Hypoxia Responses in Physiology and Pathogenesis

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

Volker Haase Lab

The laboratory of Professor Volker Haase studies hypoxia response pathways and their therapeutic applications in erythropoiesis and iron metabolism, kidney injury and ischemic pre-conditioning, inflammation, kidney development 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 recent publications.

Mitochondria in renal epithelium

Erythropoietin-producing cells in the kidney
(red fluorescent signal)

Overwiew of oxygen metabolism in renal tissue

Mechanisms of Renal Hypoxia

Epithelial progenitor cells in the developing kidney

Lab news and updates

Congratulations to Ken Ishii, Hanako Kobayashi, Nan Guan, Carmen Tong, Andraia Li, Olena Davidoff and our collaborators on the acceptance of our paper

October 2020

Renal epithelial TFAM deficiency results in progressive mitochondrial depletion associated with severe cystic disease

More to follow soon.

Congratulations to Andres Urrutia on his new paper in Acta Physiologica

August 2020

Inactivation of HIF-prolyl 4-hydroxylases 1, 2 and 3 in NG2-expressing cells induces HIF2-mediated neurovascular expansion independent of erythropoietin

The study looks at the role of brain pericyte oxygen sensing and erythropoietin in neurovascular homeostasis.

for link to article click here

New insights into the role of glycogen as an energy resource in acute kidney injury

April 2020

A perspective in Kidney International on how renal glycogen metabolism may contribute to cytoprotection afforded by pre-ischemic HIF–prolyl hydroxylase inhibition.

for link to editorial click here

Kyoji Yamaguchi joins the Haase group

November 2019

The Haase lab welcomes Dr. Kyoji Yamaguchi. Dr. Yamaguchi joined the Vanderbilt faculty coming from Japan where he led a drug discovery program in a prominent pharmaceutical company and developed HIF-prolyl hydroxylase inhibitors for the treatment of anemia and chronic kidney disease.

for information on current Haase group members and alumni click here

Review published on current clinical experience with HIF-activators in renal anemia therapy

August 2019

Hypoxia-inducible factor activators in renal anemia: Current clinical experience

Prolyl hydroxylase domain (PHD) oxygen sensors are dioxygenases that regulate the activity of hypoxia-inducible factor (HIF). Small molecule inhibitors of PHD dioxygenases stimulate the production of endogenous EPO and improve iron metabolism resulting in effective anemia management in patients with chronic kidney disease. In this review Volker Haase and Neil Sanghani survey current clinical experience with HIF-PHIs, discuss potential therapeutic advantages and deliberate over safety concerns regarding long-term administration in patients with renal anemia. > …

link to erythropoiesis, iron metabolism and renal anemia

link to media files on renal anemia

Congratulations to our collaborator Mark Boothby on the acceptance of his PNAS paper

April 2019

Hypoxia-inducible factors in CD4+ T cells promote metabolism, switch cytokine secretion, and T cell help in humoral immunity

T cell help in humoral immunity includes interactions of B cells with activated extrafollicular CD4⁺ and follicular T helper (Tfh) cells. Each can promote antibody responses but Tfh cells play critical roles during germinal center (GC) reactions. After restimulation of their antigen receptor (TCR) by B cells, helper T cells act on B cells via CD40 ligand and secreted cytokines that guide Ig class switching. Hypoxia is a normal feature of GC, raising questions about molecular mechanisms governing the relationship between hypoxia response mechanisms and T cell help to antibody responses. > ...