The main focus of our toxicology-related research is in the development of reactive oxygen species (ROS)-producing nanostructures as cancer therapeutics. We develop many types of metal oxide nanoparticles (NPs) such as ZnO and core/shell structures such as ZnO/Au and Fe3O4/ZnO, which are capable of producing ROS by UV or X-ray excitation, leading to cancer cell death.
In addition, we are interested in understanding the mechanisms involved in cancer cell cytotoxicity by these ROS-producing ZnO NPs through the integration of both computational and experimental approaches. Our methodology centers on the modeling of the molecular pathways affected by these perturbations using probabilistic Boolean network formalism. Temporal high throughput gene expression data representing these perturbations is used to identify pathways overrepresented among significantly perturbed genes, focusing on those known to be involved in the central pathways related to cellular death. We focus on the Nrf2/Keap1 pathway, which is the main pathway responsible for cell defense against oxidative stress caused by various perturbations, including ROS-producing nanostructured materials, and maintaining the cellular redox balance at physiological levels, and look for connections between this protective signaling pathway and the regulation of cellular apoptosis, necrosis and autophagy.
Collaborators in this area of research include Surinder P. Singh and Jaime Seguel from UPR-Mayaguez, Braulio Jimenez from UPR-Medical Sciences, Anil Sood from MD Anderson and Ilya Shmulevich from the Systems Biology Institute.
Rodriguez-Martinez C, Joshi P, Vera JL, Ramirez-Vick JE, Perales O, Singh SP. Cytotoxic studies of PEG functionalized ZnO Nanoparticles on MCF-7 cancer cells. BioNanotech Proceedings (2011).
Lluberes M, Seguel J, Ramírez-Vick JE. Markov Model Checking of Probabilistic Boolean Networks Representations of Genes,” International Conference on Bioinformatics & Computational Biology. BioComp Proceedings (2011).
Arya SK, Sahab S, Ramirez-Vick JE, Guptab V, Bhansalia S, Singh SP. Recent Advances in ZnO Nanostructures and Thin Films for Biosensor Applications. Chemical Reviews, Under Review (2011).Joshi P, Chakraborti S, Chakrabarti P, Ansari ZA, Ramirez-Vick JE, Singh SP, Shanker V. Anti-Tumor Chloroquine-Gold Nanocomposites and their Binding Interaction with Bovine Serum Albumin: Biophysical and Biochemical Aspects of Protein Binding,” Colloids and Surfaces B: Biointerfaces, Final Review (2011).
Acevedo-Morantes CY, Acevedo-Morantes MT, Suleiman-Rosado D, Sing SP, Ramírez-Vick JE, “Evaluation of the Cytotoxic Effect of Liposome-Encapsulated Camptothecin on MCF7 Breast Cancer Cells,” In Preparation (2011).
Acevedo-Morantes CY, Meléndez E, Singh SP, Ramírez-Vick JE, “Cytotoxic effect of Ferrocene and Ferrocenium Ions on MCF7 Breast Cancer Cells,” In Preparation (2011).