Koenraad Van Doorslaer

Assistant Professor

Dr. Van Doorslaer received his BS and MS from the University of Leuven, Belgium. He left the land of beer and chocolate to pursue a Ph.D. in the lab of Dr. Robert Burk, at the Albert Einstein College of Medicine in New York. For his post-doctoral work, he joined the lab of Dr. McBride located within the National Institute of Allergy and Infectious Disease at the NIH.

Dr. Van Doorslaer recently joined the faculty of the School of Animal and Comparative Biomedical Sciences at the University of Arizona. He later joined the Immunobiology faculty. Dr. Van Doorslaer also holds appointments within the BIO5 Institute, and the cancer biology and genetics GIDP. His current research combines thorough evolutionary analysis with state-of-the-art molecular techniques to understand why certain DNA viruses are oncogenic. His lab is particularly interested in a subset of human oncogenic papillomaviruses.

The red queen hypothesis states that the host-parasite arms race results in an uneasy balance. Many persistent viruses have co-evolved along-side their hosts for millions of years. Under normal conditions, most persistent viruses do not cause overt disease in the host. Papillomaviruses have evolved to usurp the cellular machinery to complete their life-cycle. The papillomaviral lifecycle perturbs the normal differentiation cycle of the infected cell, forcing cells to divide far beyond their natural lifespan. It is feasible that the continued insult provided by replicating viruses eventually results in malignant transformation of the infected cell. However, while the persistent infection is key to viral oncogenesis, many long-term persisting viruses do not cause cancer. We use cutting-edge technologies and approaches to elucidate which viral phenotypes are associated with oncogenic progression. The pathways targeted by these viruses may represent powerful targets for therapeutic intervention.

Research Interests: 

Evolutionary genomics of papillomavirus cancer

It is improbable that the ability to cause cancer provides papillomaviruses with an evolutionary advantage. It is likely that many of the viral functions linked to oncogenesis were evolutionarily beneficial as papillomavirus adapted to novel environmental niches on the host (e.g., external genitalia vs. cervix). Papillomaviruses have evolved to usurp the cellular machinery to complete their life-cycle. The papillomaviral lifecycle perturbs the normal differentiation cycle of the infected cell, forcing cells to divide far beyond their normal lifespan. It is feasible that the continued insult provided by replicating viruses eventually results in malignant transformation of the infected cell. However, while the persistent infection is key to viral oncogenesis, many long-term persisting viruses do not cause cancer. By carefully interrogating the differences between these viruses, We believe it will be possible to elucidate which viral phenotypes are associated with oncogenic progression. The pathways targeted by these viruses may represent powerful targets for therapeutic intervention.

 

Papillomavirus recombination

Over the span of millions of years, papillomaviruses have evolved to optimize most, if not all, base-pairs of their 8kb genomes. It is, therefore, likely that inter-type recombination will be associated with a loss of viral fitness compared to the parental types. In the absence of some changing environmental factor, this reduced fitness limits the chances of recombinants to become fixed in the population. Indeed, recombination between distinct papillomavirus types has not been an important determinant of the papillomavirus evolutionary history. Based on the evolutionary analysis, the early genes and late genes have evolved as distinct cassettes. Successful, ancient recombination events appear to have combined the regions of the genome coding for the capsid proteins from one parent with the regulatory proteins of the second parent. For the oncogenic viruses, two of these regulatory proteins (E6 and E7) have been shown to be potent oncogenes. This project studies the effects of recombination on viral fitness.

 

Virus metagenomics

Viruses are the most abundant biological entity in every ecosystem. From the ocean to the human skin, viruses are extremely plentiful. We believe that the community dynamics of viruses is essential for the health of an ecosystem. However, measuring these dynamics is complicated. Viruses cannot be cultured in the absence of a host.

Furthermore, viruses do not share genes that are common to all families of viruses. Viral Metagenomic analyses allow us to study which viral communities are present in specific ecosystems. This project is a collaboration with Drs. Arvind Varsani (ASU) and Christopher Buck (NCI).

 

The Papillomavirus episteme (PaVE)

The Papillomavirus Episteme (PaVE) was established in the lab of Alison A. Mcbride at NIAID. PaVE provides highly organized and curated papillomavirus genomics information and tools to the scientific community. We develop tools that interact with or integrate into the PaVE website and databases.