Albert R. Cunningham, Ph. D.
Associate Professor of Medicine
Clinical Translational Research Building, Room 222
University of Louisville
505 S. Hancock St.
Louisville, KY 40202, USA
- Member, James Graham Brown Cancer Center
- Institute for Molecular Diversity & Drug Design
- Associate Member, Department of Pharmacology and Toxicology
- B.S., Biology, Slippery Rock University of Pennsylvania, 1990
- B.A., Philosophy, Slippery Rock University of Pennsylvania, 1990
- Ph.D., Environmental and Occupational Health, University of Pittsburgh, 1998
Laboratory Team Members:
- Shahid Qamar - Research Associate
- Alex Carrasquer - Post doc
- Huihui Wo - Graduate student
- Naureen Malik - Undergraduate researcher
- Chris George - High school researcher
- Sophia Mahmood - High school researcher
Our individual and public health and the well-being of our economy are dependent upon the extraordinary properties of chemicals. However, while many synthetic and natural chemicals have been beneficial to society, some have proven to be harmful to humans and the environment.
From a toxicological point-of-view, the majority of chemicals in use today only have basic toxicological information associated with them and only a few have been adequately studied for their involvement in complex human and environmental health concerns such as cancer, birth defects, and ecosystem damage. Due to time and cost constraints, accepted methods of toxicity testing cannot adequately assess the existing tens of thousands of chemicals for adverse human and environmental effects.
From a pharmacological point-of-view, many chemicals have therapeutic activity but also have deleterious activity. The identification of novel compounds and the subsequent synthesis of many analogs is often required to maximize efficacy and minimize toxicity. However, in many instances even though the therapeutic target is known, the toxicological targets are not. Thus, even at the cost of excessive safety testing, the toxic effects of some drugs are only realized after widespread use.
To address these points, the Cunningham lab continues to explore the toxicological and pharmacological activity of chemicals through computational structure-activity relationship (SAR) modeling. Specifically, our lab has focused on chemical carcinogenesis, breast cancer, endocrine disrupting chemicals, and anticancer agents.
Recent work entails the development of predictive and mechanistic models for chemicals that may induce cancer but are not directly damaging to DNA. These are a particularly difficult class of carcinogens to identify since they likely do not attack a specific or unique target and therefore are not amicable to most standardized assays for carcinogen determination.
Alternately, for carcinogens that do damage DNA, while this is a significant hallmark for carcinogens, we understand that DNA alone is often not sufficient to result cancer formation. To address this problem, our lab is developing models based on carcinogen-protein interactions for site selective carcinogens with the intent of identifying new molecular targets associated with cancer. Ultimately, while these targets may be useful for identifying unbeknownst carcinogens, it is envisioned that they may have a more significant role as targets for anticancer drug development.
Finally, the decades of large scale testing of chemicals for carcinogen determination has resulted in an important and overlooked result. A significant number of chemicals, when tested for carcinogenicity, actually reduce the number of spontaneous cancers that might otherwise develop in the test animals. These chemicals, therefore, have “anticancer” activity. Since these chemicals were not intended as anticancer drugs but for use as industrial or commercial products, their potential anticancer activity is accompanied by significant toxicity. For these agents, our goal is first to identify and separate the chemical aspects of anticancer activity from toxicity, and then develop a model that is capable of identifying new chemicals with anticancer activity but without significant toxicity.
- Dik S, Ezendam J, Cunningham AR, Carrasquer CA, van Loveren H, et al. Evaluation of in silico models for the identification of respiratory sensitizers. Toxicol Sci. 2014 Dec;142(2):385-94. PubMed PMID: 25239631.
- Carrasquer CA, Batey K, Qamar S, Cunningham AR, Cunningham SL. Structure-activity relationship models for rat carcinogenesis and assessing the role mutagens play in model predictivity. SAR QSAR Environ Res. 2014;25(6):489-506. PubMed PMID: 24697549; NIHMSID: NIHMS764899; PubMed Central PMCID: PMC4830131.
- Kumar P, Carrasquer CA, Carter A, Song ZH, Cunningham AR. A categorical structure-activity relationship analysis of GPR119 ligands. SAR QSAR Environ Res. 2014;25(11):891-903. PubMed PMID: 25401513; NIHMSID: NIHMS738692; PubMed Central PMCID: PMC4795450.
- Cunningham AR, Carrasquer CA, Qamar S, Maguire JM, Cunningham SL, et al. Global structure-activity relationship model for nonmutagenic carcinogens using virtual ligand-protein interactions as model descriptors. Carcinogenesis. 2012 Oct;33(10):1940-5. PubMed PMID: 22678118; PubMed Central PMCID: PMC3463155.
- Carrasquer CA, Malik N, States G, Qamar S, Cunningham SL, Cunningham AR. Chemical structure determines target organ carcinogenesis in rats. SAR QSAR Environ Res. 2012 Oct;23(7-8):775-95. PubMed PMID: 23066888; NIHMSID: NIHMS413662; PubMed Central PMCID: PMC3547634.
- Qamar S, Carrasquer CA, Cunningham SL, Cunningham AR. Anticancer SAR models for MCF-7 and MDA-MB-231 breast cell lines. Anticancer Res. 2011 Oct;31(10):3247-52. PubMed PMID: 21965732.
- Schultz DJ, Wickramasinghe NS, Ivanova MM, Isaacs SM, Dougherty SM, Imbert-Fernandez Y, Cunningham AR, Chen C, Klinge CM. Anacardic acid inhibits estrogen receptor alpha-DNA binding and reduces target gene transcription and breast cancer cell proliferation. Mol Cancer Ther. 2010 Mar;9(3):594-605. PubMed PMID: 20197399; NIHMSID: NIHMS173399; PubMed Central PMCID: PMC2837512.
- Cunningham AR, Carrasquer CA, Mattison DR. A categorical structure-activity relationship analysis of the developmental toxicity of antithyroid drugs. Int J Pediatr Endocrinol. 2009;2009:936154. PubMed PMID: 20111734; PubMed Central PMCID: PMC2810459.
- Cunningham AR, Moss ST, Iype SA, Qian G, Qamar S, et al. Structure-activity relationship analysis of rat mammary carcinogens. Chem Res Toxicol. 2008 Oct;21(10):1970-82. PubMed PMID: 18759503.
- Cunningham, A.R., D.M. Consoer, S.A. Iype, and S.L. Cunningham, A structure‐activity relationship analysis for the identification of environmental estrogens: The categorical‐SAR (cat‐SAR) approach, in Endocrine Disruption Modeling, J. Devillers, Editor. 2009, CRC Press. p. 173‐198
- Cunningham, A.R., S.T. Moss, S.A. Iype, G. Qian, S. Qamar, and S.L. Cunningham, Structure‐activity relationship analysis of rat mammary carcinogens. Chemical Research in Toxicology, 2008. 21: p. 1970‐1982.
- Rosenkranz, H.S., S.L. Cunningham, R. Mermelstein, and A.R. Cunningham, The challenge of testing chemicals for potential carcinogenicity using multiple short term assays. An analysis of a proposed test battery for hair dyes. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2007. 633(1): p. 55‐66.