(6y) Multiscale Biomechanics of Platelet-Driven Blood Clot Contraction and Intracellular Mechanisms of Its Termination

My primary research goals are directed toward understanding the basic mechanisms in biological systems using engineering principles, computational modeling, and biophysics. As a faculty research associate and postdoctoral fellow at the University of Pennsylvania, UC Riverside, Argonne National Lab, and University of Notre Dame, I have balanced experiments and modeling approaches to study transport, mechanical and structural properties of biopolymer networks, biomechanics of blood clot retraction and interaction of cancer cells with the extracellular matrix. I have co-authored over twenty-five peer-reviewed publications, including seventeen first-author papers, with the most recent ones published in Nature Communications, Biomaterials, Haematologica, Oncogene, Acta Biomaterialia, Journal of the Royal Society Interface, Matrix Biology, Soft Matter, Scientific Reports, Biomedical Optics Express, Langmuir.

Successful Proposals: AHA Scientist Development Grant (PI), Walter Cancer Foundation Grant (PI), U01 NIH (Role: Co-I)

Teaching Experience:

As a visiting research assistant professor at the University of Notre Dame in 2012-2014, I had an opportunity to design and lecture my own interdisciplinary course of Topics in Applied Mathematics for graduate students (fall semester 2012). This course introduced graduate students to basic modeling approaches for solving various problems in biomedical engineering such as hemodynamics, tissue optics, drug delivery, characterization of biosensors as well as analysis of experimental data. I have found this an ideal opportunity to merge teaching with my current research interests. I was very pleased to teach the same course in the spring semester 2014.

Furthermore, I successfully taught large undergraduate courses on Applied Linear Algebra (Fall 2014) and Probability and Statistics (Spring 2016) at the Department of Applied and Computational Mathematics and Statistics at Notre Dame. The objective of the first course was to impart the fundamental knowledge of linear algebra and computational linear algebra that is needed to solve matrix algebra problems that arise in various applications. In the Probability course I have taught students concepts in statistics and probability with practical applications to various problems in science.

Future Directions:

Extracellular cues have a profound effect on a wide range of cellular behaviors, including motility, growth, adhesion, differentiation, apoptosis, and signal transduction. The long-term goal of my future research is to develop and use novel interdisciplinary approaches to study the interactions between cells and extracellular matrix in biological systems which importance is evident from its relation to a variety of disorders including but not limited to blood clotting and cancer as well as to the design of novel biomaterials.

One of the short-term goals would be to delineate and quantitatively characterize multiscale biomechanical and structural mechanisms of platelet-induced clot contraction. My projects will study the impact of cellular biomechanical function and metabolic state on the structural and mechanical properties of blood clots and plasma-derived biologically active biomaterials. In another project I will examine the role of biomechanical forces in cancer progression and metastasis.

Selected Publications:

1. Kim O.V., Nevzorova T.A., Mordakhanova E.R., Ponomareva A.A., Andrianova I.A., Le Minh G., Daminova A.G., Peshkova A.D., Alber M.S., Vagin, O., Litvinov R.I., Weisel J.W. (2019). Fatal dysfunction and disintegration of thrombin-stimulated platelets. Haematologica, 104(9),1-13.
2. Kim O.V., Litvinov R.I., Alber M.S., Weisel J.W. (2017) Quantitative structural mechanobiology of platelet-driven blood clot contraction. Nature Communications, 8, 1274.
3. Britton, S., Kim, O., Pancaldi, F., Xu, Z., Litvinov, R.I., Weisel, J.W. and Alber, M., (2019). Contribution of nascent cohesive fiber-fiber interactions to the non-linear elasticity of fibrin networks under tensile load. Acta Biomaterialia, 94, 514 – 523.
4. Klymenko Y.*, Kim O.*, Loughran E., Yang J., Lombard R., Alber M., Stack M.S. (2017) Cadherin composition and multicellular aggregate dynamics in organotypic models of epithelial ovarian cancer intraperitoneal metastasis. Oncogene, 36, 5840–5851
5. Kim O.V., Litvinov RI, Chen J, Chen DZ, Weisel JW, Alber MS. (2017) Compression-induced structural and mechanical changes of fibrin-collagen composites. Matrix Biology, 60, 141-156.
6. Kim O.V., Liang X., Litvinov R.I., Weisel J.W., Alber M.S., Purohit P.K. (2015) Foam-like compression behavior of fibrin networks. Biomechanics and Modeling in Mechanobiology, 1-16.

7. Kim O.V., Litvinov, R. Weisel J., and Alber M.S. (2014) Nonlinear structural mechanics of fibrin networks under compression, Biomaterials, 35, 6739-6749