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.
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.
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.