Maria F. Czyzyk-Krzeska , MD,PhD

Sufficient access to nutrients is a fundamental requirement of cancer cells for survival and proliferation. Thus, tumor angiogenesis, which provides nutrients from the blood, is considered to be a hallmark of cancer and is a useful target for anti-cancer therapies. It is, however, increasingly clear that, in addition to extracellular sources of nutrients, cancer cells also efficiently utilize intracellular nutrients through the process of macroautophagy to drive oncogenic growth and survival.

Autophagic recycling of organelles, protein aggregates, and/or cytoplasm yields simple metabolites for use in cell growth or bioenergetics, and can destroy damaged structures to prevent toxicity. However, autophagy can be a double-edged sword: on the one hand, cancer cells exploit autophagy to enhance the nutrient supply, while on the other hand, too much autophagy leads to self-depletion and triggers cell death. At the same time, there is genetic evidence from mouse model systems that knockdown of certain canonical autophagic regulators, such as BECN1, ATG5, or ATG7, promotes tumor development. Opposing roles for autophagy in cancer—tumor-promoting versus tumor-suppressing—may result from differing interactions with cooperating oncogenes. Alternatively, the impact of autophagy in oncogenesis may be determined by differences in the formation of autophagic vacuoles carrying distinct cargos in a tissue- or starvation-specific manner.

There are multiple steps in autophagic pathways in which the specificity of the autophagic process is determined. Autophagy begins with the formation of a phagophore that can originate by de novo formation or from diverse sources, such as the plasma membrane, Golgi, endoplasmic reticulum, or outer mitochondrial membrane. A ubiquitin-like conjugation system generates an ATG12–ATG5 conjugate that, with ATG16L1, carries out a final E3-like conjugation of phosphatidylethanolamine (PE) to a family of proteins known as the LC3/GABARAP paralogs. The lipidated forms are then inserted into the autophagosome membrane where they recruit cargo by binding to adaptor proteins, such as SQSTM1/p62, NBR1, and CALCOCO2/NDP52, that seem to carry some level of specificity to certain cargos. Human cells have at least seven different LC3 paralogs (LC3A/B/B2/C and GABARAP/L1/L2), which indicates a biochemical richness that could lead to both specificity and redundancy.

Our recently published results show that differential engagement of LC3 paralogs identifies separate autophagic programs that exert either pro- or anti-tumorigenic activities in renal cell carcinoma. Both autophagic programs are regulated by the von Hippel-Lindau tumor suppressor protein (VHL) lost in renal cancer. VHL inhibits LC3B-mediated autophagy through induction of MIR204, which directly targets LC3B. In parallel, VHL, by inhibiting HIF, induces expression of LC3C, which carries tumor-suppressing autophagic activity (Fig. 1). The LC3B autophagic program supports tumor formation by VHL- renal cancer cells in orthotopic xenografts. LC3B expression is significantly increased in high-grade human ccRCC tumors as compared with lower grade tumors. The second program, mediated by a lesser-known LC3 paralog, LC3C, has tumor-suppressing activity. Knockdown of LC3C in VHL-expressing cells induces the formation of tumors that would otherwise be suppressed by VHL tumor suppressor function. In addition, LC3C expression is significantly higher in normal human kidney tissue as compared with ccRCC tumors.
Integrating our data with the established role of VHL in regulating angiogenesis produces a more global picture of VHL as a master tumor suppressor that regulates nutrient access for renal cancer cells from both extracellular and intracellular sources. 

Publications

Medical Degree: Warsaw Medical School

For the last 15 years, my laboratory has conducted mechanistic studies of signaling pathways and regulatory molecular mechanisms that regulate cancer cell survival and tumor growth in renal cancer.  In particular, we have focused our interests on the von Hippel-Lindau tumor suppressor (VHL), lost in majority of renal cancers, and autophagy. Renal cancer accounts for 2-3% of adult malignancies in the USA with clear cell renal carcinoma (ccRCC) as the main histological type. Current treatments include anti-angiogenic agents based on the understanding that the loss of VHL results in activation of HIF and VEGF. However, these treatments have a limited impact on survival. Thus, it is critical to identify novel pathways as specific targets for the development of new therapies. Autophagy is a tightly regulated homeostatic process which allows cells to eliminate defective structures and to recycle nutrients. In several cancers, including ccRCC, basic autophagy is elevated and necessary for tumor growth. Autophagy is also induced by inhibitors of angiogenesis, mTOR pathway or proteasome, leading to resistance to treatments. We established that in ccRCC, a specific LC3B-mediated autophagic program is activated by the loss of VHL, and LC3B activity contributes to tumor growth. Another autophagic program, mediated by LC3B paralog, LC3C, is stimulated by VHL and has tumor suppressing activity. Most recently we identified that two products of TRPM3 gene, microRNA 204 (miR-204) and transient receptor potential channel, TRPM3, have opposite roles in ccRCC. Mir-204 is induced by VHL and acts as a tumor suppressor inhibiting oncogenic autophagy, while TRPM3 acts as an oncogene and promotes oncogenic autophagy.
 


Publications

 

1991 -1994 Research assistant professor of Pediatrics, University of North Carolina , Chapel Hill, NC

1994 -1999 Assistant professor of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH

1999 -2005 Associate professor (with tenure), Molecular Cellular Physiology, University of Cincinnati, Cincinnati, OH

2003 -2005 Associate professor (with tenure), Genome Science, GRI, University of Cincinnati, Cincinnati, OH

2005 -2008 Professor, (with tenure), Department of Genome Science, and Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH

2008 -To Present Professor, (with tenure), Department of Cancer and Cell Biology, and Department of Molecular and Cellular Physiology , University of Cincinnati, Cincinnati, OH

2008 -To Present Co-Director, Cancer and Cell Biology Graduate Program, University of Cincinnati, Cincinnati, OH

Grant: #VA Billing Agreement Investigators:Bischoff, Megan; Czyzyk-Krzeska, Maria 07-01-2020 -06-30-2021 Department of Veterans Affairs VA Billing Agreement Megan Bischoff Role:PI $32,974.00 Awarded Level:Federal

Grant: #R01GM128216 Investigators:Czyzyk-Krzeska, Maria; Greis, Kenneth; Guan, Jun-lin; Meller, Jaroslaw 09-12-2019 -08-31-2023 National Institute of General Medical Sciences Mechanisms of selective autophagy Role:PI $314,708.00 Awarded Level:Federal

Grant: #VA Billing Agreement - Reigle Investigators:Czyzyk-Krzeska, Maria; Reigle, James 09-01-2017 -06-30-2021 Department of Veterans Affairs Tumor suppressing pathways in kidney cancer Role:PI $61,408.06 Active Level:Federal

Grant: #W81XWH-14-1-0347 / CA130028 Investigators:Czyzyk-Krzeska, Maria; Medvedovic, Mario; Meller, Jaroslaw 09-30-2014 -09-29-2016 Department of the Army Medical Research Acquisition Activity CA130028-Effects of Tobacco Smoke (TS) on growth of clear cell renal cell carcinoma (ccRCC) Role:PI $474,562.00 Awarded Level:Federal

Grant: #ECA Pandey Investigators:Czyzyk-Krzeska, Maria; Pandey, Raghav 07-01-2013 -06-30-2014 Department of Veterans Affairs VA ECA Pandey Role:Collaborator $27,820.00 Awarded Level:Federal

Grant: #R01 CA122346 Investigators:Czyzyk-Krzeska, Maria; Meller, Jaroslaw 04-01-2013 -03-31-2018 National Cancer Institute Molecular Mechanisms in Renal Cancer Role:PI $291,425.00 Active Level:Federal

Grant: #R01CA168815 Investigators:Czyzyk-Krzeska, Maria; Plas, David 04-01-2013 -03-31-2018 National Cancer Institute Metabolic Adaptive Responses in Cancer Role:Collaborator $427,706.00 Active Level:Federal

Grant: #BHDF Cincinnati Research Agreement Investigators:Czyzyk-Krzeska, Maria 03-01-2012 -02-28-2013 Myrovlytis Trust FLCN Tumor Suppressing Networks Role:PI $86,035.00 Active Level:Foreign Non-Profit

Grant: #BHDF Cincinnati Research Agreement 2 Investigators:Czyzyk-Krzeska, Maria 03-01-2012 -02-28-2013 Myrovlytis Trust Nephronectin as a Target Gene for FLCN Role:PI $50,000.00 Active Level:Foreign Non-Profit

Grant: #B101BX0011100-02 Investigators:Maria F Czyzyk-Krzeska 07-01-2011 -06-30-2015 Veteran Administration Research Service Tumor suppressing pathwyas in renal cancer

Grant: #SRS 007633 Investigators:Czyzyk-Krzeska, Maria; Hall, Daniel 07-01-2011 -06-30-2013 Department of Veterans Affairs Intergovernmental Personnel Act Agreement for Danny Hall Role:PI $41,025.00 Active Level:Federal

Grant: #SRS 007642 Investigators:Czyzyk-Krzeska, Maria; Greis, Kenneth 07-01-2011 -06-30-2015 Department of Veterans Affairs Intergovernmental Personnel Act Agreement for Ken Greis Role:PI $45,372.00 Active Level:Federal

Grant: #SRS 007643 Investigators:Czyzyk-Krzeska, Maria; Kellner, Emily 07-01-2011 -04-30-2015 Department of Veterans Affairs Intergovernmental Personnel Act Agreement for Emily Kellner Role:PI $216,013.00 Active Level:Federal

Grant: #SRS 007647 Investigators:Czyzyk-Krzeska, Maria; Meller, Jaroslaw 07-01-2011 -04-30-2015 Department of Veterans Affairs Intergovernmental Personnel Act Agreement for Jaroslow Meller Role:PI $34,172.00 Active Level:Federal

Grant: #SRS 006482 Investigators:Czyzyk-Krzeska, Maria 09-01-2009 -03-31-2012 Myrovlytis Trust Tumor Suppressor Networks: Regulation of FLCN Expression by VHL in Renal Cancer Role:PI $142,800.00 Active Level:Foreign Non-Profit

Grant: #R01 CA122346 Investigators:Czyzyk-Krzeska, Maria 09-01-2007 -03-31-2013 National Cancer Institute Role of Ubiquitylation in Renal Cancer Role:PI $1,551,608.00 Active Level:Federal

Grant: #R01 CA 122341, NIH/NCI Investigators:Maria F Czyzyk-Krzeska 09-01-2007 -03-01-2018 Molecular Mechanisms of Renal Cancer Role:PI Active

Grant: #W81XWH-07-2-0026 Investigators:Czyzyk-Krzeska, Maria 02-01-2007 -07-31-2010 Department of the Army Medical Research Acquisition Activity Identification of Genes in Kidney Cancer Oncogenesis Role:PI $932,919.00 Active Level:Federal

Grant: #000086 Investigators:Czyzyk-Krzeska, Maria 07-01-2006 -06-30-2007 Department of Energy ORISE AFRL/HEP Fellowship Role:PI $31,763.64 Closed Level:Federal

Grant: #HL 066312 Investigators:Czyzyk-Krzeska, Maria 09-01-2004 -05-31-2008 National Heart, Lung and Blood Institute Regulation of Cell Function by Intermittent Hypoxia Role:PI $1,204,877.00 Closed Level:Federal

Grant: #5-R01-HL-58687-09-A0-S0-E0 Investigators:Czyzyk-Krzeska, Maria 04-01-2001 -03-31-2007 National Heart, Lung and Blood Institute Regulation of Gene Expression by Oxygen Role:PI $1,708,000.00 Closed Level:Federal

Grant: #RGS-01-047-01-GMC-04-A0-S0-E0 Investigators:Czyzyk-Krzeska, Maria 01-01-2001 -12-31-2004 American Cancer Society - National Chapter Regulation of Gene Expression by Von Hippel-Lindau Tumor Suppressor Complex Role:PI $948,000.00 Closed Level:Private Non-Profit

Grant: #5-R01-HL-66312-04-A0-S0-E0 Investigators:Czyzyk-Krzeska, Maria 09-30-2000 -08-31-2004 National Heart, Lung and Blood Institute Regulation of Gene Expression During Intermittent Hypoxia Role:PI $1,071,000.00 Closed Level:Federal

Grant: #VHL-01-02-A0-S0-E0 Investigators:Czyzyk-Krzeska, Maria 07-01-1999 -06-30-2001 Von Hippel-Lindau Family Alliance Von Hippel-Lindau Function in Pheochromocytoma Role:PI $70,000.00 Closed Level:Private Non-Profit

Grant: #9750110N-03-A0-S0-E0 Investigators:Czyzyk-Krzeska, Maria 01-01-1998 -12-31-2000 American Heart Association - National Chapter Post-Transcriptional Regulation of Erythropoietin Gene Expression by Hypoxia Role:PI $165,000.00 Closed Level:Private Non-Profit

Grant: #P&G-25-01-A0-S1-E1 Investigators:Czyzyk-Krzeska, Maria 06-30-1997 -12-31-1999 Procter & Gamble Company Identification of the Functional Sites within the 3' Untranslated Region of VEGF mRNA Role:PI $123,200.00 Closed Level:Industry

Grant: #5-R01-HL-58687-04-A0-S0-E0 Investigators:Czyzyk-Krzeska, Maria 04-01-1997 -03-31-2001 National Heart, Lung and Blood Institute Posttranscriptional Regulation Catecholamine Synthesis Role:PI $1,137,545.00 Closed Level:Federal

Grant: #5-R29-HL-51078-05-A0-S0-E0 Investigators:Czyzyk-Krzeska, Maria 07-01-1994 -11-30-1999 National Heart, Lung and Blood Institute Regulation of Gene Expression by Oxygen Role:PI $394,448.00 Closed Level:Federal

Grant: #VA Billing Agreement Investigators:Czyzyk-Krzeska, Maria; Secic, Dina 07-01-2021 -06-30-2022 Department of Veterans Affairs VA Billing Agreement Dina Secic Role:PI 32868.00 Hold Level:Federal

Grant: #VA billing Investigators:Czyzyk-Krzeska, Maria; Yang, Juechen 10-01-2021 -09-30-2022 Department of Veterans Affairs Tumor Suppressing Pathways in Kidney Cancer Role:PI 20756.00 Hold Level:Federal

Grant: #VA Billing agreement for Martines ( 04-30-2023 -08-19-2023 Department of Veterans Affairs VA Billing Agreement Martines (Mary CK) Role:PI 7175.04 Hold Level:Federal

Grant: #VA Billing agreement for Martines ( 04-30-2023 -08-19-2023 Department of Veterans Affairs VA Billing Agreement Martines (Mary CK) Role:PI 7175.04 Hold Level:Federal

Grant: #VA BA for Venkat (ONCA-002-15F) 06-01-2023 -06-30-2024 Department of Veterans Affairs Tumor Suppressing Pathways in Kidney Cancer Role:PI 14332.03 Hold Level:Federal

Grant: #VA BA for Venkat (ONCA-002-15F) 06-01-2023 -06-30-2024 Department of Veterans Affairs Tumor Suppressing Pathways in Kidney Cancer Role:PI 14332.03 Hold Level:Federal

Investigators:Czyzyk-Krzeska, Maria 07-01-2023 -06-30-2024 Department of Veterans Affairs VA Billing Agreement Stenke (Maria CK) Role:PI 12698.40 Hold Level:Federal

Grant: #R01CA287260 Investigators:Cunningham, John; Czyzyk-Krzeska, Maria; Meller, Jaroslaw; Vest, Katherine 09-20-2023 -08-31-2028 National Cancer Institute Metabolic effects of cooper in renal cancer Role:PI 693769.38 Hold Level:Federal

Grant: #ACS: IRG-23-1141524-01-IRG Investigators:Czyzyk-Krzeska, Maria; Plas, David 01-01-2024 -12-31-2026 American Cancer Society - National Chapter Institutional Research Grant Role:Collaborator 360000.00 Hold Level:Non Profit

Grant: #Va BA for Szczepkowski , 2024-25 08-01-2024 -07-31-2025 Department of Veterans Affairs VA Billing Agreement Szczepkowski (Maria CK) Role:PI 16623.36 Hold Level:Federal

Grant: #Va BA for Szczepkowski , 2024-25 08-01-2024 -07-31-2025 Department of Veterans Affairs VA Billing Agreement Szczepkowski (Maria CK) Role:PI 16623.36 Hold Level:Federal

Peer Reviewed Publications

Czyzyk-Krzeska, Maria F; Landero Figueroa, Julio A; Gulati, Shuchi; Cunningham, John T; Meller, Jarek; ShamsaeI, Behrouz; Vemuri, Bhargav; Plas, David R (2021. ) Molecular and Metabolic Subtypes in Sporadic and Inherited Clear Cell Renal Cell Carcinoma.Genes, , 12 (3 ) , More Information

Czyzyk-Krzeska, Maria F; Meller, Jarek; Landero Figueroa, Julio A; Plas, David R; Cunningham, John T (2021. ) Metabolic subtypes of clear cell renal cell carcinoma defined by tobacco smoking.Molecular & cellular oncology, , 8 (2 ) ,1859917 More Information

Reigle, James; Secic, Dina; Biesiada, Jacek; Wetzel, Collin; Shamsaei, Behrouz; Chu, Johnson; Zang, Yuanwei; Zhang, Xiang; Talbot, Nicholas J; Bischoff, Megan E; Zhang, Yongzhen; Thakar, Charuhas V; Gaitonde, Krishnanath; Sidana, Abhinav; Bui, Hai; Cunningham, John T; Zhang, Qing; Schmidt, Laura S; Linehan, W Marston; Medvedovic, Mario; Plas, David R; Figueroa, Julio A Landero; Meller, Jarek; Czyzyk-Krzeska, Maria F (2021. ) Tobacco smoking induces metabolic reprogramming of renal cell carcinoma.The Journal of clinical investigation, , 131 (1 ) , More Information

Bischoff, Megan E; Zang, Yuanwei; Chu, Johnson; Price, Adam D; Ehmer, Birgit; Talbot, Nicholas J; Newbold, Michael J; Paul, Anurag; Guan, Jun-Lin; Plas, David R; Meller, Jarek; Czyzyk-Krzeska, Maria F (2021. ) Selective MAP1LC3C (LC3C) autophagy requires noncanonical regulators and the C-terminal peptide.The Journal of cell biology, , 220 (7 ) , More Information

Zhang, Yuqian; Rana, Ankit; Stratton, Yiwen; Czyzyk-Krzeska, Maria F; Esfandiari, Leyla (2017. ) Sequence-Specific Detection of MicroRNAs Related to Clear Cell Renal Cell Carcinoma at fM Concentration by an Electroosmotically Driven Nanopore-Based Device.Analytical chemistry, , 89 (17 ) ,9201-9208 More Information

Klionsky DJ, Czyzyk-Krzeska MF, et al. (2016. ) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy, , 12 ,1-222 More Information

N.G. Cost, M.F. Czyzyk-Krzeska (2015. ) Regulation of autophagy by two products of one gene: TRPM3 and miR-204 Molecular and Cellular Oncology.Molecular and Cellular Oncology, , 2 (4 ) , More Information

Cost, Nicolas G; Czyzyk-Krzeska, Maria F (2015. ) Regulation of autophagy by two products of one gene: TRPM3 and miR-204.Molecular & cellular oncology, , 2 (4 ) ,e1002712 More Information

Hall, Daniel P; Cost, Nicholas G; Hegde, Shailaja; Kellner, Emily; Mikhaylova, Olga; Stratton, Yiwen; Ehmer, Birgit; Abplanalp, William A; Pandey, Raghav; Biesiada, Jacek; Harteneck, Christian; Plas, David R; Meller, Jarek; Czyzyk-Krzeska, Maria F (2014. ) TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma.Cancer cell, , 26 (5 ) ,738-53 More Information

Czyzyk-Krzeska, M F; Zhang, X (2014. ) MiR-155 at the heart of oncogenic pathways.Oncogene, , 33 (6 ) ,677-8 More Information

Czyzyk-Krzeska, Maria F; McCormack, Francis X (2013. ) Birt-Hogg-Dubé syndrome.Familial cancer, , 12 (3 ) ,355-6 More Information

Bastola, Prabhat; Stratton, Yiwen; Kellner, Emily; Mikhaylova, Olga; Yi, Ying; Sartor, Maureen A; Medvedovic, Mario; Biesiada, Jacek; Meller, Jarek; Czyzyk-Krzeska, Maria F (2013. ) Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy.PloS one, , 8 (7 ) ,e70030 More Information

Kawedia, Jitesh D; Yang, Fan; Sartor, Maureen A; Gozal, David; Czyzyk-Krzeska, Maria; Menon, Anil G (2013. ) Hypoxia and hypoxia mimetics decrease aquaporin 5 (AQP5) expression through both hypoxia inducible factor-1alpha and proteasome-mediated pathways.PloS one, , 8 (3 ) ,e57541 More Information

Mikhaylova, Olga; Stratton, Yiwen; Hall, Daniel; Kellner, Emily; Ehmer, Birgit; Drew, Angela F; Gallo, Catherine A; Plas, DR; Biesiada, Jacek; Meller, Jarek; Czyzyk-Krzeska, Maria F (2012. ) VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma.Cancer cell, , 21 (4 ) ,532-46 More Information

Czyzyk-Krzeska, Maria F; Meller, Jarek; Plas, David R (2012. ) Not all autophagy is equal.Autophagy, , 8 (7 ) ,1155-6 More Information

Yi, Ying; Mikhaylova, Olga; Mamedova, Aygun; Bastola, Prabhat; Biesiada, Jacek; Alshaikh, Enas; Levin, Linda; Sheridan, Rachel M; Meller, Jarek; Czyzyk-Krzeska, Maria F (2010. ) von Hippel-Lindau-dependent patterns of RNA polymerase II hydroxylation in human renal clear cell carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research, , 16 (21 ) ,5142-52 More Information

Siroky, Brian J; Czyzyk-Krzeska, Maria F; Bissler, John J (2009. ) Renal involvement in tuberous sclerosis complex and von Hippel-Lindau disease: shared disease mechanisms?.Nature clinical practice. Nephrology, , 5 (3 ) ,143-56 More Information

Ignacak, M L; Harbaugh, S V; Dayyat, E; Row, B W; Gozal, D; Czyzyk-Krzeska, M F (2009. ) Intermittent hypoxia regulates RNA polymerase II in hippocampus and prefrontal cortex.Neuroscience, , 158 (4 ) ,1436-45 More Information

Haffey, Wendy D; Mikhaylova, Olga; Meller, Jarek; Yi, Ying; Greis, Kenneth D; Czyzyk-Krzeska, Maria F (2009. ) iTRAQ proteomic identification of pVHL-dependent and -independent targets of Egln1 prolyl hydroxylase knockdown in renal carcinoma cells.Advances in enzyme regulation, , 49 (1 ) ,121-32 More Information

Mikhaylova, Olga; Ignacak, Monika L; Barankiewicz, Teresa J; Harbaugh, Svetlana V; Yi, Ying; Maxwell, Patrick H; Schneider, Martin; Van Geyte, Katie; Carmeliet, Peter; Revelo, Monica P; Wyder, Michael; Greis, Kenneth D; Meller, Jarek; Czyzyk-Krzeska, Maria F (2008. ) The von Hippel-Lindau tumor suppressor protein and Egl-9-Type proline hydroxylases regulate the large subunit of RNA polymerase II in response to oxidative stress.Molecular and cellular biology, , 28 (8 ) ,2701-17 More Information

Hui, Anna S; Bauer, Amy L; Striet, Justin B; Schnell, Phillip O; Czyzyk-Krzeska, Maria F (2006. ) Calcium signaling stimulates translation of HIF-alpha during hypoxia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology, , 20 (3 ) ,466-75 More Information

Zakrzewska, Adriana; Schnell, Phillip O; Striet, Justin B; Hui, Anna; Robbins, Jennifer R; Petrovic, Milan; Conforti, Laura; Gozal, David; Wathelet, Marc G; Czyzyk-Krzeska, Maria F (2005. ) Hypoxia-activated metabolic pathway stimulates phosphorylation of p300 and CBP in oxygen-sensitive cells.Journal of neurochemistry, , 94 (5 ) ,1288-96 More Information

Gozal, Evelyne; Shah, Zahoor A; Pequignot, Jean-Marc; Pequignot, Jacqueline; Sachleben, Leroy R; Czyzyk-Krzeska, Maria F; Li, Richard C; Guo, Shang-Z; Gozal, David (2005. ) Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia.Journal of applied physiology (Bethesda, Md. : 1985), , 99 (2 ) ,642-9 More Information

Czyzyk-Krzeska, Maria F; Meller, Jaroslaw (2004. ) von Hippel-Lindau tumor suppressor: not only HIF's executioner. Trends in molecular medicine, , 10 (4 ) ,146-9

Hui, Anna S; Striet, Justin B; Gudelsky, Gary; Soukhova, Galia K; Gozal, Evelyne; Beitner-Johnson, Dana; Guo, Shang-Z; Sachleben, Leroy R; Haycock, John W; Gozal, David; Czyzyk-Krzeska, Maria F (2003. ) Regulation of catecholamines by sustained and intermittent hypoxia in neuroendocrine cells and sympathetic neurons.Hypertension, , 42 (6 ) ,1130-6 More Information

Schnell, Phillip O; Ignacak, Monika L; Bauer, Amy L; Striet, Justin B; Paulding, Waltke R; Czyzyk-Krzeska, Maria F (2003. ) Regulation of tyrosine hydroxylase promoter activity by the von Hippel-Lindau tumor suppressor protein and hypoxia-inducible transcription factors. Journal of neurochemistry, , 85 (2 ) ,483-91

Kuznetsova, Anna V; Meller, Jaroslaw; Schnell, Phillip O; Nash, James A; Ignacak, Monika L; Sanchez, Yolanda; Conaway, Joan W; Conaway, Ronald C; Czyzyk-Krzeska, Maria F (2003. ) von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination.Proceedings of the National Academy of Sciences of the United States of America, , 100 (5 ) ,2706-11 More Information

Paulding, Waltke R; Schnell, Phillip O; Bauer, Amy L; Striet, Justin B; Nash, James A; Kuznetsova, Anna V; Czyzyk-Krzeska, Maria F (2002. ) Regulation of gene expression for neurotransmitters during adaptation to hypoxia in oxygen-sensitive neuroendocrine cells.Microscopy research and technique, , 59 (3 ) ,178-87 More Information

Yeap, Bu B; Voon, Dominic C; Vivian, Julian P; McCulloch, Ross K; Thomson, Andrew M; Giles, Keith M; Czyzyk-Krzeska, Maria F; Furneaux, Henry; Wilce, Matthew C J; Wilce, Jackie A; Leedman, Peter J (2002. ) Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif within the 3'-untranslated region of the androgen receptor messenger RNA.The Journal of biological chemistry, , 277 (30 ) ,27183-92 More Information

Bauer, Amy L; Paulding, Waltke R; Striet, Justin B; Schnell, Phillip O; Czyzyk-Krzeska, Maria F (2002. ) Endogenous von Hippel-Lindau tumor suppressor protein regulates catecholaminergic phenotype in PC12 cells. Cancer research, , 62 (6 ) ,1682-7

Akeno, Nagako; Robins, Jared; Zhang, Mei; Czyzyk-Krzeska, Maria F; Clemens, Thomas L (2002. ) Induction of vascular endothelial growth factor by IGF-I in osteoblast-like cells is mediated by the PI3K signaling pathway through the hypoxia-inducible factor-2alpha.Endocrinology, , 143 (2 ) ,420-5 More Information

Akeno, N; Czyzyk-Krzeska, M F; Gross, T S; Clemens, T L (2001. ) Hypoxia induces vascular endothelial growth factor gene transcription in human osteoblast-like cells through the hypoxia-inducible factor-2alpha.Endocrinology, , 142 (2 ) ,959-62 More Information

Alterio, J; Mallet, J; Biguet, N F (2001. ) Multiple complexes involved in tyrosine hydroxylase mRNA stability in rat adrenal medulla, after reserpine stimulation.Molecular and cellular neurosciences, , 17 (1 ) ,179-89 More Information

Kamura, T; Sato, S; Iwai, K; Czyzyk-Krzeska, M; Conaway, R C; Conaway, J W (2000. ) Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex.Proceedings of the National Academy of Sciences of the United States of America, , 97 (19 ) ,10430-5 More Information

Paulding, W R; Czyzyk-Krzeska, M F (2000. ) Hypoxia-induced regulation of mRNA stability.Advances in experimental medicine and biology, , 475 ,111-21 More Information

Kroll, S L; Paulding, W R; Schnell, P O; Barton, M C; Conaway, J W; Conaway, R C; Czyzyk-Krzeska, M F (1999. ) von Hippel-Lindau protein induces hypoxia-regulated arrest of tyrosine hydroxylase transcript elongation in pheochromocytoma cells. The Journal of biological chemistry, , 274 (42 ) ,30109-14

Czyzyk-Krzeska, M F; Bendixen, A C (1999. ) Identification of the poly(C) binding protein in the complex associated with the 3' untranslated region of erythropoietin messenger RNA. Blood, , 93 (6 ) ,2111-20

Paulding, W R; Czyzyk-Krzeska, M F (1999. ) Regulation of tyrosine hydroxylase mRNA stability by protein-binding, pyrimidine-rich sequence in the 3'-untranslated region. The Journal of biological chemistry, , 274 (4 ) ,2532-8

Kroll, S L; Czyzyk-Krzeska, M F (1998. ) Role of H2O2 and heme-containing O2 sensors in hypoxic regulation of tyrosine hydroxylase gene expression. The American journal of physiology, , 274 (1 Pt 1 ) ,C167-74

Czyzyk-Krzeska, M F (1997. ) Molecular aspects of oxygen sensing in physiological adaptation to hypoxia. Respiration physiology, , 110 (2-3 ) ,99-111

Czyzyk-Krzeska, M F; Paulding, W R; Beresh, J E; Kroll, S L (1997. ) Post-transcriptional regulation of tyrosine hydroxylase gene expression by oxygen in PC12 cells. Kidney international, , 51 (2 ) ,585-90

Zhu, W H; Conforti, L; Czyzyk-Krzeska, M F; Millhorn, D E (1996. ) Membrane depolarization in PC-12 cells during hypoxia is regulated by an O2-sensitive K+ current. The American journal of physiology, , 271 (2 Pt 1 ) ,C658-65

Czyzyk-Krzeska, M F; Beresh, J E (1996. ) Characterization of the hypoxia-inducible protein binding site within the pyrimidine-rich tract in the 3'-untranslated region of the tyrosine hydroxylase mRNA. The Journal of biological chemistry, , 271 (6 ) ,3293-9

Czyzyk-Krzeska, M F; Paulding, W R; Lipski, J; Beresh, J E; Kroll, S L (1996. ) Regulation of tyrosine hydroxylase mRNA stability by oxygen in PC12 cells. Advances in experimental medicine and biology, , 410 ,143-50

Norris, M L; Millhorn, D E (1995. ) Hypoxia-induced protein binding to O2-responsive sequences on the tyrosine hydroxylase gene. The Journal of biological chemistry, , 270 (40 ) ,23774-9

Chen, J; Dinger, B; Fidone, S J (1995. ) Second messenger regulation of tyrosine hydroxylase gene expression in rat carotid body. Biological signals, , 4 (5 ) ,277-85

Czyzyk-Krzeska, M F; Dominski, Z; Kole, R; Millhorn, D E (1994. ) Hypoxia stimulates binding of a cytoplasmic protein to a pyrimidine-rich sequence in the 3'-untranslated region of rat tyrosine hydroxylase mRNA. The Journal of biological chemistry, , 269 (13 ) ,9940-5

Czyzyk-Krzeska, M F; Furnari, B A; Lawson, E E; Millhorn, D E (1994. ) Hypoxia increases rate of transcription and stability of tyrosine hydroxylase mRNA in pheochromocytoma (PC12) cells. The Journal of biological chemistry, , 269 (1 ) ,760-4

Millhorn, D E; Czyzyk-Krzeska, M; Bayliss, D A; Lawson, E E (1993. ) Regulation of gene expression by hypoxia. Sleep, , 16 (8 Suppl ) ,S44-8

Czyzyk-Krzeska, M F; Lawson, E E; Millhorn, D E (1992. ) Expression of D2 dopamine receptor mRNA in the arterial chemoreceptor afferent pathway. Journal of the autonomic nervous system, , 41 (1-2 ) ,31-9

Czyzyk-Krzeska, M F; Bayliss, D A; Lawson, E E; Millhorn, D E (1992. ) Regulation of tyrosine hydroxylase gene expression in the rat carotid body by hypoxia. Journal of neurochemistry, , 58 (4 ) ,1538-46

Czyzyk-Krzeska, M F; Bayliss, D A; Lawson, E E; Millhorn, D E (1991. ) Expression of messenger RNAs for peptides and tyrosine hydroxylase in primary sensory neurons that innervate arterial baroreceptors and chemoreceptors. Neuroscience letters, , 129 (1 ) ,98-102

Lawson, E E; Richter, D W; Czyzyk-Krzeska, M F; Bischoff, A; Rudesill, R C (1991. ) Respiratory neuronal activity during apnea and other breathing patterns induced by laryngeal stimulation. Journal of applied physiology (Bethesda, Md. : 1985), , 70 (6 ) ,2742-9

Czyzyk-Krzeska, M F; Lawson, E E (1991. ) Synaptic events in ventral respiratory neurones during apnoea induced by laryngeal nerve stimulation in neonatal pig. The Journal of physiology, , 436 ,131-47

Czyzyk-Krzeska, M F; Bayliss, D A; Seroogy, K B; Millhorn, D E (1991. ) Gene expression for peptides in neurons of the petrosal and nodose ganglia in rat. Experimental brain research, , 83 (2 ) ,411-8

Czyzyk-Krzeska, M F; Trzebski, A (1990. ) Respiratory-related discharge pattern of sympathetic nerve activity in the spontaneously hypertensive rat. The Journal of physiology, , 426 ,355-68

Czyzyk-Krzeska, M F; Trzebski, A (1990. ) Respiratory modulation of the cutaneous somatosympathetic reflex in normotensive (WKY) and in spontaneously hypertensive rats (SHR): species and strain-dependent patterns. Acta neurobiologiae experimentalis, , 50 (3 ) ,47-60

Krzeski, R; Trzebski, A; Czyzyk-Krzeska, M F (1990. ) Opposite excitatory and inhibitory effects of central administration of glucagon and of insulin upon the sympathetic cervical and adrenal nerve activities in the rat. Acta physiologica Polonica, , 41 (4-6 ) ,115-21

Krzeski, R; Czyzyk-Krzeska, M F; Trzebski, A; Millhorn, D E (1989. ) Centrally administered glucagon stimulates sympathetic nerve activity in rat. Brain research, , 504 (2 ) ,297-300

Millhorn, D E; Bayliss, D A; Erickson, J T; Gallman, E A; Szymeczek, C L; Czyzyk-Krzeska, M; Dean, J B (1989. ) Cellular and molecular mechanisms of chemical synaptic transmission. The American journal of physiology, , 257 (6 Pt 1 ) ,L289-310

Dean, J B; Czyzyk-Krzeska, M; Millhorn, D E (1989. ) Experimentally induced postinhibitory rebound in rat nucleus ambiguus is dependent on hyperpolarization parameters and membrane potential. Neuroscience research, , 6 (5 ) ,487-93

Verma, Rita; Aggarwal, Parul; Bischoff, Megan E; Reigle, James; Secic, Dina; Wetzel, Collin; VandenHeuvel, Katherine; Biesiada, Jacek; Ehmer, Birgit; Landero Figueroa, Julio A; Plas, David R; Medvedovic, Mario; Meller, Jarek; Czyzyk-Krzeska, Maria F (2023. ) Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells.The Journal of biological chemistry, , 299 (5 ) ,104663 More Information

Bischoff, Megan E; Shamsaei, Behrouz; Yang, Juechen; Secic, Dina; Vemuri, Bhargav; Reisz, Julie A; D'Alessandro, Angelo; Bartolacci, Caterina; Adamczak, Rafal; Schmidt, Lucas; Wang, Jiang; Martines, Amelia; Biesiada, Jacek; Vest, Katherine E; Scaglioni, Pier P; Plas, David R; Patra, Krushna C; Gulati, Shuchi; Figueroa, Julio A Landero; Meller, Jarek; Cunningham, J Tom; Czyzyk-Krzeska, Maria F (2024. ) Copper drives remodeling of metabolic state and progression of clear cell renal cell carcinoma.bioRxiv : the preprint server for biology, , More Information

Bischoff, Megan E; Shamsaei, Behrouz; Yang, Juechen; Secic, Dina; Vemuri, Bhargav; Reisz, Julie A; D'Alessandro, Angelo; Bartolacci, Caterina; Adamczak, Rafal; Schmidt, Lucas; Wang, Jiang; Martines, Amelia; Venkat, Jahnavi; Toffessi Tcheuyap, Vanina; Biesiada, Jacek; Behrmann, Catherine A; Vest, Katherine E; Brugarolas, James; Scaglioni, Pier Paolo; Plas, David R; Patra, Krushna C; Gulati, Shuchi; Landero Figueroa, Julio A; Meller, Jarek; Cunningham, John T; Czyzyk-Krzeska, Maria F (2024. ) Copper drives remodeling of metabolic state and progression of clear cell renal cell carcinoma.Cancer discovery, , More Information

Thorman, Alexander W; Reigle, James; Chutipongtanate, Somchai; Yang, Juechen; Shamsaei, Behrouz; Pilarczyk, Marcin; Fazel-Najafabadi, Mehdi; Adamczak, Rafal; Kouril, Michal; Bhatnagar, Surbhi; Hummel, Sarah; Niu, Wen; Morrow, Ardythe L; Czyzyk-Krzeska, Maria F; McCullumsmith, Robert; Seibel, William; Nassar, Nicolas; Zheng, Yi; Hildeman, David A; Medvedovic, Mario; Herr, Andrew B; Meller, Jarek (2024. ) Accelerating drug discovery and repurposing by combining transcriptional signature connectivity with docking.Science advances, , 10 (35 ) ,eadj3010 More Information

Behrmann, Catherine A; Ennis, Kelli N; Sarma, Pranjal; Wetzel, Collin; Clark, Nicholas A; Von Handorf, Kate M; Vallabhapurapu, Subrahmanya; Andreani, Cristina; Reigle, James; Scaglioni, Pier Paolo; Meller, Jarek; Czyzyk-Krzeska, Maria F; Kendler, Ady; Qi, Xiaoyang; Sarkaria, Jann N; Medvedovic, Mario; Sengupta, Soma; Dasgupta, Biplab; Plas, David R (2024. ) Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma.Cancer research communications, , 4 (8 ) ,2215-2227 More Information

1986 MD with Honors

1988 Ph.D. with Distinction

1989 Young Investigator Award - International Society for Arterial Chemoreception

1993 -1996 Parker B. Francis Fellowship

1996 -1998 NARSAD Young Investigator Award

Pc,Cell,Cobalt,Nickel,Hypoxia,Tyrosine,Hemoprotein,Carotid Body,Messenger Rna,Monooxygenase,Oxygen Tension,Phosphorylation,Neuropharmacology,Neurotrophic Factor,Oxidation Reduction,Rna Binding Protein,Protein Biosynthesis,Genetic Transcription,Nucleic Acid Sequence,Nucleic Acid Metabolism,Gel Mobility Shift Assay,Gene Induction Repression,Sympathetic Nervous System,Posttranscriptional Rna Processing

2000 -2005: Member of Editorial Board J. Biol. Chem.,

2006 -2011: Member Editorial Board, J. Biol. Chem.,

2006 -2011: Standing Member Tumor Biology Study Section, ACS (national),

2006: Member AACR,

2007 -To Present: Standing member Cancer Etiology Study Section, NIH, NCI ,

2007 -To Present: Research Advisory Board VHL Family Foundation,

2008 -To Present: Medical Advisory Board Kidney Cancer Association,

2008 -To Present: Medical Advisory Board Kidney Cancer: Action to Cure,

Academic - Vontz Center for Molecular Studies
3125 Eden Avenue
Cincinnati  Ohio, 45267
Phone: 513-558-1957
maria.czyzyk-krzeska@uc.edu