Saleem A. Khan, PhD

My laboratory is studying the roles of microRNAs in HPV-associated cervical and head & neck cancers. We have found that the miRNA expression profiles in HPV-positive squamous cell carcinoma of the head and neck (SCCHN) cell lines and tissues are distinctively different from those of HPV-negative SCCHN and normal oropharyngeal tissue. We have also shown that the E6 oncogene of HPV-16 upregulates the expression of miR-363 and downregulates the expression of miR-218 in HPV-positive SCCHN cell lines. Furthermore, miR-363 is also upregulated in HPV-positive SCCHN tumor tissues. We have also shown previously that the E6 oncogene of high-risk HPVs such as types 16 and 18, but not that of low-risk HPVs such as type 6, downregulates the expression of miR-218 in cervical cancer cells. Our ongoing studies deal with the identification of the mechanisms by which E6 affects miR-363 and miR-218 expression and whether these effects are p53-dependent. We are investigating whether epigenetic processes such as DNA methylation and histone modifications are involved in E6-mediated regulation of these miRNAs. We are also testing whether miR-363 and miR-218 are oncogenic and tumor suppressor miRNAs, respectively, that affect cell proliferation, migration, invasion, adhesion and apoptosis. We are also studying the potential role of miRNAs in aging, using the XFE syndrome as a model system. Using fibroblasts from wild-type and progeroid mice, we have identified several miRNAs whose expression is altered in the ERCC1 progeroid mice. We have also found that the expression of several of these miRNAs is similarly affected in the tissues from the ERCC1 mutant mice. We are currently testing whether the aging-related miRNAs promote cellular senescence. We are also studying the role of PcrA helicase, an essential protein in Gram-positive bacteria, in plasmid replication and cellular DNA metabolism. We have shown that the PcrA helicases of S. aureus, B. anthracis, S. pneumoniae and B. cereus are multifunctional proteins that have ATPase, DNA binding, translocation and helicase activities. Recently, using biochemical and single-molecule approaches we have shown that PcrA blocks homologous DNA recombination in vitro by displacing the RecA protein bound to the DNA. A major current focus of the laboratory is to identify the biochemical activities of PcrA that make it an essential protein in S. aureus.

Lab Personnel

Dr. Parvez Akhtar, Research Associate
Celia Munko, Senior Research Specialist

Areas of Interest

Role of microRNAs in human papillomavirus-associated cancers & in aging; PcrA helicase