Gregg L. Semenza, M.D., Ph.D.

1. Molecular mechanisms of oxygen homeostasis. The Semenza lab purified, cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. HIF-1 expression increases exponentialåy as cellular O2 concentration declines. HIF-1 activates transcription of genes that are essential for adaptive responses to hypoxia, such as glycolysis, erythropoiesis, angiogenesis, and vascular remodeling. They are presently investigating the molecular mechanisms by which HIF-1 activates transcription of target genes using chromatin immunoprecipitation-mass spectrometry, RNA interference, RNA sequencing and other techniques to identify proteins that are recruited by HIF-1 to hypoxia response elements to activate gene transcription.
2. Role of HIF-1 in cancer. The Semenza lab is investigating the effects of altered HIF-1 activity on tumor growth, metabolism, vascularization, invasion/metastasis, cancer stem cell specification and immune evasion in preclinical models. These studies are providing proof-of-principle that inhibition of HIF-1 activity represents a novel strategy of cancer therapy. The lab identified several drugs that potently inhibit HIF-1 and block cancer progression in mouse models. The lab is utilizing multiple drug discovery strategies to identify novel HIF inhibitors and testing their efficacy in various cancer types.
3. Role of HIF-1 in ocular neovascularization. In collaboration with the laboratory of Dr. Akrit Sodhi at the Wilmer Eye Institute, the Semenza lab is testing novel HIF inhibitors for their efficacy in blocking choroidal and retinal neovascularization in mouse models of blinding eye diseases.
4. Role of HIF-1 in sleep apnea-associated hypertension and impaired glucose homeostasis. In collaboration with the laboratory of Prof. Nanduri Prabhakar at the University of Chicago, the Semenza lab is investigating the role of HIF-1 in activation of the sympathetic nervous system in response to intermittent hypoxemia associated with sleep apnea.

Dr. Semenza’s lab is currently investigating: 

1. Molecular mechanisms of oxygen homeostasis. The Semenza lab purified, cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. HIF-1 expression increases exponentialåy as cellular O2 concentration declines. HIF-1 activates transcription of genes that are essential for adaptive responses to hypoxia, such as glycolysis, erythropoiesis, angiogenesis, and vascular remodeling. They are presently investigating the molecular mechanisms by which HIF-1 activates transcription of target genes using chromatin immunoprecipitation-mass spectrometry, RNA interference, RNA sequencing and other techniques to identify proteins that are recruited by HIF-1 to hypoxia response elements to activate gene transcription.
2. Role of HIF-1 in cancer. The Semenza lab is investigating the effects of altered HIF-1 activity on tumor growth, metabolism, vascularization, invasion/metastasis, cancer stem cell specification and immune evasion in preclinical models. These studies are providing proof-of-principle that inhibition of HIF-1 activity represents a novel strategy of cancer therapy. The lab identified several drugs that potently inhibit HIF-1 and block cancer progression in mouse models. The lab is utilizing multiple drug discovery strategies to identify novel HIF inhibitors and testing their efficacy in various cancer types.
3. Role of HIF-1 in ocular neovascularization. In collaboration with the laboratory of Dr. Akrit Sodhi at the Wilmer Eye Institute, the Semenza lab is testing novel HIF inhibitors for their efficacy in blocking choroidal and retinal neovascularization in mouse models of blinding eye diseases.
4. Role of HIF-1 in sleep apnea-associated hypertension and impaired glucose homeostasis. In collaboration with the laboratory of Prof. Nanduri Prabhakar at the University of Chicago, the Semenza lab is investigating the role of HIF-1 in activation of the sympathetic nervous system in response to intermittent hypoxemia associated with sleep apnea.