Volker H. Haase, M.D.

Professor

volker.haase@vanderbilt.edu
Faculty Appointments
Professor of Medicine Professor of Molecular Physiology and BiophysicsProfessor of Cancer BiologyKrick-Brooks Chair in Nephrology
Education
M.D., Johann Wolfgang Goethe University, Frankfurt, Germany
Office Address
Division of Nephrology and Hypertension, Vanderbilt University Medical Center, C-3119A MCN
1161 21st Avenue, So.
Nashville, TN 37232-2372
Research Description
LABORATORY of OXYGEN METABOLISM

The Haase research group has long-standing expertise in the molecular, genetic and metabolic analysis of mammalian hypoxia and hypoxia-inducible factor (HIF)-mediated responses, as well as HIF-related transcriptional biology. Hypoxia-Inducible Factors HIF-1 and HIF-2 are oxygen-sensitive basic helix-loop-helix transcription factors that regulate biological processes, which 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.
HIF activity is controlled by prolyl-4-hydroxylase domain (PHD) enzymes, which function as oxygen sensors that target the a-subunit of HIF for hydroxylation and subsequent proteasomal degradation via the von Hippel-Lindau (VHL)-E3 ubiquitin ligase. These enzymes represent excellent drug targets and several compounds are currently in clinical trials for the treatment of renal anemia (Koury and Haase, Nat Rev Nephrol, 2015).
Initially, the Haase research program started with the generation of the first mouse model for VHL disease, which reproduces clinical manifestations of the disease, such as renal cysts, hemangiomas and polycythemia. As part of this effort, the laboratory has established specific roles for HIF-1 and HIF-2 in the pathogenesis of VHL-associated liver hemangiomas, in the hypoxic induction of hepatic and renal erythropoietin and in the regulation of glucose and fatty acid metabolism.
A main focus of the laboratory is on understanding the molecular and cellular basis of hypoxia responses in the adult kidney and in kidney development. As part of this effort the laboratory have spearheaded studies that established novel molecular links between hypoxia, HIF signaling and the progression of chronic kidney disease. The lab furthermore have spearheaded studies that aim at defining the interplay between alterations in energy metabolism, cellular differentiation and function, cell-cell interactions, inflammation and tissue repair mechanisms. For this the laboratory has developed novel technology that permits spatial high-resolution imaging of metabolites in tissue sections.
Another major research focus is on the role of HIF in the regulation of EPO synthesis in kidney and liver as well as iron metabolism. The Haase laboratory has generated several genetic models of polycythemia and anemia and has contributed to defining HIF’s role in iron metabolism and to the development of drugs (HIF stabilizers) that are currently in clinical trial for the treatment of renal anemia. Specifically, the group has identified HIF-2 as the key regulator of renal EPO synthesis and established that HIF coordinates erythropoiesis with iron metabolism by directly regulating iron uptake and release.
Research Keywords
Cellular and molecular mechanisms of oxygen sensing in health and disease, mouse models, hypoxia, renal anemia, erythropoietin, iron metabolism, mitochondrial metabolism, ischemic kidney injury, fibrosis, von Hippel-Lindau disease, pericytes, microvasculature.
Publications
Kapitsinou PP, Rajendran G, Astleford L, Michael M, Schonfeld MP, Fields T, Shay S, French JL, West J, Haase VH. The Endothelial Prolyl-4-Hydroxylase Domain 2/Hypoxia-Inducible Factor 2 Axis Regulates Pulmonary Artery Pressure in Mice. Mol. Cell. Biol [electronic-print]. 2016 May 5/15/2016; 36(10): 1584-94. PMID: 26976644, PII: MCB.01055-15, DOI: 10.1128/MCB.01055-15, ISSN: 1098-5549.

Kobayashi H, Liu Q, Binns TC, Urrutia AA, Davidoff O, Kapitsinou PP, Pfaff AS, Olauson H, Wernerson A, Fogo AB, Fong GH, Gross KW, Haase VH. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin. J. Clin. Invest [print-electronic]. 2016 May 5/2/2016; 126(5): 1926-38. PMID: 27088801, PII: 83551, DOI: 10.1172/JCI83551, ISSN: 1558-8238.

Farsijani NM, Liu Q, Kobayashi H, Davidoff O, Sha F, Fandrey J, Ikizler TA, O'Connor PM, Haase VH. Renal epithelium regulates erythropoiesis via HIF-dependent suppression of erythropoietin. J. Clin. Invest [print-electronic]. 2016 Apr 4/1/2016; 126(4): 1425-37. PMID: 26927670, PMCID: PMC4811147, PII: 74997, DOI: 10.1172/JCI74997, ISSN: 1558-8238.

Bryant AJ, Carrick RP, McConaha ME, Jones BR, Shay SD, Moore CS, Blackwell TR, Gladson S, Penner NL, Burman A, Tanjore H, Hemnes AR, Karwandyar AK, Polosukhin VV, Talati MA, Dong HJ, Gleaves LA, Carrier EJ, Gaskill C, Scott EW, Majka SM, Fessel JP, Haase VH, West JD, Blackwell TS, Lawson WE. Endothelial HIF signaling regulates pulmonary fibrosis-associated pulmonary hypertension. Am. J. Physiol. Lung Cell Mol. Physiol [print-electronic]. 2016 Feb 2/1/2016; 310(3): L249-62. PMID: 26637636, PII: ajplung.00258.2015, DOI: 10.1152/ajplung.00258.2015, ISSN: 1522-1504.

Kapitsinou PP, Haase VH. Molecular mechanisms of ischemic preconditioning in the kidney. Am. J. Physiol. Renal Physiol [print-electronic]. 2015 Nov 11/15/2015; 309(10): F821-34. PMID: 26311114, PII: ajprenal.00224.2015, DOI: 10.1152/ajprenal.00224.2015, ISSN: 1522-1466.

Haase VH. Inflammation and hypoxia in the kidney: friends or foes?. Kidney Int. 2015 Aug; 88(2): 213-5. PMID: 26230196, PMCID: PMC4534718, PII: ki201589, DOI: 10.1038/ki.2015.89, ISSN: 1523-1755.

Koury MJ, Haase VH. Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat Rev Nephrol [print-electronic]. 2015 Jul; 11(7): 394-410. PMID: 26055355, PMCID: PMC4497972, PII: nrneph.2015.82, DOI: 10.1038/nrneph.2015.82, ISSN: 1759-507X.

Pastor-Soler NM, Sutton TA, Mang HE, Kinlough CL, Gendler SJ, Madsen CS, Bastacky SI, Ho J, Al-Bataineh MM, Hallows KR, Singh S, Monga SP, Kobayashi H, Haase VH, Hughey RP. Muc1 is protective during kidney ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol [print-electronic]. 2015 Jun 6/15/2015; 308(12): F1452-62. PMID: 25925251, PMCID: PMC4469889, PII: ajprenal.00066.2015, DOI: 10.1152/ajprenal.00066.2015, ISSN: 1522-1466.

Haase VH. A breath of fresh air for diabetic nephropathy [editorial]. J. Am. Soc. Nephrol [print-electronic]. 2015 Feb; 26(2): 239-41. PMID: 25183808, PMCID: PMC4310668, PII: ASN.2014080754, DOI: 10.1681/ASN.2014080754, ISSN: 1533-3450.

Kapitsinou PP, Sano H, Michael M, Kobayashi H, Davidoff O, Bian A, Yao B, Zhang MZ, Harris RC, Duffy KJ, Erickson-Miller CL, Sutton TA, Haase VH. Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury. J. Clin. Invest [print-electronic]. 2014 Jun; 124(6): 2396-409. PMID: 24789906, PMCID: PMC4092875, PII: 69073, DOI: 10.1172/JCI69073, ISSN: 1558-8238.

Tak E, Ridyard D, Kim JH, Zimmerman M, Werner T, Wang XX, Shabeka U, Seo SW, Christians U, Klawitter J, Moldovan R, Garcia G, Levi M, Haase V, Ravid K, Eltzschig HK, Grenz A. CD73-dependent generation of adenosine and endothelial Adora2b signaling attenuate diabetic nephropathy. J. Am. Soc. Nephrol [print-electronic]. 2014 Mar; 25(3): 547-63. PMID: 24262796, PMCID: PMC3935577, PII: ASN.2012101014, DOI: 10.1681/ASN.2012101014, ISSN: 1533-3450.

Haase VH. Mechanisms of hypoxia responses in renal tissue. J. Am. Soc. Nephrol [print-electronic]. 2013 Mar; 24(4): 537-41. PMID: 23334390, PII: ASN.2012080855, DOI: 10.1681/ASN.2012080855, ISSN: 1533-3450.

Haase VH. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev [print-electronic]. 2013 Jan; 27(1): 41-53. PMID: 23291219, PMCID: PMC3731139, PII: S0268-960X(12)00084-7, DOI: 10.1016/j.blre.2012.12.003, ISSN: 1532-1681.

Lin Q, Huang Y, Booth CJ, Haase VH, Johnson RS, Celeste Simon M, Giordano FJ, Yun Z. Activation of hypoxia-inducible factor-2 in adipocytes results in pathological cardiac hypertrophy. J Am Heart Assoc. 2013; 2(6): e000548. PMID: 24326162, PMCID: PMC3886757, PII: jah3381, DOI: 10.1161/JAHA.113.000548, ISSN: 2047-9980.

Liu Q, Davidoff O, Niss K, Haase VH. Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis. J. Clin. Invest [print-electronic]. 2012 Dec; 122(12): 4635-44. PMID: 23114598, PMCID: PMC3533545, PII: 63924, DOI: 10.1172/JCI63924, ISSN: 1558-8238.

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 [print-electronic]. 2012 Oct; 82(8): 878-91. PMID: 22695326, PMCID: PMC3443517, PII: ki2012224, DOI: 10.1038/ki.2012.224, ISSN: 1523-1755.

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 [print-electronic]. 2012 May 5/15/2012; 188(10): 5106-15. PMID: 22490864, PMCID: PMC3345098, PII: jimmunol.1103377, DOI: 10.4049/jimmunol.1103377, ISSN: 1550-6606.

Haase VH. Renal cancer: oxygen meets metabolism. Exp. Cell Res [print-electronic]. 2012 May 5/15/2012; 318(9): 1057-67. PMID: 22406000, PMCID: PMC3334413, PII: S0014-4827(12)00102-4, DOI: 10.1016/j.yexcr.2012.02.026, ISSN: 1090-2422.

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 [print-electronic]. 2012 May 5/1/2012; 302(9): F1172-9. PMID: 22262480, PMCID: PMC3362175, PII: ajprenal.00667.2011, DOI: 10.1152/ajprenal.00667.2011, ISSN: 1522-1466.

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 [print-electronic]. 2012 Feb; 122(2): 693-710. PMID: 22269324, PMCID: PMC3266792, PII: 60214, DOI: 10.1172/JCI60214, ISSN: 1558-8238.

Haase VH. Hypoxia-inducible factor signaling in the development of kidney fibrosis. Fibrogenesis Tissue Repair. 2012; 5(Suppl 1): S16. PMID: 23259746, PMCID: PMC3368791, PII: 1755-1536-5-S1-S16, DOI: 10.1186/1755-1536-5-S1-S16, ISSN: 1755-1536.

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. 2011 Apr 4/6/2011; 13(4): 469-75. PMID: 21459331, PMCID: PMC3070917, PII: S1550-4131(11)00088-X, DOI: 10.1016/j.cmet.2011.03.001, ISSN: 1932-7420.

Haase VH. Angiotensin II: breathtaking in the renal medulla. Kidney Int. 2011 Feb; 79(3): 269-71. PMID: 21228800, PMCID: PMC3621768, PII: ki2010434, DOI: 10.1038/ki.2010.434, ISSN: 1523-1755.

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 [print-electronic]. 2010 Nov; 120(11): 4040-54. PMID: 20978353, PMCID: PMC2964979, PII: 43025, DOI: 10.1172/JCI43025, ISSN: 1558-8238.

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 [print-electronic]. 2010 Oct 10/21/2010; 116(16): 3039-48. PMID: 20628150, PMCID: PMC2974609, PII: blood-2010-02-270322, DOI: 10.1182/blood-2010-02-270322, ISSN: 1528-0020.

Hao CM, Haase VH. Sirtuins and their relevance to the kidney. J. Am. Soc. Nephrol [print-electronic]. 2010 Oct; 21(10): 1620-7. PMID: 20595677, PMCID: PMC4527176, PII: ASN.2010010046, DOI: 10.1681/ASN.2010010046, ISSN: 1533-3450.

Kapitsinou PP, Haase VH. HO-1 in control of a self-eating kidney [editorial]. J. Am. Soc. Nephrol [print-electronic]. 2010 Oct; 21(10): 1600-2. PMID: 20829407, PMCID: PMC4530623, PII: ASN.2010080876, DOI: 10.1681/ASN.2010080876, ISSN: 1533-3450.

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 [print-electronic]. 2010 Oct; 30(19): 4595-603. PMID: 20679489, PMCID: PMC2950534, PII: MCB.01618-09, DOI: 10.1128/MCB.01618-09, ISSN: 1098-5549.

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. 2010 Aug; 58(10): 1177-85. PMID: 20544853, PMCID: PMC2993327, DOI: 10.1002/glia.20997, ISSN: 1098-1136.

Haase VH. The sweet side of HIF. Kidney Int. 2010 Jul; 78(1): 10-3. PMID: 20551925, PMCID: PMC3789845, PII: ki2010112, DOI: 10.1038/ki.2010.112, ISSN: 1523-1755.

Haase VH. Hypoxic regulation of erythropoiesis and iron metabolism. Am. J. Physiol. Renal Physiol [print-electronic]. 2010 Jul; 299(1): F1-13. PMID: 20444740, PMCID: PMC2904169, PII: ajprenal.00174.2010, DOI: 10.1152/ajprenal.00174.2010, ISSN: 1522-1466.

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 [print-electronic]. 2010 Jun; 21(6): 955-65. PMID: 20338995, PMCID: PMC2900956, PII: ASN.2009060662, DOI: 10.1681/ASN.2009060662, ISSN: 1533-3450.

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 [print-electronic]. 2010 May; 21(5): 756-61. PMID: 20360310, PMCID: PMC2865746, PII: ASN.2009070718, DOI: 10.1681/ASN.2009070718, ISSN: 1533-3450.

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 [print-electronic]. 2010 May; 176(5): 2269-82. PMID: 20382704, PMCID: PMC2861092, PII: S0002-9440(10)60023-5, DOI: 10.2353/ajpath.2010.090310, ISSN: 1525-2191.

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 [print-electronic]. 2010 Mar; 31(3): 427-34. PMID: 20042640, PMCID: PMC2832548, PII: bgp326, DOI: 10.1093/carcin/bgp326, ISSN: 1460-2180.

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 [print-electronic]. 2009 Nov; 119(11): 3373-83. PMID: 19809162, PMCID: PMC2769183, PII: 39378, DOI: 10.1172/JCI39378, ISSN: 1558-8238.

Haase VH. Pathophysiological Consequences of HIF Activation: HIF as a modulator of fibrosis. Ann. N. Y. Acad. Sci. 2009 Oct; 1177: 57-65. PMID: 19845607, PMCID: PMC4529330, PII: NYAS5030, DOI: 10.1111/j.1749-6632.2009.05030.x, ISSN: 1749-6632.

Haase VH. Oxygen regulates epithelial-to-mesenchymal transition: insights into molecular mechanisms and relevance to disease. Kidney Int [print-electronic]. 2009 Sep; 76(5): 492-9. PMID: 19536078, PMCID: PMC3623274, PII: ki2009222, DOI: 10.1038/ki.2009.222, ISSN: 1523-1755.

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 [print-electronic]. 2009 Aug; 29(16): 4527-38. PMID: 19528226, PMCID: PMC2725738, PII: MCB.00200-09, DOI: 10.1128/MCB.00200-09, ISSN: 1098-5549.

Haase VH. The VHL tumor suppressor: master regulator of HIF. Curr. Pharm. Des. 2009; 15(33): 3895-903. PMID: 19671042, PMCID: PMC3622710, PII: CPD-Volker H. Haase (Kietzman), ISSN: 1873-4286.

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 [print-electronic]. 2008 Oct; 295(4): F1023-9. PMID: 18667485, PMCID: PMC4250235, PII: 90209.2008, DOI: 10.1152/ajprenal.90209.2008, ISSN: 1931-857X.

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 [print-electronic]. 2008 Sep 9/11/2008; 27(40): 5354-8. PMID: 18490920, PMCID: PMC2575082, PII: onc2008160, DOI: 10.1038/onc.2008.160, ISSN: 1476-5594.

Haase VH. Hemoglobin in the kidney: breaking with traditional dogma [editorial]. J. Am. Soc. Nephrol [print-electronic]. 2008 Aug; 19(8): 1440-1. PMID: 18614770, PII: ASN.2008060594, DOI: 10.1681/ASN.2008060594, ISSN: 1533-3450.

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 [print-electronic]. 2008 Jun; 134(7): 2036-48, 2048.e1. PMID: 18439915, PMCID: PMC2533811, PII: S0016-5085(08)00440-X, DOI: 10.1053/j.gastro.2008.03.009, ISSN: 1528-0012.

Higgins DF, Kimura K, Iwano M, Haase VH. Hypoxia-inducible factor signaling in the development of tissue fibrosis. Cell Cycle [print-electronic]. 2008 May 5/1/2008; 7(9): 1128-32. PMID: 18418042, PMCID: PMC3784650, PII: 5804, ISSN: 1551-4005.

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. 2008 Apr 4/18/2008; 133(2): 223-34. PMID: 18423195, PMCID: PMC2849644, PII: S0092-8674(08)00289-4, DOI: 10.1016/j.cell.2008.02.038, ISSN: 1097-4172.

Maltzman JS, Haase VH. Low oxygen stimulates the immune system. Kidney Int. 2008 Apr; 73(7): 797-9. PMID: 18340350, PMCID: PMC3791324, PII: ki200815, DOI: 10.1038/ki.2008.15, ISSN: 1523-1755.

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. 2008 Apr; 4(4): e1000061. PMID: 18437205, PMCID: PMC2291193, DOI: 10.1371/journal.pgen.1000061, ISSN: 1553-7404.

Kapitsinou PP, Haase VH. The VHL tumor suppressor and HIF: insights from genetic studies in mice. Cell Death Differ [print-electronic]. 2008 Apr; 15(4): 650-9. PMID: 18219317, PMCID: PMC3799983, PII: 4402313, DOI: 10.1038/sj.cdd.4402313, ISSN: 1350-9047.

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. 2007 Dec; 117(12): 3810-20. PMID: 18037992, PMCID: PMC2082142, DOI: 10.1172/JCI30487, ISSN: 0021-9738.

Brukamp K, Jim B, Moeller MJ, Haase VH. Hypoxia and podocyte-specific Vhlh deletion confer risk of glomerular disease. Am. J. Physiol. Renal Physiol [print-electronic]. 2007 Oct; 293(4): F1397-407. PMID: 17609290, PII: 00133.2007, DOI: 10.1152/ajprenal.00133.2007, ISSN: 1931-857X.

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 [print-electronic]. 2007 Jul 7/5/2007; 26(31): 4531-40. PMID: 17297464, PII: 1210249, DOI: 10.1038/sj.onc.1210249, ISSN: 0950-9232.

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. 2007 Jul; 117(7): 1926-32. PMID: 17557118, PMCID: PMC1884690, DOI: 10.1172/JCI31370, ISSN: 0021-9738.

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. 2007 Jun; 117(6): 1616-26. PMID: 17549257, PMCID: PMC1878533, DOI: 10.1172/JCI31581, ISSN: 0021-9738.

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. 2007 Apr; 117(4): 1068-77. PMID: 17404621, PMCID: PMC1838939, DOI: 10.1172/JCI30117, ISSN: 0021-9738.

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. 2007 Feb; 30(2): 341-8. PMID: 17203215, ISSN: 1019-6439.

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 [print-electronic]. 2006 Sep; 12(9): 1081-7. PMID: 16906157, PII: nm1460, DOI: 10.1038/nm1460, ISSN: 1078-8956.

Haase VH. Hypoxia-inducible factors in the kidney. Am. J. Physiol. Renal Physiol [print-electronic]. 2006 Aug; 291(2): F271-81. PMID: 16554418, PMCID: PMC4232221, PII: 00071.2006, DOI: 10.1152/ajprenal.00071.2006, ISSN: 1931-857X.

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 [print-electronic]. 2006 Jul; 17(7): 1875-85. PMID: 16762987, PII: ASN.2005121371, DOI: 10.1681/ASN.2005121371, ISSN: 1046-6673.

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 [print-electronic]. 2006 Jul 7/1/2006; 108(1): 123-33. PMID: 16527892, PMCID: PMC1895827, PII: 2005-11-4458, DOI: 10.1182/blood-2005-11-4458, ISSN: 0006-4971.

Tang N, Mack F, Haase VH, Simon MC, Johnson RS. PVHL function is essential for endothelial extracellular matrix deposition. Mol. Cell. Biol. 2006 Apr; 26(7): 2519-30. PMID: 16537898, PMCID: PMC1430327, PII: 26/7/2519, DOI: 10.1128/MCB.26.7.2519-2530.2006, ISSN: 0270-7306.

Haase VH. The VHL/HIF oxygen-sensing pathway and its relevance to kidney disease. Kidney Int. 2006 Apr; 69(8): 1302-7. PMID: 16531988, PII: 5000221, DOI: 10.1038/sj.ki.5000221, ISSN: 0085-2538.

Rankin EB, Tomaszewski JE, Haase VH. Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor. Cancer Res. 2006 Mar 3/1/2006; 66(5): 2576-83. PMID: 16510575, PMCID: PMC3514875, PII: 66/5/2576, DOI: 10.1158/0008-5472.CAN-05-3241, ISSN: 0008-5472.

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 [print-electronic]. 2005 Dec; 289(6): F1217-26. PMID: 16048903, PII: 00233.2005, DOI: 10.1152/ajprenal.00233.2005, ISSN: 1931-857X.

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 [print-electronic]. 2005 Nov 11/22/2005; 102(47): 17071-6. PMID: 16286658, PMCID: PMC1287984, PII: 0506070102, DOI: 10.1073/pnas.0506070102, ISSN: 0027-8424.

Haase VH. The VHL tumor suppressor in development and disease: functional studies in mice by conditional gene targeting. Semin. Cell Dev. Biol [print-electronic]. 2005 Aug; 16(4-5): 564-74. PMID: 15908240, PMCID: PMC3787877, PII: S1084-9521(05)00052-2, DOI: 10.1016/j.semcdb.2005.03.006, ISSN: 1084-9521.

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. 2005 Jun; 25(11): 4565-78. PMID: 15899860, PMCID: PMC1140627, PII: 25/11/4565, DOI: 10.1128/MCB.25.11.4565-4578.2005, ISSN: 0270-7306.

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. 2005 Apr; 25(8): 3163-72. PMID: 15798202, PMCID: PMC1069599, PII: 25/8/3163, DOI: 10.1128/MCB.25.8.3163-3172.2005, ISSN: 0270-7306.

Karhausen J, Haase VH, Colgan SP. Inflammatory hypoxia: role of hypoxia-inducible factor. Cell Cycle [print-electronic]. 2005 Feb; 4(2): 256-8. PMID: 15655360, PII: 1407, ISSN: 1551-4005.

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 [print-electronic]. 2004 Dec; 287(6): F1223-32. PMID: 15315937, PII: 00245.2004, DOI: 10.1152/ajprenal.00245.2004, ISSN: 1931-857X.

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. 2004 Oct; 114(8): 1098-106. PMID: 15489957, PMCID: PMC522241, DOI: 10.1172/JCI21086, ISSN: 0021-9738.

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. 2004 Oct; 24(20): 9038-47. PMID: 15456877, PMCID: PMC517905, PII: 24/20/9038, DOI: 10.1128/MCB.24.20.9038-9047.2004, ISSN: 0270-7306.

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. 2004 May; 131(10): 2497-508. PMID: 15128677, PII: 131/10/2497, DOI: 10.1242/dev.01138, ISSN: 0950-1991.

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. 2003 Dec; 64(6): 2079-91. PMID: 14633130, DOI: 10.1046/j.1523-1755.2003.00306.x, ISSN: 0085-2538.

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. 2003 Jul; 23(14): 4959-71. PMID: 12832481, PMCID: PMC162224, ISSN: 0270-7306.

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. 2003 Mar 3/7/2003; 112(5): 645-57. PMID: 12628185, PMCID: PMC4480774, PII: S0092867403001545, ISSN: 0092-8674.

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. 2001 Dec 12/1/2001; 98(12): 3261-73. PMID: 11719363, ISSN: 0006-4971.

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. 2001 Feb 2/13/2001; 98(4): 1583-8. PMID: 11171994, PMCID: PMC29300, PII: 98/4/1583, DOI: 10.1073/pnas.98.4.1583, ISSN: 0027-8424.

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. 1997 Jan 1/10/1997; 272(2): 1297-301. PMID: 8995435, ISSN: 0021-9258.

Haase VH, Schmidt EV, Wang T, Bernards A. Normal lymphopoiesis in transgenic mice overexpressing the ltk transmembrane tyrosine kinase. Transgenics. 1995; ((1)): 487-95.

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. 1994 Mar; 3(3): 407-11. PMID: 8012352, ISSN: 0964-6906.

Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell. 1993 Nov 11/19/1993; 75(4): 826. PMID: 8242753, PII: 0092-8674(93)90501-G, ISSN: 0092-8674.

Snijders AJ, Haase VH, Bernards A. Four tissue-specific mouse ltk mRNAs predict tyrosine kinases that differ upstream of their transmembrane segment. Oncogene. 1993 Jan; 8(1): 27-35. PMID: 8380920, ISSN: 0950-9232.

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. 1992 Dec; 11(10): 727-34. PMID: 1457041, ISSN: 1044-5498.

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. 1991 Dec; 6(12): 2319-25. PMID: 1662793, ISSN: 0950-9232.

Available Postdoctoral Position Details
Posted: 12/13/2015
NIH-funded postdoctoral position: We are looking for highly motivated applicants, who would like to pursue a career in biomedical science and would like to work in a highly competitive field.  A successful applicant will have not only outstanding technical but also excellent oral communication and writing skills. 

Research projects include:
a) characterization of mouse models of disrupted oxygen sensing,
b) identification, functional and molecular characterization of HIF target genes involved in cellular metabolism and hypoxic injury responses,
c) in vitro and in vivo investigations of HIF signaling in acute and chronic hypoxic injury.

Rotation students will participate in ongoing projects and will be exposed to a broad spectrum of molecular techniques, as well as in vivo work.