Genome Research Institute
Department of Molecular Oncogenesis
2180 E. Galbraith Rd.
Cincinnati, OH 45237-0505

Email Maria

Funding
Publications

Maria received her MD and PhD in physiology at Warsaw Medical School in Warsaw, Poland. She did postdoctoral research in the Department of Physiology at University of North Carolina in Chapel Hill in the laboratory of Dr. David Millhorn. She came to University of Cincinnati in 1994 as an assistant professor of Molecular and Cellular Physiology, and is currently a full professor at the Genome Research Institute. Her research interests are focused on the regulation of gene expression by hypoxia. Recently, her laboratory has worked on identifying novel substrates for the von Hippel-Lindau (pVHL) tumor suppressor protein complex. Biochemically, pVHL serves as a substrate-recognition molecule of the E3 ubiquitin ligase complex, whose most widely recognized activity is ubiquitylation of the alpha subunits of the hypoxia-inducible transcription factors, targeting them for degradation. pVHL is lost in 40 to 80% of malignant renal clear cell carcinoma cases, and in genetic VHL disease. Work in the C-K lab has led to the discovery that the large subunit of RNA Polymerase II, Rpb1, undergoes hydroxylation and ubiquitylation in a pVHL-dependent manner. Ongoing work in the lab is continuing to investigate the role of those biochemical modifications in the pathogenesis of kidney cancer.




Funding Support
Active grant support

2001-2006: RO1 NIH, HLB HL 58687
Title: “Regulation of gene expression by oxygen”
PI: M.F. Czyzyk-Krzeska

2004-2008: RO1, NIH, HLB HL 66312
Title: “Regulation of cell function by intermittent hypoxia”
PI: M.F. Czyzyk-Krzeska

2007-2010: DoD PR064135
Title: “Identification of Genes in Kidney Cancer Oncogenesis”
PI: M.F. Czyzyk-Krzeska



Publications

1:	Hui AS, Bauer AL, Striet JB, Schnell PO, Czyzyk-Krzeska MF Calcium signaling stimulates translation of HIF-alpha during hypoxia. FASEB J. 2006 Mar;20(3):466-75. PMID: 16507764 [PubMed - indexed for MEDLINE]

2:

Zakrzewska A, Schnell PO, Striet JB, Hui A, Robbins JR, Petrovic M, Conforti L, Gozal D, Wathelet MG, Czyzyk-Krzeska MF Hypoxia-activated metabolic pathway stimulates phosphorylation of p300 and CBP in oxygen-sensitive cells. J Neurochem. 2005 Sep;94(5):1288-96. PMID: 16000154 [PubMed - indexed for MEDLINE]

3:	Czyzyk-Krzeska MF, Meller J von Hippel-Lindau tumor suppressor: not only HIF's executioner. Trends Mol Med. 2004 Apr;10(4):146-9. PMID: 15162797 [PubMed - indexed for MEDLINE]

4:

Schnell PO, Ignacak ML, Bauer AL, Striet JB, Paulding WR, Czyzyk-Krzeska MF Regulation of tyrosine hydroxylase promoter activity by the von Hippel-Lindau tumor suppressor protein and hypoxia-inducible transcription factors. J Neurochem. 2003 Apr;85(2):483-91. PMID: 12675925 [PubMed - indexed for MEDLINE]

5:

Kuznetsova AV, Meller J, Schnell PO, Nash JA, Ignacak ML, Sanchez Y, Conaway JW, Conaway RC, Czyzyk-Krzeska MF von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination. Proc Natl Acad Sci U S A. 2003 Mar;100(5):2706-11. PMID: 12604794 [PubMed - indexed for MEDLINE]

6:	Kamura T, Sato S, Iwai K, Czyzyk-Krzeska M, Conaway RC, Conaway JW Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc Natl Acad Sci U S A. 2000 Sep;97(19):10430-5. PMID: 10973499 [PubMed - indexed for MEDLINE]