Department of Biochemistry and Molecular Biology
University of California, Davis, PhD, 1992
Howard Hughes Medical Institute, University of California, Postdoctoral fellow, 1993-1998
Cleveland State University, Assistant Professor, Department of Biological, Geological and Environmental Sciences, 1998 - 2004
Cleveland State University, Associate Professor, Department of Biological, Geological and Environmental Sciences, 2004 - 2006
University of Kansas Medical Center, Associate Professor, Department of Biochemistry and Molecular Biology, 2007 - present
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University of Kansas Medical Center
The focus of my lab is on mechanisms that regulate gene transcription during the development and function of the immune system. Currently, the major effort in my lab is to characterize the role of a family of transcription factors know as zinc finger X-linked duplicated (ZXD) in immune system function. Our earlier work demonstrated a role for two ZXD family members, ZXDA and ZXDC, in the transcription of major histocompatibility complex class II (MHC II) genes. More recently, we have established that ZXDC participates in regulating genes important for the development and activity of myeloid cells, particular those of the monocyte lineage. Our current model for the activity of ZXDC invokes two different mechanisms. First, ZXDC binds to and inhibits the activity of a transcriptional repressor B-cell lymphoma 6 protein (Bcl6), leading to increased transcription of specific genes, including the Chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemoattractant protein -1, MCP1). Secondly, one isoform of ZXDC interacts with chromatin modifying enzyme complexes, leading to changes in enhancer activity that regulates genes necessary for monocyte differentiation and function. We are currently pursuing the mechanistic differences and gene targets of the two ZXDC isoforms and further refining the models by which they alter transcription.
Another aspect of my laboratory's work is a robust collaboration with Dr. Andrei Belousov in the Department of Molecular and Integrative Physiology at KUMC, focused on the regulation and activity of the gap-junction protein connexin-36 (Cx36) in neuronal development and death following injury.
Knockdown of ZXDC by lentiviral transduction of human U937 cells leads to impairment of differentiation and associated gene expression.
Ramsey JE, Fontes JD. The Zinc Finger Transcription Factor ZXDC Activates CCL2 Gene Expression by Opposing BCL6-mediated Repression. Molec. Immunol., In press, 2013.
Belousov AB, Fontes JD. Neuronal gap junctions: making and breaking connections during development and injury. Trends Neurosci. 2013 Apr;36(4):227-36.
Belousov AB, Wang Y, Song JH, Denisova JV, Berman NE, Fontes JD. Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact. Neurosci Lett. 2012 Aug 22;524(1):16-9.
Park WM, Wang Y, Park S, Denisova JV, Fontes JD, Belousov AB. Interplay of chemical neurotransmitters regulates developmental increase in electrical synapses. J Neurosci. 2011 Apr 20;31(16):5909-20.
Aleksandrova A, Galkin O, Koneni R, Fontes JD. An N- and C-terminal truncated isoform of zinc finger X-linked duplicated C protein represses MHC class II transcription. Mol Cell Biochem. 2010 Apr;337(1-2):1-7.
Jambunathan S, Fontes JD. Sumoylation of the zinc finger protein ZXDC enhances the function of its transcriptional activation domain. Biol Chem. 2007 Sep;388(9):965-72.
Al-Kandari W, Koneni R, Navalgund V, Aleksandrova A, Jambunathan S, Fontes JD. The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription. J Mol Biol. 2007 Jun 22;369(5):1175-87.
Al-Kandari W, Jambunathan S, Navalgund V, Koneni R, Freer M, Parimi N, Mudhasani R, Fontes JD. ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription. Mol Immunol. 2007 Jan;44(4):311-21.
Joseph D. Fontes, Ph.D.