Dr. Sulentic is currently an Associate Professor within the Department of Pharmacology and Toxicology at Wright State University, Boonshoft School of Medicine. Prior to joining the faculty at Wright State in November 2003, she was a postdoctoral fellow in the laboratory of Dr. Norbert Kaminski at Michigan State University and was funded under an NIEHS National Research Service Award. Her research is currently funded by NIH. Along with past NIEHS funding she has received several intramural grants as well as the Colgate-Palmolive Grant for Alternative Research from the Society of Toxicology (SOT). Her overall research goal is to elucidate, at the cellular and molecular level, the human health implications of altered antibody expression by xenobiotics such as the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and the role of specific genetic factors in influencing individual susceptibility to xenobiotics. Dr. Sulentic has been very active in training undergraduate and graduate students and is involved in professional societies including the American Society for Pharmacology and Experimental Therapeutics, the American Association of Immunologist, and particularly SOT and the Ohio Valley Regional Chapter.
B.S. (1992), Lake Superior State University, Sault Ste. Marie, Mich.
Ph.D. (1999), Michigan State University, Lansing, Mich.
Postdoctoral (1999-2003), Michigan State University, Lansing, Mich.
Antibodies are an essential component to maintaining health and immunity against a broad spectrum of pathogens. However, environmental stressors can inhibit antibody production resulting in increased susceptibility to infetion. The primary focus of my laboratory is to investigate the role of specific genetic and environmental factors in AhR-mediated regulation of antibody production with implications for the genotypic susceptibility of humans to environmental stressors.
B cells are an important effector cell in maintaining immunity against a wide variety of pathogens. B cells produce and secrete antibodies which have the ability to recognize specific antigens (i.e., foreign molecules) and lead to the clearance of these antigens from the body. B cells and antibodies therefore play an important role in host protection. Exposure to exogenous chemicals either through the diet, pharmaceuticals or environment may impair immune function. In animal models, TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin or dioxin) has been identified as a potent suppressor of B cell function by markedly inhibiting antibody secretion. This is of human relevance and toxicological interest since TCDD is only one representative of a large class of environmental chemicals. The toxic effects of these chemicals may be mediated through the aryl hydrocarbon receptor (AhR) signaling pathway.
The AhR is a cytosolic protein which has affinity for TCDD and like compounds. Binding of TCDD to the AhR results in nuclear translocation of the ligand-receptor complex where it forms a heterodimer with the AhR nuclear translocator (ARNT). The AhR-ARNT complex is a transcription factor that binds to the DNA at dioxin responsive elements within regulatory regions of sensitive genes and regulates transcription. In addition to directly activating the AhR signaling pathway, TCDD has also been shown to modulate the activity of other signaling pathways including the NF-κB/Rel pathway. The specific interactions between the AhR and other signaling pathways are unclear and may be important in the effects of TCDD on B cell function, specifically the inhibition of immunoglobulin (Ig) expression and antibody secretion (secreted form of Ig).
We have found that a regulatory region 3' of the mouse Ig heavy chain gene (Igh) is a sensitive target of a diverse range of environmental stressors, including AhR ligands from the environment (TCDD) and diet. The 3'Igh regulatory region has been purported to regulate Igh expression and isotype class switching. However, these studies have been primarily conducted using mouse models. The human IGH gene and 3'IGH regulatory region is distinct from the mouse and unique, due not only to gene duplication, but also because it is polymorphic with certain alleles associated with a number of autoimmune diseases and hypersensitivity disorders. The effect of AhR ligands and AhR activation on human antibody production, IGH expression, and 3'IGHRR activity is largely unknown.
My laboratory is focused on utilizing human cellular models to test the hypothesis that unique polymorphisms in the 3'IGHRR determine the level of antibody production by human B-lymphocytes in response to environmental stressors that are mediated via the AhR. We utilize several molecular and cellular biology techniques including cell culture of cell lines and primary cells, CRISPR-Cas9 gene editing, MinION nanopore sequencing and bioinformatics, real-time PCR, Western blotting, EMSA analysis, in vitro DNA transfection of mammalian cells, ELISA analysis, and flow cytometry.
The 3'IgH RR has been associated with the occurrence and severity of specific human autoimmune diseases. Chemical-induced alteration in the regulation of the 3'IgH RR may be significant in discovering the presently elusive etiology of some autoimmune diseases. Clearly, understanding how chemicals modify the 3'IgH RR and IgH expression will lead to a better understanding of the basic physiology of IgH expression and will ultimately lead to improved drug development and prediction of potential toxic interactions.
Since environmental stressors and disease states could alter any number of signaling pathways, defining the regulatory processes of antibody production is essential to predicting susceptibility to different environmental stressors and diseases.
Snyder, A.D., Ochs, S.D., Johnson, B.E., Sulentic, C.E.W. Aryl hydrocarbon receptor-induced activation of the human IGH hs1.2 enhancer: Mutational analysis of putative regulatory binding motifs. Molecular Immunology, 2020; 120:164-178.
Ellis, D., Maurer-Gardner, E., Sulentic, C.E.W., Hussain, S. Silver nanoparticle antibacterial efficacy and resistance development in key bacterial species. Biomedical Physics & Engineering Express, 2019; 5(1): 015013. DOI: https://doi.org/10.1088/2057-1976/aad5a7
Liu, J., Law, R. A., Koles, P. G., Saxe, J. C., Bottomley, M., Sulentic, C.E.W. Allelic frequencies of the hs1.2 enhancer within the immunoglobulin heavy chain region in Dayton, Ohio patients screened for celiac disease with duodenal biopsy. Digestive and Liver Disease, Digestive Liver Diseases, 2017; 49:887-892.
Gibson, J. N., Beesetty, P., Sulentic, C. E. W., Kozak, J. A..: Rapid quantification of mitogen-induced blastogenesis in T lymphocytes for identifying immunomodulatory drugs. JoVE, 2016; 118:e55212. http://www.jove.com/video/55212.
Grabinski, C., Sharma, M., Maurer, E., Sulentic, C. E. W., Sankaran, M., Hussain, S.: The effect of shear flow on nanoparticle agglomeration and deposition in in vitro dynamic flow models. Nanotoxicology, 2016; 10:74-83.
Salisbury, R and Sulentic, C. E. W.: The AhR and NF-κB/Rel proteins mediate the inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the 3′ immunoglobulin heavy chain regulatory region. Toxicological Sciences, 2015; 148:443-59.
Wourms, M. J. and Sulentic, C. E. W.: The aryl hydrocarbon receptor regulates an essential transcriptional element in the immunoglobulin heavy chain gene. Cellular Immunology, 2015: 295:60-6.
Sharma, M., Salisbury, R., Hussain, S., Sulentic, C. E. W.: Gold nanoparticles induce transcriptional activity of NF-κB in a B-lymphocyte cell line. Nanoscale, 5:3747 (2013).
Barchowsky, A., Buckley, L. A., Carlson, G. P., Fitsanakis, V. A., Ford, S. M., Genter, M., Germolec, D. R., Leavens, T. L., Lehman-McKeeman, L. D., Safe, S. H., Sulentic, C. E. W., Eidemiller, B. J.: The Toxicology Education Summit: building the future of toxicology through education, Toxicological Sciences, 127:331-338 (2012).
Ochs, S., Liu, J., Fernando, T., Fecher, R., Sulentic, C. E. W.: A dioxin response element in the multiple cloning site of the pGL3 luciferase reporter influences transcriptional activity, Toxicology in Vitro, 26:979-984 (2012).
Fernando, T., Ochs, S., Liu, J., Chambers-Turner, R., Sulentic, C. E. W.: 2,3,7,8-Tetracholorodibenzo-p-dioxin Induces Transcriptional Activity of the Human Polymorphic hs1,2 Enhancer of the 3’Igh Regulatory Region, Journal of Immunology, 188:3294-3306 (2012).
Romer, E.J., Sulentic, C.E.W.: Hydrogen peroxide modulates immunoglobulin expression by targeting the 3’Igh regulatory region through an NFκB-dependent mechanism. Free Radical Research, 45:796-809 (2011).
Henseler, R.A., Romer, E.J., Sulentic, C.E.W.: Chemical-induced Modulation of the 3'IgH regulatory region in the CH12.LX Cell Line: an in vitro Model for Identifying Immunotoxicants that Target B Cell Function. Toxicology, 261:9-18 (2009).
Xiang Z., Schweitzer, B.L., Romer, E.J., Sulentic, C. E. W., DeKoter, R.P.: Ectopic Expression of Spi-C Impairs B Cell Development and Function. European Journal of Immunology, 38:2587-2599 (2008).
Sulentic, C.E.W., Wei, Z., Na, Y.J., Kaminski, N.E.: 2,3,7,8-Tetrachlorodibenzo-p-dioxin, an Exogenous Modulator of the 3'α Immunoglobulin Heavy Chain Enhancer in the CH12.LX Mouse Cell Line. J. Pharm. Exp. Ther. 309:71-78 (2004).
Sulentic, C. E. W., Kang, J.S., Na, Y.J., Kaminski, N.E.: Regulation of the 3'α-hs4 Domain by DRE and κB Binding Proteins. Toxicology. 200:235-246 (2004).
Crawford, R. B., Sulentic, C. E. W., Yoo, B.S., Kaminski, N.E.: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the regulation and posttranslational modification of p27kip1 in lipopolysaccharide-activated B cells. Toxicol. Sciences, 75:333-342 (2003).
Kaminski, N. E., Sulentic, C.E.W., Kang, J.S.: Looking inside the cell for mechanisms of Immunotoxicity: Experimental Design & Approaches Aimed Toward Elucidation of TCDD-mediated B cell Dysfunction. J. Toxicol. Public Health 17:205-210 (2000).
Sulentic, C.E.W., Holsapple, M.P., Kaminski, N.E.: Putative link between Transcriptional Regulation of IgM Expression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin and the Aryl Hydrocarbon Receptor/dioxin-responsive Enhancer Signaling Pathway. J. Pharm. Exp. Ther., 295:705-716 (2000). [Abstract]
Sulentic, C.E.W., Holsapple, M.P., Kaminski, N.E.: AhR-dependent Suppression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin of IgM Secretion in Activated B cells. Mol. Pharm., 53:623-629 (1998).
Williams, C.E., Crawford, R.B., Holsapple, M.P., Kaminski, N.E.: Identification of Functional Aryl Hydrocarbon Receptor and Aryl Hydrocarbon Receptor Nuclear Translocator in Murine Splenocytes. Biochem. Pharmacol. 52:771-780 (1996). [Abstract]
Peer-reviewed Review Publications
Sulentic, C. E. W. and Kaminski, N. E.: The Long Winding Road toward Understanding the Molecular Mechanisms for B-Cell Suppression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Toxicological Sciences, 120:S171-S191 (2011). Solicited for the 50th Anniversary of the Society of Toxicology.
Sulentic, C. E.W., Snyder, A. D., Salisbury, R. L.: Chapter 11.11: The Aryl Hydrocarbon Receptor and Immunity. In: Comprehensive Toxicology (ed. C. McQueen) 3rd edition, Elsevier, Netherlands (in press).
Kaplan, B. L. F., Sulentic, C. E. W., Haggerty, H. G., Holsapple, M. P., Kaminski, N. E.: Chapter 12: Toxic Responses of the Immune System. In: Casarett & Doull’s Toxicology, The Basic Science of Poisons (ed. C. D. Klaassen) 9th edition, McGraw-Hill, USA (in press).
Kaplan, B. L. F., Sulentic, C. E. W., Holsapple, M. P., Kaminski, N. E.: Chapter 12: Toxic Responses of the Immune System. In: Casarett & Doull’s Toxicology, The Basic Science of Poisons (ed. C. D. Klaassen) 8th edition, McGraw-Hill, USA (2013).
Solicited, Non-peer-reviewed Publications
Sulentic, C.E.W.: Modulation of Immunoglobulin Gene Expression. In: Current Protocols in Toxicology Unit 18.13, John Wiley & Sons, Inc., Hoboken, N.J. (2008).
Sulentic, C.E.W. and Kaminski, N.E.: Humoral Immunity. In: Encyclopedic Reference of Immunotoxicology (ed. H.-W. Vohr) XXII, 730, Springer Press Heidelberg, Germany (2005).
Kaminski, N.E. and Sulentic, C.E.W.: B cell. In: Encyclopedic Reference of Immunotoxicology (ed. H.-W. Vohr) XXII, 730, Springer Press Heidelberg, Germany (2005).
American Association of Immunologists (AAI)
American Chemical Society (ACS)
American Society for Pharmacology and Experimental Therapeutics (ASPET)
National ASPET Toxicology Division
National Organization for Women
National Science Teaching Association
Society for College Science Teachers
National Society of Toxicology (SOT)
Women in Toxicology
In Vitro and Alternative Methods
Ohio Valley SOT Regional Chapter
Sigma Xi, the Scientific Research Society
Textbook and Academic Authors Association
Elected to the Presidential chain for the Women in Toxicology Special Interest Group, Society of Toxicology, 2019 -2023
Elected to the Society of Toxicology Council as a Councilor, 2018-2021
Faculty Grant, Women in Science Giving Circle, Wright State University, 2016
Distinguished Service Award, Ohio Valley Society of Toxicology, 2015
Research paper “The AhR and NF-κB/Rel proteins mediate the inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the 3′ immunoglobulin heavy chain regulatory region” selected for the Editor’s Highlights in the Journal Toxicological Sciences, 2015
Research highlighted in "Next Generation of Immunotoxicologists", Japan Society of Toxicology, 2011
Leadership Academy, Boonshoft School of Medicine, 2010
Elected to the Presidential chain for the Ohio Valley Society of Toxicology Regional Chapter, 2009-2013
Elected Secretary/Treasurer of the National American Society fro Pharmacology and Experimental Therapeutics (ASPET) Toxicology Division, 2009-2012
Elected Secretary of the Ohio Valley Society of Toxicology, Regional Chapter, 2006-2009
Excellence in Medical Education and Research Award, Wright State University Academy of Medicine, 2008
Colgate Palmolive Grant for Alternative Methods, Society of Toxicology, 2006
AAI Junior Faculty Travel Award, American Association of Immunologists, 2006
National Research Service Award, NIEHS, 2000