Carolyn M. Klinge, Ph.D.
Department of Biochemistry & Molecular Genetics
Delia Baxter Building
580 South Preston Street
Louisville, KY 40202
Email Dr. Klinge
The Cancer RIG led by Dr. Carolyn M. Klinge, includes Drs. Chendil Damodaran, Jonathan Freedman (ITEMFC director), David Hein, Shesh Rai (BIFC director), Mark Rothstein, Chris States (CIEHS Director), Sandra Wise and Qungwei Zhang. Drs. Damodaran and Freedman have a MPI grant to investigate mechanisms of cadmium-induced prostate carcinogenesis. This project is a paradigm of collaboration between investigators with widely divergent expertise: Dr. Damodaran in prostate cancer biology and Dr. Freedman in cadmium toxicology. Their recent results show that Cd induced autophagy that promotes transformation1, 2. Dr. J. Wise investigates disruption of DNA repair as a mechanism of chromium induced lung cancer3-5. Dr. Hein’s major interest is the role of N-acetyltransferase 1 in breast carcinogenesis. His group, with collaboration of Dr. States, is revealing a role for this enzyme in carcinogenesis that is not linked to its role in carcinogen activation6-8. Dr. Rai collaborates with many investigators in cancer research. He has developed statistical methods for identifying patterns circulating miRNAs as biomarkers of cancer. He also provides statistical and informatics support for Dr. States’ grants. Dr. Rothstein is a nationally recognized expert in ethical, legal and social issues (ELSI)9-11. He is currently funded to address ELSI associated with use of mobile phone technology to collect individual data. Dr. States is currently funded to investigate mechanisms of dysregulation of miRNA expression in arsenic-induced skin carcinogenesis12-14. Dr. J. Wise investigates disruption of DNA repair as a mechanism of chromium induced lung cancer3-5. Dr. S. Wise investigates dysregulation of apoptosis in chromium-induced lung cancer15-17. Dr. Q. Zhang investigates carcinogenic mechanisms of nickel and cobalt18, 19. Thus, the Cancer RIG investigates the role of several carcinogenic agents in multiple tissues, as well as social ramifications of technology in data collection.
1. Kolluru V, Pal D, Papu John AMS, Ankem MK, Freedman JH and Damodaran C. Induction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis. Cancer Lett. 2017;408:121-129.
2. Pal D, Suman S, Kolluru V, Sears S, Das TP, Alatassi H, Ankem MK, Freedman JH and Damodaran C. Inhibition of autophagy prevents cadmium-induced prostate carcinogenesis. Br J Cancer. 2017;117:56-64.
3. Browning CL, Qin Q, Kelly DF, Prakash R, Vanoli F, Jasin M and Wise JP, Sr. Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells. Toxicol Sci. 2016;153:70-8.
4. Browning CL and Wise JP, Sr. Prolonged exposure to particulate chromate inhibits RAD51 nuclear import mediator proteins. Toxicol Appl Pharmacol. 2017;331:101-107.
5. Holmes AL, Joyce K, Xie H, Falank C, Hinz JM and Wise JP, Sr. The impact of homologous recombination repair deficiency on depleted uranium clastogenicity in Chinese hamster ovary cells: XRCC3 protects cells from chromosome aberrations, but increases chromosome fragmentation. Mutat Res. 2014;762:1-9.
6. Carlisle SM, Trainor PJ, Yin X, Doll MA, Stepp MW, States JC, Zhang X and Hein DW. Untargeted polar metabolomics of transformed MDA-MB-231 breast cancer cells expressing varying levels of human arylamine N-acetyltransferase 1. Metabolomics. 2016;12.
7. Stepp MW, Doll MA, Carlisle SM, States JC and Hein DW. Genetic and small molecule inhibition of arylamine N-acetyltransferase 1 reduces anchorage-independent growth in human breast cancer cell line MDA-MB-231. Mol Carcinog. 2018;57:549-558.
8. Stepp MW, Doll MA, Samuelson DJ, Sanders MA, States JC and Hein DW. Congenic rats with higher arylamine N-acetyltransferase 2 activity exhibit greater carcinogen-induced mammary tumor susceptibility independent of carcinogen metabolism. BMC Cancer. 2017;17:233.
9. Pereira S, Robinson JO, Peoples HA, Gutierrez AM, Majumder MA, McGuire AL and Rothstein MA. Do privacy and security regulations need a status update? Perspectives from an intergenerational survey. PLoS One. 2017;12:e0184525.
10. Rothstein MA. Reconsidering the duty to warn genetically at-risk relatives. Genet Med. 2018;20:285-290.
11. Rothstein MA, Harrell HL and Marchant GE. Transgenerational epigenetics and environmental justice. Environ Epigenet. 2017;3:dvx011.
12. Al-Eryani L, Waigel S, Jala V, Jenkins SF and States JC. Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite. Toxicol Appl Pharmacol. 2017;331:130-134.
13. Al-Eryani L, Waigel S, Tyagi A, Peremarti J, Jenkins SF, Damodaran C and States JC. Differentially Expressed mRNA Targets of Differentially Expressed miRNAs Predict Changes in the TP53 Axis and Carcinogenesis-Related Pathways in Human Keratinocytes Chronically Exposed to Arsenic. Toxicol Sci. 2018;162:645-654.
14. Siefring ML, Lu D, States JC and Van Hoang M. Rapid onset of multiple concurrent squamous cell carcinomas associated with the use of an arsenic-containing traditional medicine for chronic plaque psoriasis. BMJ Case Rep. 2018;2018.
15. Wise SS, Holmes AL, Ketterer ME, Hartsock WJ, Fomchenko E, Katsifis S, Thompson WD and Wise JP, Sr. Chromium is the proximate clastogenic species for lead chromate-induced clastogenicity in human bronchial cells. Mutat Res. 2004;560:79-89.
16. Wise SS, Holmes AL, Liou L, Adam RM and Wise JP, Sr. Hexavalent chromium induces chromosome instability in human urothelial cells. Toxicol Appl Pharmacol. 2016;296:54-60.
17. Wise SS, Wise C, Xie H, Guillette LJ, Jr., Zhu C, Wise JP, Jr. and Wise JP, Sr. Hexavalent chromium is cytotoxic and genotoxic to American alligator cells. Aquat Toxicol. 2016;171:30-6.
18. Wan R, Mo Y, Chien S, Li Y, Li Y, Tollerud DJ and Zhang Q. The role of hypoxia inducible factor-1alpha in the increased MMP-2 and MMP-9 production by human monocytes exposed to nickel nanoparticles. Nanotoxicology. 2011;5:568-82.
18. Wan R, Mo Y, Zhang Z, Jiang M, Tang S and Zhang Q. Cobalt nanoparticles induce lung injury, DNA damage and mutations in mice. Part Fibre Toxicol. 2017;14:38.