Research Interests

Papillomaviruses (PVs) are etiologic agents of a number of benign and malignant tumors of the skin and mucosa.  These include anogenital cancers, such as penile, anal, and cervical carcinomas and adenocarinomas, some cancers of the head-and-neck, and certain non-melanoma skin malignancies. Limited data suggest that HPV might be involved in breast cancers.

The focus of research in our lab is on the early viral infection events as well as the differentiation-dependent life cycles of PVs and how the life cycles are disrupted leading to malignancies. Primarily our group focuses on human papillomaviruses (HPVs), but we also study bovine papillomavirus type 1 (BPV1) as a model system.  Recently, we have begun to establish a rhesus monkey model of papillomavirus-induced genital infection and disease using rhesus papillomavirus type 1 (RhPV1).  This virus causes genital neoplasias and malignancies in rhesus monkeys and we are beginning to use the system to study the pathogenesis of PV-induced anogenital lesions in vivo.

stages

PVs require differentiating epithelium in order to complete their viral life cycles and we use the organotypic (raft) tissue culture system to cultivate differentiating epithelium and study the life cycles of PVs in the laboratory.

A recent advance by our colleagues at the University of Wisconsin-Madison -- the 293T transfection-based high-yield production (HiP) method -- allows us to purify very high titers of infectious PVs (Pyeon, Lambert, and Ahlquist, Proc Natl Acad Sci USA, 102:9311-9316, 2005.)

The long-term goals of our research program are to elucidate the cellular and viral mechanisms that regulate the life cycle of PVs, and to understand the delicate virus-cell interactions that can become unbalanced, leading to malignancy. We are specifically interested in four areas of research with respect to PV infections and cancer:

  1. Investigating the strategies of initial PV replication upon infection and the mechanisms for establishment of viral persistence;
  2. Identifying the step(s) of PV infection at which host range and tissue tropism are demonstrated;
  3. Defining the mechanisms by which PVs are able to affect the differentiation program of the infected epithelial cell;
  4. Analyzing potential common pathways used by various co-factors, which cooperate with HPVs in causing cancers.

 

We have four major areas of funded research (funding source):