothesis is that NPRA signaling modulates CXCR4 expression in cancer cells leading to metastasis and an increase in the CSC population. I will also investigate the effects of 3D culture on the CSC population.
Girard YK, Wang C, Ravi S, Howell MC, Mallela J, Alibrahim M, Green R, Hellermann G, Mohapatra SS, Mohapatra S. A 3D fibrous scaffold inducing tumoroids: a platform for anticancer drug development.PloS one. 8(10) : e75345, 2013.
MARK HOWELL, RYAN GREEN, ALEXIS KILLEEN, LAMAR WEDDERBURN, VINCENT PICASCIO, ALEJANDRO RABIONET,ZHENLING PENG, MAYA LARINA, BIN XUE, LUKASZ KURGAN, VL. NOT THAT RIGID MIDGETS AND NOT SO FLEXIBLE GIANTS: ON THE ABUNDANCE AND ROLES OF INTRINSIC DISORDER IN SHORT AND LONG PROTEINSJournal of Biological Systems. 20(4) : 471-511, 2012.
Kovacs G, Breydo L, Green R, Kis V, Puska G, Lőrincz P, Perju-Dumbrava L, Giera R, Pirker W, Lutz M, Lachmann I, Budka H, Uversky VN, Molnár K, László L. Intracellular processing of disease-associated α-synuclein in the human brain suggests prion-like cell-to-cell spreadNeurobiology of Disease. 69: 76-92, 2014.
