Skip to main content
Sign In

The CU School of Medicine is top-ranked in primary care, pediatrics and family and rural medicine. We offer degrees in doctor of medicine, physical therapy, physician assistant, medical science in anesthesiology, genetic counseling, modern human anatomy.

Molecular Biology Program
 

Cheng Hu, Assistant Professor

Ph.D. (1999), Rush University


 

 

 

 

Contact Info:

Molecular Biology
University of Colorado

Cheng Hu, Ph.D.  Research One South
(RC1-South), Room 11103
Cheng-Jun.Hu@ucdenver.edu Phone: 303-724-4576

 

Role of hypoxic response in tumor progression and metastasis

Research Interests: Hypoxic microenvironments are frequently found in solid tumors as a result of an imbalance between oxygen supply and consumption. Tumor hypoxia is a major therapeutic concern since it reduces the effectiveness of radiotherapy and some oxygen-dependent cytotoxic agents. More recently, hypoxia has been shown to be a driving force for malignant progression by hypoxia-inducible factor (HIF)-mediated activation of angiogenesis, anaerobic metabolism, and other processes that enable tumor cells to survive or escape their oxygen-deficient environment. Since this pathway operates in almost all solid malignancies, understanding the function and regulation of HIF will have a broad impact on cancer biology.

Transcriptional responses to hypoxia are primarily mediated by hypoxia inducible factors (HIFs), HIF-1a and HIF-2a. HIF-1a and HIF-2a exhibit several important similarities, however, there is growing evidence indicating that the individual contributions of HIF-1a and HIF-2a in tumor progression are different. To distinguish the role of HIF-1aand HIF-2a in cancer progression, our work has been focusing on these specific areas:

  1. What are the unique and common target genes of HIF-1a and HIF-2a?
  2. What is the individual role of HIF-1a and HIF-2a in cancer progression?
  3. What are the factors controlling HIF transcriptional activity?

We have completed target gene studies, which demonstrated that HIF-1a and HIF-2a have their unique targets (Hu et al., 2003). For example, glycolytic genes are exclusively activated by HIF-1a while HIF-2a uniquely regulates genes involved in angiogenesis (VEGF), cell proliferation (cyclin D1, PDGF, and TGFa) and extracellular matrix metabolism (MMP-2 and PAI-1). These studies suggest a critical role of HIF-2a in tumor progression and metastasis. We are currently deleting or over-expressing HIF-2a in mouse strains that have head-and-neck cancers to investigate the roles of HIF in tumor progression and metastasis.

We determined that HIF-1a and HIF-2a require distinct transcriptional cofactors for their transcriptional activity (Hu et al., 2006). We are investigating the factors that are required for general or promoter-specific transcriptional activity of HIF-1a and HIF-2a. Understanding the interactions between HIF and its cofactors will lay down a foundation to specifically block HIF general transcritpional activity or HIF's regulation of a particular gene.

​​