The VICC.ORG Directory of Doctors, Healthcare Providers & Researchers
Volker H. Haase, M.D.
See also:
Associate Professor
Researcher
Contact Information:
Vanderbilt University Medical Center
1161 21st Ave 37232 , S-3223 MCN
Nashville, TN 37232-2372
615-322-4794
Fax: 615-343-7156
Research Description
The Haase laboratory studies the VHL/HIF oxygen-sensing pathway and uses conditional gene targeting technology and transgenesis, as well as biochemical and functional genomics approaches to define the specific roles of the von Hippel-Lindau (VHL) tumor suppressor and individual HIF transcription factors in tumorigenesis, acute ischemia and chronic hypoxic injury, as well as erythropoiesis and iron metabolism. Hypoxia-Inducible Factors HIF-1 and HIF-2 are oxygen-sensitive basic helix-loop-helix transcription factors, which regulate biological processes that facilitate both oxygen delivery and cellular adaptation to oxygen deprivation. HIFs consist of an oxygen-sensitive alpha-subunit, HIF-alpha and a constitutively expressed beta-subunit, HIF-beta, and regulate the expression of genes that are involved in energy metabolism, angiogenesis, erythropoiesis and iron metabolism, cell proliferation, apoptosis and other biological processes. Under conditions of normal oxygen tension HIF-alpha is hydroxylated and targeted for rapid proteasomal degradation by the VHL/E3-ubiquitin ligase. When cells experience hypoxia, HIF-alpha is stabilized and either dimerizes with HIF-beta in the nucleus to form transcriptionally active HIF executing the canonical hypoxia response, or it physically interacts with other non-HIF proteins, enabling convergence of HIF oxygen sensing with other signaling pathways. Since HIF increases the expression of cytoprotective factors and erythropoietin, pharmacologic inhibition of HIF-alpha degradation offers significant potential for the treatment of acute hypoxic injuries and anemia.
Clinical Interest
General Nephrology, Renal Anemia and Renal Metabolism.
Publications
- Haase, VH Mechanisms of Hypoxia Responses in Renal Tissue. J Am Soc Nephrol, 2013.
- Haase, VH Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev, 2013.
- Grenz, A, Bauerle, JD, Dalton, JH, Ridyard, D, Badulak, A, Tak, E, McNamee, EN, Clambey, E, Moldovan, R, Reyes, G, Klawitter, J, Ambler, K, Magee, K, Christians, U, Brodsky, KS, Ravid, K, Choi, DS, Wen, J, Lukashev, D, Blackburn, MR, Osswald, H, Coe, IR, Nürnberg, B, Haase, VH, Xia, Y, Sitkovsky, M, Eltzschig, HK Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice. J Clin Invest, 122(2), 693-710, 2012.
- Liu, Q, Davidoff, O, Niss, K, Haase, VH Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis. J Clin Invest, 122(12), 4635-44, 2012.
- Haase, VH Hypoxia-inducible factor signaling in the development of kidney fibrosis. Fibrogenesis Tissue Repair, 5 Suppl 1S16, 2012.
- Kobayashi, H, Gilbert, V, Liu, Q, Kapitsinou, PP, Unger, TL, Rha, J, Rivella, S, Schlöndorff, D, Haase, VH Myeloid cell-derived hypoxia-inducible factor attenuates inflammation in unilateral ureteral obstruction-induced kidney injury. J Immunol, 188(10), 5106-15, 2012.
- Kapitsinou, PP, Jaffe, J, Michael, M, Swan, CE, Duffy, KJ, Erickson-Miller, CL, Haase, VH Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury. Am J Physiol Renal Physiol, 302(9), F1172-9, 2012.
- Park, SW, Kim, M, Kim, JY, Brown, KM, Haase, VH, D''Agati, VD, Lee, HT Proximal tubule sphingosine kinase-1 has a critical role in A1 adenosine receptor-mediated renal protection from ischemia. Kidney Int, 82(8), 878-91, 2012.
- Haase, VH Renal cancer: oxygen meets metabolism. Exp Cell Res, 318(9), 1057-67, 2012.
- Gurley, SB, Riquier-Brison, AD, Schnermann, J, Sparks, MA, Allen, AM, Haase, VH, Snouwaert, JN, Le, TH, McDonough, AA, Koller, BH, Coffman, TM AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure. Cell Metab, 13(4), 469-75, 2011.
- Haase, VH Angiotensin II: breathtaking in the renal medulla. Kidney Int, 79(3), 269-71, 2011.
- Kapitsinou, PP, Liu, Q, Unger, TL, Rha, J, Davidoff, O, Keith, B, Epstein, JA, Moores, SL, Erickson-Miller, CL, Haase, VH Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia. Blood, 116(16), 3039-48, 2010 (see commentary by Terry Lappin in the same issue of Blood, see commentary in Kidney International - Journal Club: 78 (8), 717–718, 2010. doi:10.1038/ki.2010.34) .
- Bajwa, A, Jo, SK, Ye, H, Huang, L, Dondeti, KR, Rosin, DL, Haase, VH, Macdonald, TL, Lynch, KR, Okusa, MD Activation of sphingosine-1-phosphate 1 receptor in the proximal tubule protects against ischemia-reperfusion injury. J Am Soc Nephrol, 21(6), 955-65, 2010.
- Weidemann, A, Krohne, TU, Aguilar, E, Kurihara, T, Takeda, N, Dorrell, MI, Simon, MC, Haase, VH, Friedlander, M, Johnson, RS Astrocyte hypoxic response is essential for pathological but not developmental angiogenesis of the retina. Glia, 58(10), 1177-85, 2010.
- Bielesz, B, Sirin, Y, Si, H, Niranjan, T, Gruenwald, A, Ahn, S, Kato, H, Pullman, J, Gessler, M, Haase, VH, Susztak, K Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest, 120(11), 4040-54, 2010.
- Kapitsinou, PP, Haase, VH HO-1 in control of a self-eating kidney. J Am Soc Nephrol, 21(10), 1600-2, 2010.
- Lee, JJ, Natsuizaka, M, Ohashi, S, Wong, GS, Takaoka, M, Michaylira, CZ, Budo, D, Tobias, JW, Kanai, M, Shirakawa, Y, Naomoto, Y, Klein-Szanto, AJ, Haase, VH, Nakagawa, H Hypoxia activates the cyclooxygenase-2-prostaglandin E synthase axis. Carcinogenesis, 31(3), 427-34, 2010.
- Haase, VH Hypoxic regulation of erythropoiesis and iron metabolism. Am J Physiol Renal Physiol, 299(1), F1-13, 2010.
- Welford, SM, Dorie, MJ, Li, X, Haase, VH, Giaccia, AJ Renal oxygenation suppresses VHL loss-induced senescence that is caused by increased sensitivity to oxidative stress. Mol Cell Biol, 30(19), 4595-603, 2010.
- Hao, CM, Haase, VH Sirtuins and their relevance to the kidney. J Am Soc Nephrol, 21(10), 1620-7, 2010.
- Wei, Q, Bhatt, K, He, HZ, Mi, QS, Haase, VH, Dong, Z Targeted deletion of Dicer from proximal tubules protects against renal ischemia-reperfusion injury. J Am Soc Nephrol, 21(5), 756-61, 2010.
- Haase, VH The sweet side of HIF. Kidney Int, 78(1), 10-3, 2010.
- Seagroves, TN, Peacock, DL, Liao, D, Schwab, LP, Krueger, R, Handorf, CR, Haase, VH, Johnson, RS VHL deletion impairs mammary alveologenesis but is not sufficient for mammary tumorigenesis. Am J Pathol, 176(5), 2269-82, 2010.
- Rankin, EB, Rha, J, Selak, MA, Unger, TL, Keith, B, Liu, Q, Haase, VH Hypoxia-inducible factor 2 regulates hepatic lipid metabolism. Mol Cell Biol, 29(16), 4527-38, 2009 (cover page feature).
- Haase, VH Oxygen regulates epithelial-to-mesenchymal transition: insights into molecular mechanisms and relevance to disease. Kidney Int, 76(5), 492-9, 2009.
- Haase, VH Pathophysiological Consequences of HIF Activation. Ann N Y Acad Sci, 117757-65, 2009.
- Haase, VH The VHL tumor suppressor: master regulator of HIF. Curr Pharm Des, 15(33), 3895-903, 2009.
- Weidemann, A, Kerdiles, YM, Knaup, KX, Rafie, CA, Boutin, AT, Stockmann, C, Takeda, N, Scadeng, M, Shih, AY, Haase, VH, Simon, MC, Kleinfeld, D, Johnson, RS The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice. J Clin Invest, 119(11), 3373-83, 2009.
- Boutin, AT, Weidemann, A, Fu, Z, Mesropian, L, Gradin, K, Jamora, C, Wiesener, M, Eckardt, KU, Koch, CJ, Ellies, LG, Haddad, G, Haase, VH, Simon, MC, Poellinger, L, Powell, FL, Johnson, RS Epidermal sensing of oxygen is essential for systemic hypoxic response. Cell, 133(2), 223-34, 2008.
- Haase, VH Hemoglobin in the kidney: breaking with traditional dogma. J Am Soc Nephrol, 19(8), 1440-1, 2008.
- Shah, YM, Ito, S, Morimura, K, Chen, C, Yim, SH, Haase, VH, Gonzalez, FJ Hypoxia-inducible factor augments experimental colitis through an MIF-dependent inflammatory signaling cascade. Gastroenterology, 134(7), 2036-48, 2048.e1-3, 2008.
- Higgins, DF, Kimura, K, Iwano, M, Haase, VH Hypoxia-inducible factor signaling in the development of tissue fibrosis. Cell Cycle, 7(9), 1128-32, 2008.
- Rankin, EB, Rha, J, Unger, TL, Wu, CH, Shutt, HP, Johnson, RS, Simon, MC, Keith, B, Haase, VH Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice. Oncogene, 27(40), 5354-8, 2008.
- Maltzman, JS, Haase, VH Low oxygen stimulates the immune system. Kidney Int, 73(7), 797-9, 2008.
- Peng, M, Falk, MJ, Haase, VH, King, R, Polyak, E, Selak, M, Yudkoff, M, Hancock, WW, Meade, R, Saiki, R, Lunceford, AL, Clarke, CF, Gasser, DL Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease. PLoS Genet, 4(4), e1000061, 2008.
- Kimura, K, Iwano, M, Higgins, DF, Yamaguchi, Y, Nakatani, K, Harada, K, Kubo, A, Akai, Y, Rankin, EB, Neilson, EG, Haase, VH, Saito, Y Stable expression of HIF-1alpha in tubular epithelial cells promotes interstitial fibrosis. Am J Physiol Renal Physiol, 295(4), F1023-9, 2008.
- Kapitsinou, PP, Haase, VH The VHL tumor suppressor and HIF: insights from genetic studies in mice. Cell Death Differ, 15(4), 650-9, 2008.
- Brukamp, K, Jim, B, Moeller, MJ, Haase, VH Hypoxia and podocyte-specific Vhlh deletion confer risk of glomerular disease. Am J Physiol Renal Physiol, 293(4), F1397-407, 2007.
- Higgins, DF, Kimura, K, Bernhardt, WM, Shrimanker, N, Akai, Y, Hohenstein, B, Saito, Y, Johnson, RS, Kretzler, M, Cohen, CD, Eckardt, KU, Iwano, M, Haase, VH Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest, 117(12), 3810-20, 2007.
- Rankin, EB, Biju, MP, Liu, Q, Unger, TL, Rha, J, Johnson, RS, Simon, MC, Keith, B, Haase, VH Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest, 117(4), 1068-77, 2007.
- Blouw, B, Haase, VH, Song, H, Bergers, G, Johnson, RS Loss of vascular endothelial growth factor expression reduces vascularization, but not growth, of tumors lacking the Von Hippel-Lindau tumor suppressor gene. Oncogene, 26(31), 4531-40, 2007.
- Peyssonnaux, C, Zinkernagel, AS, Schuepbach, RA, Rankin, E, Vaulont, S, Haase, VH, Nizet, V, Johnson, RS Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest, 117(7), 1926-32, 2007.
- Wang, Y, Wan, C, Deng, L, Liu, X, Cao, X, Gilbert, SR, Bouxsein, ML, Faugere, MC, Guldberg, RE, Gerstenfeld, LC, Haase, VH, Johnson, RS, Schipani, E, Clemens, TL The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest, 117(6), 1616-26, 2007.
- Park, SK, Haase, VH, Johnson, RS von Hippel Lindau tumor suppressor regulates hepatic glucose metabolism by controlling expression of glucose transporter 2 and glucose 6-phosphatase. Int J Oncol, 30(2), 341-8, 2007.
- Wang, J, Biju, MP, Wang, MH, Haase, VH, Dong, Z Cytoprotective effects of hypoxia against cisplatin-induced tubular cell apoptosis: involvement of mitochondrial inhibition and p53 suppression. J Am Soc Nephrol, 17(7), 1875-85, 2006.
- Haase, VH Hypoxia-inducible factors in the kidney. Am J Physiol Renal Physiol, 291(2), F271-81, 2006.
- Ding, M, Cui, S, Li, C, Jothy, S, Haase, V, Steer, BM, Marsden, PA, Pippin, J, Shankland, S, Rastaldi, MP, Cohen, CD, Kretzler, M, Quaggin, SE Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly progressive glomerulonephritis in mice. Nat Med, 12(9), 1081-7, 2006.
- Rankin, EB, Tomaszewski, JE, Haase, VH Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor. Cancer Res, 66(5), 2576-83, 2006.
- Liu, Y, Pop, R, Sadegh, C, Brugnara, C, Haase, VH, Socolovsky, M Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo. Blood, 108(1), 123-33, 2006.
- Haase, VH The VHL/HIF oxygen-sensing pathway and its relevance to kidney disease. Kidney Int, 69(8), 1302-7, 2006.
- Tang, N, Mack, F, Haase, VH, Simon, MC, Johnson, RS pVHL function is essential for endothelial extracellular matrix deposition. Mol Cell Biol, 26(7), 2519-30, 2006.
- Mack, FA, Patel, JH, Biju, MP, Haase, VH, Simon, MC Decreased growth of Vhl-/- fibrosarcomas is associated with elevated levels of cyclin kinase inhibitors p21 and p27. Mol Cell Biol, 25(11), 4565-78, 2005.
- Neumann, AK, Yang, J, Biju, MP, Joseph, SK, Johnson, RS, Haase, VH, Freedman, BD, Turka, LA Hypoxia inducible factor 1 alpha regulates T cell receptor signal transduction. Proc Natl Acad Sci U S A, 102(47), 17071-6, 2005.
- Rankin, EB, Higgins, DF, Walisser, JA, Johnson, RS, Bradfield, CA, Haase, VH Inactivation of the arylhydrocarbon receptor nuclear translocator (Arnt) suppresses von Hippel-Lindau disease-associated vascular tumors in mice. Mol Cell Biol, 25(8), 3163-72, 2005.
- Karhausen, J, Haase, VH, Colgan, SP Inflammatory hypoxia: role of hypoxia-inducible factor. Cell Cycle, 4(2), 256-8, 2005.
- Biju, MP, Akai, Y, Shrimanker, N, Haase, VH Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxia-induced cell death is glucose dependent. Am J Physiol Renal Physiol, 289(6), F1217-26, 2005.
- Haase, VH The VHL tumor suppressor in development and disease: functional studies in mice by conditional gene targeting. Semin Cell Dev Biol, 16(4-5), 564-74, 2005.
- Pfander, D, Kobayashi, T, Knight, MC, Zelzer, E, Chan, DA, Olsen, BR, Giaccia, AJ, Johnson, RS, Haase, VH, Schipani, E Deletion of Vhlh in chondrocytes reduces cell proliferation and increases matrix deposition during growth plate development. Development, 131(10), 2497-508, 2004.
- Karhausen, J, Furuta, GT, Tomaszewski, JE, Johnson, RS, Colgan, SP, Haase, VH Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest, 114(8), 1098-106, 2004.
- Higgins, DF, Biju, MP, Akai, Y, Wutz, A, Johnson, RS, Haase, VH Hypoxic induction of Ctgf is directly mediated by Hif-1. Am J Physiol Renal Physiol, 287(6), F1223-32, 2004.
- Biju, MP, Neumann, AK, Bensinger, SJ, Johnson, RS, Turka, LA, Haase, VH Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes. Mol Cell Biol, 24(20), 9038-47, 2004.
- Higgins, DF, Lappin, DW, Kieran, NE, Anders, HJ, Watson, RW, Strutz, F, Schlondorff, D, Haase, VH, Fitzpatrick, JM, Godson, C, Brady, HR DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): modulation during epithelial-mesenchymal transition. Kidney Int, 64(6), 2079-91, 2003.
- Cramer, T, Yamanishi, Y, Clausen, BE, Förster, I, Pawlinski, R, Mackman, N, Haase, VH, Jaenisch, R, Corr, M, Nizet, V, Firestein, GS, Gerber, HP, Ferrara, N, Johnson, RS HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell, 112(5), 645-57, 2003.
- Park, SK, Dadak, AM, Haase, VH, Fontana, L, Giaccia, AJ, Johnson, RS Hypoxia-induced gene expression occurs solely through the action of hypoxia-inducible factor 1alpha (HIF-1alpha): role of cytoplasmic trapping of HIF-2alpha. Mol Cell Biol, 23(14), 4959-71, 2003.
- Socolovsky, M, Nam, H, Fleming, MD, Haase, VH, Brugnara, C, Lodish, HF Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts. Blood, 98(12), 3261-73, 2001.
- Haase, VH, Glickman, JN, Socolovsky, M, Jaenisch, R Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor. Proc Natl Acad Sci U S A, 98(4), 1583-8, 2001.
- Snijders, AJ, Ho, SC, Haase, VH, Pillai, S, Bernards, A A lymphocyte-specific Ltk tyrosine kinase isoform is retained in the endoplasmic reticulum in association with calnexin. J Biol Chem, 272(2), 1297-301, 1997.
- Haase VH, Schmidt EV, Wang T, Bernards A "Normal lymphopoiesis in transgenic mice overexpressing the ltk transmembrane tyrosine kinase." Transgenics, (1), 487-95, 1995.
- Haase, VH, Trofatter, JA, MacCollin, M, Tarttelin, E, Gusella, JF, Ramesh, V The murine NF2 homologue encodes a highly conserved merlin protein with alternative forms. Hum Mol Genet, 3(3), 407-11, 1994.
- Trofatter, JA, MacCollin, MM, Rutter, JL, Murrell, JR, Duyao, MP, Parry, DM, Eldridge, R, Kley, N, Menon, AG, Pulaski, K, Haase, VH, Ambrose, CM, Munroe, D, Bove, C, Haines, JL, Martuza, RL, MAcDonald, ME, Seizinger, BR, Short, MP, Buckler, A, Gusella JF A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell, 72(5), 791-800, 1993.
- Snijders, AJ, Haase, VH, Bernards, A Four tissue-specific mouse ltk mRNAs predict tyrosine kinases that differ upstream of their transmembrane segment. Oncogene, 8(1), 27-35, 1993.
- Bernards, A, Haase, VH, Murthy, AE, Menon, A, Hannigan, GE, Gusella, JF Complete human NF1 cDNA sequence: two alternatively spliced mRNAs and absence of expression in a neuroblastoma line. DNA Cell Biol, 11(10), 727-34, 1992.
- Haase, VH, Snijders, AJ, Cooke, SM, Teng, MN, Kaul, D, Le Beau, MM, Bruns, GA, Bernards, A Alternatively spliced ltk mRNA in neurons predicts a receptor with a larger putative extracellular domain. Oncogene, 6(12), 2319-25, 1991.
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