Dr. Aleksunes is Professor in the Rutgers University, Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, Project Lead of the NJ Alliance for Clinical and Translational Science CTSA Workforce Development Core, and Director of the Joint Graduate Program in Toxicology and the Summer Undergraduate Research Fellowship. Dr. Aleksunes is also a member of the CounterAct Research Center of Excellence where she Co-Leads the Research Education Core and Pharmacology and Drug Development Core. Within the NIEHS P30 Center for Environmental Exposures and Disease, Dr. Aleksunes is Co-Director of the Environmental/Chemical Pathology Core and Co-Director of Career Development and Mentoring.
Drugs and chemicals are often too large to enter and exit cells unassisted. Transporter proteins can be used as gates that regulate which chemicals leave cells. In fact, the ATP-binding cassette transporters (ABC) are members of a superfamily of transporters found in the plasma membrane. ABC transporters function as efflux pumps that remove chemicals from the cell. Our laboratory studies members of three families of efflux transporters: ABCB1 (Multidrug resistance protein 1, MDR1, P-glycoprotein), ABCC1-6 (Multidrug resistance-associated proteins, MRP), and ABCG2 (Breast cancer resistance protein, BCRP). These transporters are important in removing chemicals from the liver and kidneys and can protect against target organ toxicity. Similarly, these efflux pumps are expressed in the placenta and participate in maternal-fetal xenobiotic disposition, thereby protecting the developing fetus from toxicant exposure.
Dr. Aleksunes’ laboratory investigates how drug transporters in the liver, kidneys, brain, and placenta protect against the accumulation and toxicity of pharmaceuticals and environmental chemicals. Her studies aim to 1) characterize substrates and inhibitors for efflux transporters, 2) determine how genetic variants influence transporter function, and 3) understand the regulatory mechanisms that control expression of transporters. Dr. Aleksunes’ laboratory utilizes molecular biology, cell biology, in vivo transgenic animal, explant human tissue, biomarkers of toxicity, and pharmacokinetic approaches to study the interplay of drug transport and toxicology.
Dr. Aleksunes and her laboratory are funded by NIH R01ES021800, R01ES029275, R01GM123330, and F31ES029794 Dr. Aleksunes is Principal Investigator for T32ES007148 and R25ES020721 and Intern Programs from the Society of Toxicology and the American Society for Pharmacology and Experimental Therapeutics. She also participates in U54TR002258 and U54AR055073.
The Aleksunes laboratory includes research scientists (Xia Wen), graduate students (Ludwik Gorczyca, Danielle Kozlosky, and Maxine Abustan), postdoctoral fellows (Ranran Zhang and Lauren Walker), and undergraduate students (Fatimah Mosaad, Brian Rinelli, Chris Pella, Duaa Eisa, Hye Min Shin, Perihan Badawy, Rebecca Sun, and Victoria Woo). Students from China Pharmaceutical University and Sun Yat-Sen University spend rotations in the Aleksunes laboratory as well.
Highlights from the research team include:
- Identification of pharmacogenetic risk factors, drug interactions, and biomarkers for cisplatin-induced nephrotoxicity in humans.
- Investigation of enterohepatic bile acid signaling and homeostasis during pregnancy.
- Characterization of environmental chemicals as substrates and inhibitors of human placental efflux transporters.
- Elucidation of regulatory mechanisms controlling transporter expression in the placenta.
- Characterization of cell-cell communication between microglia and brain endothelial cells.
- Identification of transporters in the blood-brain barrier that regulate exposure to pesticides.
- Screening of diverse chemical sets to inform the development and refinement of virtual Adverse Outcome Pathways (vAOPs).
In the News
- Zhang, R, Walker, L, Wen, X, Doherty, C, Gorczyca, L, Buckley, B, Barrett, ES, Aleksunes, LM. Placental BCRP transporter reduces cadmium accumulation and toxicity in immortalized human trophoblasts. Reprod Toxicol. 2023;121 :108466. doi: 10.1016/j.reprotox.2023.108466. PubMed PMID:37660740
- Russo, DP, Aleksunes, LM, Goyak, K, Qian, H, Zhu, H. Integrating Concentration-Dependent Toxicity Data and Toxicokinetics To Inform Hepatotoxicity Response Pathways. Environ Sci Technol. 2023;57 (33):12291-12301. doi: 10.1021/acs.est.3c02792. PubMed PMID:37566783 PubMed Central PMC10448720
- Rivera-Núñez, Z, Hansel, M, Capurro, C, Kozlosky, D, Wang, C, Doherty, CL, Buckley, B, Ohman-Strickland, P, Miller, RK, O’Connor, TG et al.. Prenatal Cadmium Exposure and Maternal Sex Steroid Hormone Concentrations across Pregnancy. Toxics. 2023;11 (7):. doi: 10.3390/toxics11070589. PubMed PMID:37505555 PubMed Central PMC10384739
- Kozlosky, D, Lu, A, Doherty, C, Buckley, B, Goedken, MJ, Miller, RK, Barrett, ES, Aleksunes, LM. Cadmium reduces growth of male fetuses by impairing development of the placental vasculature and reducing expression of nutrient transporters. Toxicol Appl Pharmacol. 2023;475 :116636. doi: 10.1016/j.taap.2023.116636. PubMed PMID:37487938 PubMed Central PMC10528997
- Lazofsky, A, Brinker, A, Gupta, R, Barrett, E, Aleksunes, LM, Rivera-Núñez, Z, Buckley, B. Optimized extraction and analysis methods using liquid chromatography-tandem mass spectrometry for zearalenone and metabolites in human placental tissue. Heliyon. 2023;9 (6):e16940. doi: 10.1016/j.heliyon.2023.e16940. PubMed PMID:37484340 PubMed Central PMC10361036
- Mosquera, AM, Aleksunes, LM. Engaging Students in Pharmacogenetics: Patient Case Studies Using the PharmGKB Website. CourseSource. 2023;10 :. doi: 10.24918/cs.2023.10. PubMed PMID:37476533 PubMed Central PMC10357923
- Coyte, RM, Darrah, T, Olesik, J, Barrett, E, O’Connor, TG, Brunner, J, Love, T, Perez-D’Gregorio, R, Wang, HZ, Aleksunes, LM et al.. Gadolinium during human pregnancy following administration of gadolinium chelate before pregnancy. Birth Defects Res. 2023;115 (14):1264-1273. doi: 10.1002/bdr2.2209. PubMed PMID:37334869
- Chung, E, Russo, DP, Ciallella, HL, Wang, YT, Wu, M, Aleksunes, LM, Zhu, H. Data-Driven Quantitative Structure-Activity Relationship Modeling for Human Carcinogenicity by Chronic Oral Exposure. Environ Sci Technol. 2023;57 (16):6573-6588. doi: 10.1021/acs.est.3c00648. PubMed PMID:37040559 PubMed Central PMC10134506
- Barrett, ES, Rivera-Núñez, Z, Getz, K, Ohman-Strickland, P, Zhang, R, Kozlosky, D, Doherty, CL, Buckley, BT, Brunner, J, Miller, RK et al.. Protective role of the placental efflux transporter BCRP/ABCG2 in the relationship between prenatal cadmium exposure, placenta weight, and size at birth. Environ Res. 2023;225 :115597. doi: 10.1016/j.envres.2023.115597. PubMed PMID:36863650 PubMed Central PMC10091184
- Meakin, C, Kim, C, Lampert, T, Aleksunes, LM. High-throughput screening of toxicants that modulate extravillous trophoblast migration. Toxicol Lett. 2023;375 :1-7. doi: 10.1016/j.toxlet.2022.12.004. PubMed PMID:36535517 PubMed Central PMC9877196