Dr. Tina Crone

Education:

B.S. in Horticulture, Pennsylvania State University
PhD. in Cellular and Molecular Biology, Milton S. Hershey Medical Center 

Courses taught:

Biol 255 lab – Anatomy and Physiology II
Biol 100 – General Biology
Biol 204 – Human Biology 

Areas of specification:

Cell Biology, Physiology, Molecular Biology

Research interests:

My research interest involves the post-transcriptional regulation of DNA-repair genes and how this regulation impacts the early onset of cancer. O⁶-Alkylguanine-DNA Alkyltransferase (MGMT) is a ubiquitously expressed DNA-repair protein that removes adducts from the O⁶ position of guanine, one of the major mutagenic lesions in DNA. If left unrepaired, O⁶-guanine alkylation results in G:C to A:T transitions following DNA replication, resulting in a genetic mutation that my lead to the development of a cancer cell. The early onset of cancer often involves the accumulation of such adducts that escape DNA repair, therefore, down-regulation of MGMT gene expression may hasten cancer progression. The silencing of MGMT activity may be attributed to methylation of CpG islands within the MGMT’s gene’s promoter, which leads to its transcriptional silencing, or post-transcriptional regulation by miRNAs, small noncoding RNA sequences that bind to the 3’ UTR of the transcript and prevent translation. To date, over 2000 miRNAs have been found. Several miRNAs regulating MGMT have been found. Understanding this regulation and identifying additional miRNAs that effect MGMT expression could aid in our knowledge of the early onset of cancer.

PUBLICATIONS:

Xu-Welliver, M., Kanugula, S., Loktionova, N. A., Crone, T. M., and Pegg, A. E., Conserved Residue Lysine-165 is Essential for the Ability of O6-alkylguanine-DNA Alkyltransferase to React with O6-Benzylguanine. Biochem J. 2000 Apr 15;347(Pt 2):527-34. 

Loktionova, N. A., Xu-Welliver, M., Crone, T. M., Kanugula, S., and Pegg, A. E.  Protection of CHO Cells by Mutant Forms of 06-Alkylguanine-DNA Alkyltransferase from Killing by BCNU Plus 06-Benzylguanine or 06-Benzyl-8-Oxoguanine. Biochem. Phar. 58:  1999. 

Crone, T. M., Schalles, S., Benedict, C. M., Pan, W., Ren, L., Loy, S. E., Isom, H., and Clawson, G. A. Growth Inhibition By a Triple Ribozyme Targeted to Repetitive B2 Transcripts. Hepatology, 29:1-12, 1999. 

Clawson, G. A., Schalles, S. L., Wolz, G., Weisz, J., Crone, T. M. and Miranda, G. Q. Focal Altered Compartmentation of Repetitive B2(Alu-like) Sequences in Rat Liver Following Hepatocarcinogen Exposure. Cell Growth and Differentiation. 7:635-646, 1996. 

Crone, T. M., Goodtzova, K. and Pegg, A. E. Amino Acid Residues Affecting the Activity and Stability of Human O6-Alkylguanine-DNA Alkyltransferase. Nucleic Acid Research. 363:15-25, 1996. 

Crone, T. M., Kanugula, S. and Pegg, A. E. Mutations in the Ada O6-Alkylguanine-DNA Alkyltransferase Conferring Sensitivity to Inactivation by O6-Benzylguanine and 2,4-Diamino-6-benzyloxy-5-nitrosopyrimidine. Carcinogenesis. 16:1687-1692, 1995. 

Crone, T. M., Goodtzova, K., Edara, S. and Pegg, A. E. Mutations in Human O6-Alkylguanine-DNA Alkyltransferase Imparting Resistance to O6-Benzylguanine. Cancer Res. 54:6221-6227, 1994. 

Goodtzova, K., Crone, T. M. and Pegg, A.  Activation of Human O6-Alkylguanine-DNA Alkyltransferase by DNA. Biochemistry. 33:8385-8390, 1994. 

Crone, T. M. and Pegg, A. E. A Single Amino Acid Change in Human O6-Alkylguanine-DNA Alkyltransferase Decreasing Sensitivity to Inactivation by O6-Benzylguanine. Cancer Res. 53:4750-4753, 1993.