Projects and Grants per year
Personal profile
Research Interests
Our laboratory focuses on the interrelationships between DNA damage and its repair to human health outcomes, primarily the development of cancer and other age-related diseases. One area of emphasis is the function of the human RecQ helicase enzymes required for maintaining genome stability. Although there are five human RecQ helicases, we primarily investigate the roles of WRN and BLM that are deficient in the premature aging and cancer-prone hereditary diseases Werner and Bloom syndromes, respectively.
Findings from ours and others’ research indicate that WRN and BLM have roles in telomere maintenance and DNA recombination pathways; defects in these pathways result in 1) chromosomal instability that increases cancer susceptibility or 2) cellular senescence and apoptotic cell death that accelerates some tissue-specific aging phenotypes. While WRN has a definite impact on telomere stability, both WRN and BLM are currently also believed to participate in the ability of cells to properly resolve replication stress caused by DNA damage and other circumstances.
Our research is focused on clarifying the specific functions of WRN and BLM in their respective pathways. We are also interested in targeting these pathways to potentially enhance the efficacy of certain cancer chemotherapeutic agents that damage DNA.
Another area of recent study is the investigation into the roles that exposures to specific environmental agents play in increasing cancer susceptibility. Our lab is particularly interested in the effects of metal and tobacco-related exposures on the generation and repair of DNA damage with respect to lung and other cancers. This includes the examination of 1) generation of DNA damage and/or alteration of DNA repair efficiency by specific compounds or complex mixtures, 2) differential repair efficiency of structurally distinct DNA lesions, and 3) relationships between environmental exposures, steady-state DNA damage burdens and cancer development. To this end, our lab has developed assays suitable for measuring and quantifying a broad spectrum of lesions (or subsets thereof) in DNA derived from experimental, clinical, and epidemiological samples.
In collaborations with other researchers here at the University of Kentucky and elsewhere, we are implementing these assays in several scenarios related to cancer susceptibility. A significant portion of this research is centered on possible additional contributing factors that underlie the extremely high incidence of smoking-related lung cancer in Appalachian Kentucky.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
Doctor of Philosophy, University Of North Carolina
1991
Bachelor of Arts, University Of North Carolina
1979
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Collaborations and top research areas from the last five years
Projects & Grants
- 21 Finished
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CCSG Pilot: Targeting the Synthetic Lethal Relationship Between Deficiencies in DNA Mismatch Repair and WRN Helicase to Treat MSI-High Tumors
Goellner, E. (PI), Evers, B. M. (CoI), Orren, D. (CoI), Thorson, J. (CoI), Wu, J. (CoI) & Zaytseva, Y. (CoI)
12/1/19 → 11/30/21
Project: Research project
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Pilot: Center for Appalachian Research in Environmental Sciences: Exposure to E-cigarette Vapor Alters Gene Expression and Induces Inflammatory Responses
Orren, D. (PI), Chen, L. (CoI), Curry, T. (CoI), Hahn, E. (CoI), Machwe, A. (CoI), Pearson, K. (CoI), Swanson, H. (CoI) & Waters, C. (CoI)
National Institute of Environmental Health Sciences
5/1/17 → 3/31/21
Project: Research project
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Pilot: Center for Appalachian Research in Environmental Sciences: Exposure to E-cigarette Vapor Alters Gene Expression and Induces Inflammatory Responses
Orren, D. (PI), Chen, L. (CoI), Curry, T. (CoI), Hahn, E. (CoI), Machwe, A. (CoI), Pearson, K. (CoI), Swanson, H. (CoI) & Waters, C. (CoI)
National Institute of Environmental Health Sciences
5/1/17 → 3/31/22
Project: Research project
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Radon and Tobacco Smoke Exposure Biomarkers of Lung Cancer Risk
Hahn, E. (PI), Fan, W.-M. (CoI), Machwe, A. (CoI), Mullett, T. (CoI), Orren, D. (CoI) & Wang, C. (CoI)
7/1/16 → 12/31/19
Project: Research project
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A randomized phase II trial of induction chemotherapy and low-dose fractionated radiation
Arnold, S. (PI), Izumi, T. (CoI), Kudrimoti, M. (CoI), Machwe, A. (CoI), Orren, D. (CoI), Dressler, E. (Former CoI) & Edwards, D. (Former CoI)
8/1/14 → 7/31/22
Project: Research project
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S6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance
Ganguly, S., Burikhanov, R., Sviripa, V. M., Ellingson, S., Jiang, J., Gosser, C. M., Orren, D., Goellner, E. M., Shenoy, G. G., Rao, M., D’orazio, J., Brainson, C. F., Zhan, C.-G., Spielmann, P. H., Watt, D. & Rangnekar, V. M., 2025, In: International Journal of Biological Sciences. 21, 2, p. 454-472 19 p.Research output: Contribution to journal › Article › peer-review
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Cigarette Smoke-Induced Epithelial-to-Mesenchymal Transition: Insights into Cellular Mechanisms and Signaling Pathways
Alqithami, S. M., Machwe, A. & Orren, D. K., Sep 2024, In: Cells. 13, 17, 1453.Research output: Contribution to journal › Review article › peer-review
Open Access -
Response to Replication Stress and Maintenance of Genome Stability by WRN, the Werner Syndrome Protein
Orren, D. K. & Machwe, A., Aug 2024, In: International Journal of Molecular Sciences. 25, 15, 8300.Research output: Contribution to journal › Review article › peer-review
Open Access1 Scopus citations -
Description of a Lung Cancer Hotspot: Disparities in Lung Cancer Histology, Incidence, and Survival in Kentucky and Appalachian Kentucky
Brainson, C. F., Huang, B., Chen, Q., McLouth, L. E., He, C., Hao, Z., Arnold, S. M., Zinner, R. G., Mullett, T. W., Bocklage, T. J., Orren, D. K., Villano, J. L. & Durbin, E. B., Nov 2021, In: Clinical Lung Cancer. 22, 6, p. e911-e920Research output: Contribution to journal › Article › peer-review
Open Access5 Scopus citations -
A case-control study of trace-element status and lung cancer in Appalachian Kentucky
Unrine, J. M., Slone, S. A., Sanderson, W., Johnson, N., Durbin, E. B., Shrestha, S., Hahn, E. J., Feltner, F., Huang, B., Christian, W. J., Mellon, I., Orren, D. K. & Arnold, S. M., Feb 2019, In: PLoS ONE. 14, 2, e0212340.Research output: Contribution to journal › Article › peer-review
Open Access15 Scopus citations