
|
Jianxin You, Ph.D. Assistant Professor of Microbiology
Office Address:
Department of Microbiology
Perelman School of Medicine
University of Pennsylvania
201C Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076
TEL 215-573-6781
LAB 215-573-6040
FAX 215-898-9557
jianyou@mail.med.upenn.edu
RESEARCH SUMMARY
Cervical carcinomas are associated with high-risk type human papillomaviruses
(HPVs) such as HPV-16 and -18. The important cellular events
that caused the HPV-infected cells to develop into invasive tumor do not occur
until many years after the initial infection, supporting that persistent infection
with high-risk HPVs is required for the progression to invasive carcinoma.
Research in our laboratory focuses on understanding the virus-host interactions
that allow high-risk HPV to establish and maintain persistent infection in
host cells.
Papillomaviruses establish persistent latent infection by maintaining the viral
genome as autonomous replicating plasmid (episome) in infected cells. To ensure
the faithful partitioning of replicated viral episomes to daughter cells during
host cell division, the viral E2 protein tethers the viral episomes to host chromosomes
during mitosis. Using the bovine papillomavirus (BPV) as a model system, we have
identified the cellular bromodomain protein Brd4 as the anchor for E2/viral episome
complex on host mitotic chromosomes. However, how the human papillomaviruses
are maintained in host cells during latent infection is less clear.
Our major research goals are: 1) to understand the mechanisms that mediate the
persistent maintenance of HPVs in host cells, 2) to identify novel cellular targets
of this oncogenic DNA tumor virus and to investigate how they regulate papillomavirus
life cycle to achieve viral persistence and malignant progression, and 3) to
investigate how dysfunction of important cellular apparatus hijacked by viral
pathogen could lead to human diseases. Our research integrates biochemistry,
proteomics, cell biology and molecular genetics to study how the molecular interplays
between oncogenic DNA tumor viruses and their host targets contribute to tumorigenesis.
Knowledge on the nature of this virus-host interaction could facilitate the development
of novel therapies for treating high-risk HPV latent infection and associated
human cancers. |