Elliot Androphy, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Dermatology
   Medicine
   Molecular Genetics and Microbiology

Other Affiliation(s):
   Center for AIDS Research
   Clinical and Population Health Research
   Interdisciplinary Graduate Program
   Program in Immunology and Virology

Pathogenesis of papillomavirus infections

The laboratory studies the pathogenesis of papillomavirus infections, which serve as a model to understand how normal human cells are induced toward cancer.  The E6 and E2 projects involve techniques of cell biology and epithelial cell culture, DNA and RNA manipulation, protein chemistry, yeast genetics, and transgenic animal models.  We also study a common form of muscular dystrophy.  These projects are supported by grants from the NIH.

1. Mechanism of papillomavirus mediated cell transformation and development of cancer
   Papillomaviruses cause warts and cervical cancer, one of the most common malignancies of women in the world.  We are studying how the viral E6 protein transforms and immortalizes human cells and how these relate to activities necessary for viral DNA replication. We are characterizing E6 interacting proteins and, using expression profiling, identifying cellular transcription programs altered by E6.
2. Regulation of transcription and DNA replication
   The E2 protein regulates viral transcription, DNA replication and coordinates viral genome segregation in mitosis. We investigate the cellular factors necessary for these E2 activities.
3. Structure based drug design
   Working with James Baleja Ph.D., a structural biochemist at Tufts Medical School, we use molecular modeling to design novel viral inhibitors.
4. Genetics and pathogenesis of Spinal Muscular Atrophy (SMA)
   SMA is a common form of muscular dystrophy. The deficient protein, SMN, is thought to be involved in biogenesis of mRNA splicing complexes.  We have shown that SMA results from alternative splicing and we seek to define the cellular splicing factors necessary for correct recognition and processing of its mRNA.  High throughput screens seek to identify chemicals and drugs that modulate mRNA processing and restore expression of the SMN protein.

Representative Recent Publications

Baleja J.B., Cherry J., Gao H., Liu Z., Nicklaus M., Voigt J.H., Chen J.J., and Androphy E.J.  Identification of papillomavirus inhibitors based on three-dimension structures of E6-interacting proteins. Antiviral Res. 72:49-59, 2006.

Parish J.L., Rosa J., Wang X., Lahti J.M., Doxsey S., and Androphy E.J. The human DNA helicase hChlR1 is required for sister chromatid cohesion in mammalian cells. J. Cell Sci. 119: 4857-4865, 2006.

Parish J.L., Bean A. M., Park R.B., and Androphy E.J. ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and viral genome maintenance. Molec. Cell, 24:867-876, 2006.

Singh N.K., Singh R.N., and Androphy E.J. Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes. Nucl. Acid. Res. 35: 371-389, 2007.

Yu T., Peng Y-C., and Androphy, E.J. Mitotic kinesin-like protein 2 binds and co-localizes with papillomavirus E2 during mitosis. J. Virol. 81: 1736-1745, 2007.

Ajay Kumar R., Naidu S., Wang X., Imbalzano, A., Androphy E.J. Interaction of papillomavirus E2 protein with the chromatin remodeling Brm complex leads to enhanced transcriptional activation. J. Virol. 81: 2213-2220, 2007.

Potential Rotation Projects

1. Mechanism of cutaneous and breast epithelial cell immortalization induced by the human papillomavirus E6 protein.



2. Characterization of E6 interacting proteins and their requirement for viral replication in keratinocytes.



3. Identification of cellular proteins that bind the papillomavirus E2 and their relationship to E2 functions in regulation of viral transcription, DNA regulation, and mitotic genome segregation.



4. Structure based drug design of E6 and E2 inhibitors.



5. Regulation of mRNA splicing using SMN as a model, including identification of cis acting sequences and trans-acting splicing factors.



6. Biologic screens for compounds that alter SMN slicing and may be used in therapy of Spinal Muscular Atrophy.

Academic / Clinical Background

• Brandeis University, A.B.
• University of Rochester, M.D.
• University of Pittsburgh Health Sciences Center;
  Intern in Medicine;
  Resident in Dermatology
• National Cancer Institute, Medical and Senior Staff Fellow;
  Dermatology Branch and Laboratory of Cellular Oncology

Current Appointments

Barbara and Nathan Greenberg Chair in Biomedical Sciences

Director of the MD/PhD. program

Office: LRB 328
Phone: 508-856-6602
E-mail: Elliot.Androphy@umassmed.edu
Keywords: Cancer Biology, Virology, Gene Expression

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