Hypoxia Responses in Physiology and Pathogenesis

Changes in tissue oxygen levels occur under physiological and pathological conditions. The laboratory of Volker Haase studies hypoxia response pathways and their therapeutic applications.

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Volker Haase Lab

The laboratory of Professor Volker Haase studies hypoxia response pathways in erythropoiesis and iron metabolism, acute and chronic kidney injury, and tumorigenesis. A major focus of the lab is on the interplay between hypoxia signaling, metabolism and cellular differentiation and its regulation by the prolyl hydroxylase domain (PHD) / hypoxia-inducible factor (HIF) / von Hippel-Lindau tumor suppressor (VHL) signaling axis. Haase group members take advantage of powerful cutting-edge mouse genetics, biochemical, metabolomic and single cell approaches to study oxygen and mitochondrial metabolism in kidney, urologic and other diseases. Click on links for information about career opportunities in the Haase lab and publications.

Mitochondria renal epithelium

Mitochondria in renal epithelium

Epo RNA-FISH Volker Haase Lab

Erythropoietin-producing cells in the kidney (red)

Overwiew of oxygen metabolism in renal tissue

Mechanisms of Renal Hypoxia

Epithelial progenitor cells in the developing kidney

Haase Lab in 2017

Lab News and Updates

original research

Respirometry in intact kidney slices

Congratulations to Ryoichi Bessho on the acceptance of his manuscript in AJP Renal.

October 2025

Regional metabolic analysis of structurally preserved kidney slices by ex vivo respirometry

A comprehensive spatial analysis of kidney metabolism is essential for advancing knowledge of both normal kidney physiology and pathophysiology. The kidney exhibits marked regional differences in bioenergetic demands and substrate utilization, reflecting the distinct functional profiles of each nephron segment. To complement existing approaches with freshly isolated tubules or primary cell cultures, we established and validated an ex vivo respirometry method using structurally preserved kidney slices on a Seahorse XFe24 platform. This protocol avoids tissue disruption or enzymatic digestion and enables simultaneous, region-specific measurements of metabolic fluxes in the cortex, outer medulla, and inner medulla. > …
educational resource

American Society of Hematology Educational Program: Update on HIF-PHI Therapy for Anemia in CKD

December 2024

Hypoxia-inducible factor activators: a novel class of oral drugs for the treatment of anemia of chronic kidney disease

Anemia is a hallmark of chronic kidney disease (CKD), worsens with disease progression, and profoundly affects a patient’s well-being. Major pathogenic factors are inadequate kidney erythropoietin (EPO) production and absolute and functional iron deficiency. The 2 mainstays of current anemia treatment are a) replacement therapy with recombinant EPO or 1 of its glycosylated derivatives, administered subcutaneously or intravenously, and b) intravenous (IV) iron injections. Over the past 5 years, hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitors (HIF-PHIs) have been approved in many countries for the management of anemia in both nondialysis and dialysis-dependent patients with CKD.  > …
original research

Mitochondrial electron transport regulates aquaporin-2

Congratulations to Josh Carty, Ryoichi Bessho and team on the acceptance of their manuscript in JCI Insight. In this exciting collaborative study between the Arroyo and Haase labs, we examine the role of oxidative phosphorylation in the regulation of body water homeostasis.

October 2024

Disruption of mitochondrial electron transport impairs urinary concentration via AMPK-dependent suppression of aquaporin-2

Urinary concentration is an energy-dependent process that minimizes body water loss by increasing aquaporin-2 (AQP2) expression in collecting duct (CD) principal cells. To investigate the role of mitochondrial (mt) ATP production in renal water clearance, we disrupted mt electron transport in CD cells by targeting ubiquinone (Q) binding protein QPC (UQCRQ), a subunit of mt complex III essential for oxidative phosphorylation. QPC-deficient mice produced less concentrated urine than controls, both at baseline and after type 2 vasopressin receptor stimulation with desmopressin. Impaired urinary concentration in QPC-deficient mice was associated with reduced total AQP2 protein levels in CD tubules, while AQP2 phosphorylation and membrane trafficking remained unaffected. In cultured inner medullary CD cells treated with mt complex III inhibitor antimycin A, the reduction in AQP2 abundance was associated with activation of  5’ adenosine monophosphate-activated protein kinase (AMPK) and was reversed by treatment with AMPK inhibitor SBI-0206965. > …
announcement

Bessho receives the Sharon Anderson Research Fellowship Award from the American Society of Nephrology

June 2024

Ryoichi Bessho, M.D., Ph.D.

Congratulations to Dr. Ryoichi Bessho, M.D., Ph.D, for receiving the Sharon Anderson Research Fellowship Award as part of the Ben J. Lipps Research Program of the American Society of Nephrology (ASN). Ryoichi trained as an Endocrinologist at Asahikawa Medical University in Japan and joined the Haase lab in 2023. He studies the role of mitochondrial electron transport in kidney physiology and pathogenesis using genetic and single cell approaches. As a graduate student, he made seminal observations regarding the interplay between SGLT2 inhibition and hypoxic signaling in diabetic nephropathy.

announcement

Haase named Fellow of the American Association for the Advancement of Science

April 2024

Volker H. Haase, M.D.

This April, the American Association for the Advancement of Science (AAAS) announced that Volker H. Haase was elected Fellow of the AAAS for his distinguished contributions to the field of experimental and translational medicine, particularly for the development and use of mouse models to study mammalian oxygen sensing in health and disease. This is a great honor for the Haase lab and a reflection of the commitment and hard work of current and former group members.

Click this link to find out more about the seven Vanderbilt faculty members who were elected to the AAAS Fellow class of 2023. “At Vanderbilt, we’re thrilled to celebrate the election of our faculty members as AAAS fellows. It not only highlights our dedication to groundbreaking research and societal impact, but also showcases the inspiration they provide to future generations of scholars,” said C. Cybele Raver, provost and vice chancellor for academic affairs.