Silviya Zustiak, Ph.D.

Assistant Professor


Education

Ph.D. in Chemical and Biochemical Engineering, University of Maryland Baltimore County (UMBC)
B.S./M.S. in Bioelectrical Engineering, Technical University, Sofia, Bulgaria

Research Interests

Zustiak’s primary research interests are in hydrogel biomaterials and tissue engineering, with emphasis on developing novel biomaterials as cell scaffolds and drug screening platforms, and elucidating matrix structure-property relationships as well as cell-matrix interactions. Biomaterial-based models are crucial for bridging the gap between traditional tissue culture and animal models by providing a cell environment that closely mimics real tissue. This research is highly multidisciplinary, merging the fields of engineering, materials science, and biology.

Research Projects
Decoupling key cell-matrix interactions that affect cancer cell responsiveness to anticancer drugs in bioengineered 2D extracellular matrix. The overall goal of this project is to gain a fundamental grasp of key cell-matrix interactions that affect the cells’ responsiveness to anticancer drugs, with emphasis on matrix stiffness, integrin adhesions and their synergistic effects, since these parameters profoundly affect cancer cell fate including the onset of malignancy. The underlying hypothesis for this work is that matrix stiffness and integrin presentation are also important in drug resistance mechanisms (e.g. by altering cytoskeletal tension or integrin expression).

Zustiak is also studying the role of matrix stiffness on cancer cell responsiveness to anticancer drugs. For this project, she is performing methodical and quantitative analysis of the impact of substrate stiffness on anticancer drug cytotoxicity. She uses polyacrylamide (PA) gels that span a range of stiffness (0.3 to 300 kPa), coated with extracellular matrix (ECM) proteins to promote cell attachment. High-throughput assays are being developed. Gel stiffness is measured by rheometry and by atomic force microscopy (AFM). Various cancer cell types are subjected to treatment with different concentrations of anticancer drugs for a pre-determined amount of time. She then quantitatively measures cell fate including cell viability, proliferation, morphology, apoptosis, signaling, cell cycle as well as drug IC50.

Another project Zustiak is working on is the role of integrin adhesions on cancer cell responsiveness to anticancer drugs. The aim of this project is to isolate the effect of integrin presentation (by precisely controlling the concentration and type of integrin binding sites) from other matrix properties (such as stiffness) and assess its impact on the responsiveness of cancer cells to anticancer drugs. In this project, she uses methods, drugs, and cell types similar to those indicated above, and we quantify similar outputs. In addition, she explores the synergistic effects of ligand density and substrate stiffness.

Zustiak is researching the role of 3D environment in the evaluation of anticancer drug sensitivity. Despite overwhelming evidence on the impact of the microenvironment on tumorogenesis and drug resistance, over 85% of tumor research is still conducted on 2D plastic, mainly due to lack of suitable biomaterial-based alternatives. This project utilizes biomaterial scaffolds for elucidating cell-matrix interactions as related to drug toxicity in 3D environments. She methodically investigates cell responses such as viability, proliferation, apoptosis, cell cycle, and cell signaling to various microenvironmental conditions such as matrix stiffness, porosity, and adhesion sites. Specific mechanisms responsible for drug sensitivity in 3D versus 2D environments are investigated.

Labs and Facilities

Soft Tissue Engineering Laboratory

Publications and Media Placements

Printed Archival Peer-Reviewed Journals
Zustiak, S.P., Nossal, R., Sackett, D., “Multiwell stiffness assay for the study of cell responsiveness to cytotoxic drugs”, Biotechnology & Bioengineering, 2013, doi: 10.1002/bit.25097

Zustiak, S.P., Pubill, S., Ribeiro, A., Leach, JB., “Hydrolytically degradable poly(ethylene glycol) hydrogel scaffolds as a cell delivery vehicle: characterization of PC12 cell response”, Biotechnology Progress, 2013, 29(5), 1255-1264 doi: 10.1021/btpr.1761

Zustiak, S.P., Riley, J., Boukari, H., Gandjbakhche, H.A., Nossal, R., “Effects of Multiple Scattering on Fluorescence Correlation Spectroscopy Measurements of Particles Moving within Optically Dense Media”, Journal of Biomedical Optics, 2012, 17(12), 125004-125004. doi: 10.1117/1.JBO.17.12.125004

Zustiak, S.P., Wei, Y., Leach, J.B., “Protein-hydrogel interactions in tissue engineering: mechanisms and applications”, Tissue Engineering Reviews, 2012, 19(2): 160-171. doi: 10.1089/ten.teb.2012.0458

Zustiak, S.P., Nossal, R., Sackett, D., “Hindered Diffusion in Polymeric Solutions Studied by Fluorescence Correlation Spectroscopy”, Biophysical Journal, 2011, 101, 255-264. doi: 10.1016/j.bpj.2011.05.035

Zustiak, S.P., Leach, J.B., “Characterization of Protein Release from Hydrolytically Degradable Poly(ethylene glycol) Hydrogels”, Biotechnology & Bioengineering, 2011, 108, 197-206. doi: 10.1002/bit.22911

Zustiak, S.P., Leach, J.B., “Hydrolytically Degradable Poly(ethylene glycol) Hydrogel Scaffolds with Tunable Degradation and Mechanical Properties”, Biomacromolecules, 2010, 11, 1348-1357. doi: 10.1021/bm100137q

Zustiak, S.P., Boukari, H., Leach, J.B., “Solute Diffusion and Interactions in Cross-linked Poly(ethylene glycol) Hydrogels Studied by Fluorescence Correlation Spectroscopy”, Soft Matter, 2010, 6, 3609-3618. doi: 10.1039/C0SM00111B

Zustiak, S.P., Durbal, R., Leach, J.B., “Influence of Cell-adhesive Peptide Ligands on Poly(ethylene glycol) Hydrogel Physical, Mechanical and Transport Properties”, Acta Biomaterialia, 2010, 6, 3404-3414. doi: 10.1016/j.actbio.2010.03.040

Petrova, S., Kostov, Y., Jeffris, K., Rao, G., “Optical Ratiometric Sensor for Alcohol Measurements”, Analytical Letters, 2007, 40(3), 715-727. doi: 10.1080/00032710601017847

Pandelova, A., Petrova, S., Neykov, A., “Experimental Research of a Hybrid Biosensor for Ecological Purposes”, Biotechnology & Biotechnological Equipment, 2003, 17(1), 187-193.

Conference Abstracts
Zustiak, S.P., “Substrate stiffness affects cancer cell responsiveness to cytotoxic drugs”, (Oral), American Institute of Chemical Engineers (AIChE) Annual Meeting, San Francisco, CA, November, 2013.

Zustiak, S.P., Nossal, R., Sackett, D., “High-throughput stiffness assay for the study of cancer cell susceptibility to anti-cancer drugs”, (Oral), American Institute of Chemical Engineers (AIChE) Annual Meeting, Pittsburg, PA, October 2012.

Zustiak, S.P., Nossal, R., Sackett, D., “A Fluorescence Correlation Spectroscopy Study of Hindered Probe Diffusion in Complex Media”, (Oral), American Institute of Chemical Engineers (AIChE) Annual Meeting, Minneapolis, MN, October 2011.

In Proceedings
Zustiak, S.P., Ferguson, D., Nossal, R., Sackett, D., “High-throughput stiffness assay for the study of cancer cell susceptibility to anti-cancer drugs”, AIChE Symposia Proceedings, 2012 Annual Fall Meeting, Pittsburg, PA, October 2012.

Petrova, S., Leach, J.B., “Development of a novel hydrolytically degradable PEG hydrogel with tunable degradability and protein release”, MRS Symposia Proceedings, 2008 Annual Fall Meeting, Boston, MA, December 2008.

Conference Posters
Zustiak, S.P., Kalinowski, K., Ahmed, N., Cole, C., “Effect of stiffness and dimensionality on cancer cell responsiveness to cytotoxic drugs”, (Poster), Functional Analysis and Screening Technologies, Boston, MA, October 2013. (Best Poster Award)

Zustiak, S.P., Kalinowski, K., Ahmed, N., Cole, C., “Substrate stiffness affects cancer cell responsiveness to cytotoxic drugs”, (Poster), Gordon Research Conference: Biomaterials & Tissue Engineering, Holderness, NH, July 2013

Kalinowski, K., Zustiak, S.P., “The role of dimensionality on cancer cell response to cytotoxic drugs”, (Poster), Biomedical Engineering Society (BMES)Annual Meeting, Seattle, WA, September 2013

Ferguson, D., Zustiak, S.P., Nossal, R., Sackett, D., “Development of a Polyacrylamide-Based Stiffness Assay for “High-Throughput” Drug Testing”, (Poster), Annual Biomedical Research Conference for Minority Students (ABRCMS), San Jose, CA, November 2012.

Ferguson, D., Zustiak, S.P., Nossal, R., Sackett, D., “Development of a Polyacrylamide-Based Stiffness Assay for “High-Throughput” Drug Testing”, (Poster), National Institute of Health (NIH) Summer Research Program Poster Day, Bethesda, MD, August 2012.

Zustiak, S.P., Nossal, R., “Effects of Scattering on Fluorescence Correlation Spectroscopy Measurements of Diffusion in Complex Media”, (Poster), Predictive Functional Tissue Models, Boston, MA, November, 2011.

Zustiak, S.P., Nossal, R., Sackett, D., “Hindered Diffusion in Polymeric Solutions Studied by Fluorescence Correlation Spectroscopy”, (Poster), Biophysical Society Annual Meeting, Baltimore, MD, March 2011.

Taylor, T., Zustiak, S.P., Nossal, R., Sackett, D., “Development of Poly(ethylene Glycol)-Collagen 3D Scaffolds”, (Poster), 14th Annual Undergraduate Research Symposium in the Chemical and Biological Sciences at UMBC, Baltimore, MD, October 2011.

Taylor, J., Nossal, R., Sackett, D., Zustiak, S.P., “Development of Poly(ethylene Glycol)-Collagen 3D Scaffolds”, (Poster), National Institute of Health (NIH) Summer Research Program Poster Day, Bethesda, MD, August 2011.

Patents
Kostov, Y, Petrova, S., Rao, G., “Optical Alcohol Sensor”, Provisional Application 60/720, 444. UMBC Ref. No. 2482YK, September 2005. Books * Zustiak, S.P., “Hydrolytically degradable polyethylene glycol (PEG) hydrogel: synthesis, gel formation, and characterization”, INVITED book chapter, for Neuromethods: Extracellular Matrix, Humana Press, accepted. doi: 10.1002/bit.22911 * Feature Article in Tissue Engineering Part B: Reviews April 2013 Issue.

Community Work

Silviya Petrova Zustiak, Ph.D. joined the Biomedical Engineering Department as an assistant professor in spring 2013. During her doctoral studies, under the guidance of Jennie Leach, Silviya developed hydrogels as scaffolds for neural tissue engineering. Zustiak conducted post-doctoral research for three years at the National Institutes of Health in Bethesda, MD, at the Laboratory of Integrative and Medical Biophysics under Ralph Nossal, utilizing spectroscopic techniques to study solute transport within hydrogel matrices.