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

Oxygen logo Volker H Haase Laboratory

The laboratory of Professor Volker Haase studies hypoxia response pathways and their therapeutic applications in erythropoiesis and iron metabolismkidney 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 renal epithelium

Mitochondria in renal epithelium

Epo RNA-FISH Volker Haase Lab

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

Overwiew of oxygen metabolism in renal tissue

Mechanisms of Renal Hypoxia

Volker Haase Lab - HIF in fatty acid metabolism; Rankin MCB 2009

HIF activation in hepatocytes results in fatty livers

Haase Lab in 2017

Lab news and international meetings

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

Welcome our new lab member Belinda Li

July 2019

Dr. Belinda Li received her M.D. from the State University of New York (SUNY) Downstate College of Medicine. She completed her Urology residency at Loyola University in Chicago, IL and currently is a fellow in Pediatric Urology. Dr. Li works with Drs. Clayton and Tong on the role of hypoxia and HIF signaling in bladder injury and inflammation. Welcome to the Haase lab.

for information on current Haase group members and alumni click here

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.  >

Phase II study on HIF-PHI vadadustat in hemodialysis patients

April 2018

Erythropoiesis-stimulating agents (ESAs) can correct anemia in chronic kidney disease (CKD) but are associated with increased risks of cardiovascular events. Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain (HIF-PHD) dioxygenases, is an oral investigational agent in development for the treatment of anemia in patients with CKD. In a 16-week, open-label, multicenter, Phase 2 trial, Haase and colleagues evaluated vadadustat in 94 patients receiving maintenance hemodialysis previously maintained on ESA therapy. >

link to erythropoiesis, iron metabolism and renal anemia

link to media files on renal anemia

The Haase lab will present at the Keystone meeting on hypoxia and HIF responses, Keystone, CO

Hypoxia: Molecules, Mechanisms and Disease

January 19-23, 2020

Scientific Organizers: José López-Barneo, Sarah R. Walmsley, Hesham A. Sadek and Jacques Pouysségur

Doug Clayton, Nan Guan, Hanako Kobayashi and Andres Urrutia will each present their work on HIF and mitochondrial signaling in kidney, bladder and brain.

for preliminary program information please click here