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
 

Dohun Pyeon

Assistant Professor PhD


Dohun Pyeon, Ph.D., earned his doctoral degree from the University of Wisconsin- Madison in 1999. He completed postdoctoral research training at Harvard Medical School and the University of Wisconsin-Madison in the laboratories of Drs. Paul Ahlquist and Paul Lambert.

Dr. Pyeon joined the faculty of the University of Colorado School of Medicine Department of Microbiology in 2008.

Human papillomaviruses (HPVs) are small DNA viruses causally associated with a growing number of human cancers, including cervical, vaginal, penile, anal, head/neck, and other squamous cell carcinomas. HPV infections cause about half a million deaths worldwide each year.

While a majority of people become infected with HPV, most clear their infections and, of the remaining people with persistent infections, only small fractions develop pre-cancerous lesions and invasive cancers. Our research focuses on understanding how HPV interacts with the host factors to establish persistent infection and develop invasive cancers.

1. Establishment of persistent HPV infection

To establish persistent HPV infections, it is necessary for the viral genome to enter into the nucleus and establish its genome as a nuclear plasmid for long-term replication. Various host defense mechanisms are believed to play important roles for blocking and/or modulating the early establishment of HPV infections. These host mechanisms may include 1) physical barriers in virus trafficking through the cytoplasm and into the nucleus; 2) direct elimination of virus by host cell scavenger machinery such as autophagosomes; and 3) interference with viral gene expression and replication by host innate immunity. Using HPV16 virions produced by our HiP technology, we recently found that HPV early infection requires cell cycle progression through mitosis for entry of HPV DNA into the nucleus and induces innate immune responses through toll-like receptors. Now, we are developing live imaging systems that track the movement of HPV DNA into the nucleus where productive viral gene expression and replication commence, using genetically engineered HPV DNAs containing fluorescent labels. Further understanding of the mechanisms by which these HPV inhibitors intervene will provide valuable knowledge for development of new drugs against HPV infection.

2. HPV-associated cancer progression

Initiated by HPV, HPV-associated cancers progress through a series of histopathologically characterized cytologic abnormalities (low-grade and high-grade intraepithelial lesions) to invasive cancer. To understand the molecular changes associated with each step in the progressive disease leading to invasive cancer, we have developed and performed functional genomics analyses of patient tissue specimens, from primary human cervical and head/neck tumor, precancerous or normal tissue. These studies revealed that each stage in the progressive disease is associated with a unique pattern of changes in gene expression. Genes upregulated specifically in early lesions were primarily associated with DNA replication/repair and cell proliferation. Interestingly, expression of markers in the IL-8 signaling pathway, which triggers chemotaxis and angiogenesis, differed only between low- and high-grade lesions. By far the greatest number of differences in gene expression was found between high-grade lesion and cancer, which included elevated levels of genes in the actin cytoskeleton signaling, fibrosis, tight junction, leukocyte extravasation, p38 MAP kinase, and vascular endothelial growth factor pathways. To better understand the underlying mechanisms and genetic determinants of cervical cancer progression, we are further 1) identifying host factors/pathways that contribute to cancer progression and 2) developing key targets for treatment of HPV-associated cancers and novel biomarkers for diagnosis and prognosis.

Dr. Pyeon received  the David Geffen Research Fellowship for AIDS Research during his postdoctoral training at Harvard Medical School.  In 2009 he received the Best Poster Award (1st place) from the International Papillomavirus Conference in Sweden.