Olivia Merkel, Ph.D.
Department of Pharmaceutical Sciences
Eugene Applebaum College of Pharmacy and Health Sciences
259 Mack Avenue, Room 3132
Detroit, MI 48201-2417
tumor targeting (transferrin and folate receptor targeting)
synthesis and bioengineering of nanocarriers
whole body imaging
The Merkel lab is interested in smart siRNA delivery systems. RNA interference (RNAi) is a Nobel-Prize-winning technology which has been used as a lab tool in the last decade for functional genomics. It has recently attracted strong interest to evaluate its therapeutic potential; however, delivery of siRNA is so far the greatest hurdle. Therefore, we develop synthetic and genetically engineered nano-sized delivery systems for siRNA and optimize their in vitro characteristics such as reproducibility of formulation, size, siRNA protection and release, toxicity, immunogenicity and bioactivity.
Due to rapid degradation by nucleases and fast excretion upon systemic injection, local administration of siRNA offers more clinical relevance. By local administration, both the dose and systemic side effects can be decreased. We are mostly interested in pulmonary administration for local effects and nasal administration for subsequent delivery to the brain via the olfactory bulb.
To reach specific cell populations within the lung, to reach ovarian cancer cells or glioblastoma, or to deliver siRNA into the brain, we attach targeting ligands to the surface of the delivery systems. These targeting moieties have a strong affinity with the target cells and tissues. Due to this high affinity, these delivery systems are also investigated for their ability to serve as diagnostic tool after radiolabeling. A theragnostic nanomedicine delivers siRNA to the target cells but also detects circulating or distant target cells, e.g. circulating tumor cells or metastases.
Our goal is to develop novel siRNA-based nanomedicines for therapy of a range of diseases. We mainly focus on the treatment of lung cancer, glioblastoma and ovarian cancer.
Xie Y, Killinger B, Moszczynska A, Merkel OM. Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine. Molecules. 2016;21:E1334.
Jones SK, Merkel OM. Tackling breast cancer chemoresistance with nano-formulated siRNA. Gene Ther. 2016;23:821-8.
Mohammadi M, Li Y, Abebe DG, Xie Y, Kandil R, Kraus T, Gomez-Lopez N, Fujiwara T, Merkel OM. Folate receptor targeted three-layered micelles and hydrogels for gene delivery to activated macrophages. J Control Release. 2016;244:269-79.
Abebe DG, Kandil R, Kraus T, Elsayed M, Fujiwara T, Merkel OM. Biodegradable Three-Layered Micelles and Injectable Hydrogels. Methods Mol Biol. 2016;1445:175-85.
Movassaghian S, Xie Y, Hildebrandt C, Rosati R, Li Y, Kim NH, Conti DS, da Rocha SR, Yang ZQ, Merkel OM. Post-Transcriptional Regulation of the GASC1 Oncogene with Active Tumor-Targeted siRNA-Nanoparticles. Mol Pharm. 2016;13:2605-21.
Zhong Q, Merkel OM, Reineke JJ, da Rocha SR. Effect of the Route of Administration and PEGylation of Poly(amidoamine) Dendrimers on Their Systemic and Lung Cellular Biodistribution. Mol Pharm. 2016;13:1866-78.
Xie Y, Kim NH, Nadithe V, Schalk D, Thakur A, Kılıç A, Lum LG, Bassett DJ, Merkel OM. Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma. J Control Release. 2016;229:120-9.
Liu L, Zheng M, Librizzi D, Renette T, Merkel OM, Kissel T. Efficient and Tumor Targeted siRNA Delivery by Polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol)-folate (PEI-PCL-PEG-Fol). Mol Pharm. 2016;13:134-43.
Jones SK, Lizzio V, Merkel OM. Folate Receptor Targeted Delivery of siRNA and Paclitaxel to Ovarian Cancer Cells via Folate Conjugated Triblock Copolymer to Overcome TLR4 Driven Chemotherapy Resistance. Biomacromolecules. 2016;17:76-87.
Jones S, Merkel O. Indium-Labeling of siRNA for Small Animal SPECT Imaging.
Methods Mol Biol. 2016;1372:79-88.
Feldmann DP, Merkel OM. The advantages of pulmonary delivery of therapeutic siRNA. Ther Deliv. 2015;6:407-9.
Merkel OM, Kissel T. Quo vadis polyplex? J Control Release. 2014;190:415-23.
Merkel OM, Rubinstein I, Kissel T. siRNA Delivery to the lung: What's new? Adv Drug Deliv Rev. 2014;75C:112-128.
Endres T, Zheng M, Kılıç A, Turowska A, Beck-Broichsitter M, Renz H, Merkel OM, Kissel T. Amphiphilic biodegradable PEG-PCL-PEI triblock copolymers for FRET-capable in vitro and in vivo delivery of siRNA and quantum dots. Mol Pharm. 2014;11:1273-81.
Elsayed M, Merkel OM. Nanoimprinting of topographical and 3D cell culture scaffolds. Nanomedicine (Lond). 2014;9:349-66.
Elsayed M, Corrand V, Kolhatkar V, Xie Y, Kim NH, Kolhatkar R, Merkel OM. Influence of oligospermines architecture on their suitability for siRNA delivery. Biomacromolecules. 2014;15:1299-310.
Turowska A, Librizzi D, Baumgartl N, Kuhlmann J, Dicke T, Merkel O, Homburg U, Höffken H, Renz H, Garn H. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs. Toxicol Appl Pharmacol. 2013;272:365-72.
Merkel OM, Marsh LM, Garn H, Kissel T. Flow cytometry-based cell type-specific assessment of target regulation by pulmonary siRNA delivery. Methods Mol Biol. 2013;948:263-73.
Education and Training:
PhD 2009, Philipps-Universität Marburg, Germany
MS 2006, Martin-Luther-Universität Halle-Wittenberg, Germany
PharmD 2005, Philipps-Universität Marburg, Germany