Research excellence transforming patient care
Srilata Bagchi, PhD
Professor and Director, Center for the Molecular Biology of Oral Diseases
Our lab's research focuses on better understanding the development of human papillomavirus (HPV) associated cancers at the molecular level. Our analysis involves studies in two different types of HPV-associated cancers, human cervical cancers (>90% contain HPVs) and Oral and Head and Neck cancers, HNSCC (20-30% contain HPVs). We study the functions of two major HPV oncoproteins, E6 and E7 that are expressed in 100% of HPV-associated cancers. We analyze how these viral oncoproteins modify the key cellular tumor suppressor proteins, p53 and Rb to initiate and sustain tumorigenesis. These studies are expected to identify novel targets for therapeutic intervention and might provide new modalities for preventing or treating HPV-related cancers.
Another focus of our lab's research is to study the role of DNA damage and Repair processes in the development of cancer. DNA damage in somatic cells is one of the main causes of aging, cellular senescence, and development of genetic diseases, including cancer. Cells respond to DNA damage by activating repair and the checkpoint pathways. The checkpoint pathways delay the cell cycle to allow for DNA repair. When the extent of damage is overwhelming, the checkpoint pathways direct the cells to undergo permanent arrest or apoptosis. We investigate the damage-sensor function of the damaged DNA binding protein, DDB. DDB is composed to two subunits DDB1 and DDB2. The DDB2 subunit is transcriptionally induced by p53 upon DNA damage, and the function of DDB2 is critical for a sustained activation of the checkpoints following DNA damage In this project, in collaboration with Dr. Pradip Raychaudhuri of the Department of Biochemistry and Molecular Genetics at UIC, we analyze how the DNA damages induced by tobacco metabolites leads to the development of lung cancer and HNSCC.
Roy N, Stoyanova T, Dominguez-Brauer C, Park HJ, Bagchi S, Raychaudhuri P. 2010. DDB2, an essential mediator of premature senescence. Mol Cell Biol.; 30(11):2681-92.
Bagchi S, Raychaudhuri P. 2010. Damaged-DNA Binding Protein-2 Drives Apoptosis Following DNA Damage. Cell Div.; 5:3.
Oh KJ, Kalinina A, Bagchi S. 2010. Destabilization of Rb by human papillomavirus E7 is cell cycle dependent: E2-25K is involved in the proteolysis. Virology; 396(1):118-24.
Stoyanova T, Roy N, Kopanja D, Raychaudhuri P, Bagchi S. 2009. DDB2 (damaged-DNA binding protein 2) in nucleotide excision repair and DNA damage response. Cell Cycle; 8(24):4067-71.
Pan W, Datta A, Adami GR, Raychaudhuri P, Bagchi S. 2003. P19ARF inhibits the functions of the HPV16 E7 oncoprotein. Oncogene; 22(35):5496-503.
Stoyanova T, Roy N, Kopanja D, Bagchi S.*, Raychaudhuri P*. DDB2 decides cell fate following DNA damage. Proc Natl Acad Sci U S A. 2009 Jun 16. [Epub ahead of print]. *Joint corresponding authors.
Kopanja D, Stoyanova T, Okur MN, Huang E, Bagchi S.*, Raychaudhuri P*. Proliferation defects and genome instability in cells lacking Cul4A. Oncogene. 2009 May 11. [Epub ahead of print] PMID: 19430492. *Joint corresponding authors.
Oh KJ, Kalinina A, Park NH, Bagchi S. 2006. Deregulation of eIF4E: 4E-BP1 in differentiated human papillomavirus-containing cells leads to high levels of expression of the E7 oncoprotein. J Virol 80(14):7079-88.
Bondar T, Kalinina A, Khair L, Kopanja D, Nag A, Bagchi S, Raychaudhuri P. 2006. Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis involving the COP9 signalosome. Mol Cell Biol 26(7):2531-9.
Nag A, Bagchi S, Raychaudhuri P. 2004. Cul4A physically associates with MDM2 and participates in the proteolysis of p53. Cancer Res 64(22):8152-5.
Find out more
- UIC Research Resource Center (RRC)
- UIC Biologic Resource Laboratory (BRL)
- UIC Center for Clinical and Translational Sciences (CCTS)
- Tissue Bank/ Transdisciplinary Pathology
- Chicago Biomedical Consortium
- Library Research Resources and Clinical Tools for Dentistry
- National Institute of Craniofacial and Dental Research