Ivan
V. Maly
Assistant Professor of Computational Biology
Office: BST3-3090 (
Telephone: 412-648-7771
Email: maly@ccbb.pitt.edu
The general direction of research in my group is theoretical development, computational analysis, and experimental validation of quantitative models that explain cellular morphogenesis from the systems standpoint, integrating molecular motor-driven transport, cytoskeleton dynamics, and cell signaling. We are especially interested in mechanisms of structural polarization of T cells towards infected cells during immune response. The basic mechanism of this process remain largely unknown in spite of the comparatively deep understanding of the molecules involved in it. This suggests to us that the polarization arises from unintuitive quantitative effects of the interaction between different subcellular processes. To uncover these system effects, we develop integrative computer models of T cells and compare them with our multidimensional live-cell microscopy data. Deciphering the cell-level mechanism of T cell polarization is important for building the future higher-level predictive models, because the polarization in these cells underlies on the cellular level the specificity of the immune response. It is central to elimination of infected and cancer cells, induction of immunological memory, and stimulation of antibody production. At the same time, viruses attacking the immune system exploit the T cell polarization for their propagation. Some of the polarization mechanisms appear to be shared between cell types and underlie cellular activities as varied as wound healing and bone remodeling, which is subverted in osteoporosis. Tackling these systems-level polarization mechanisms entails developing the new methodology of quantitative cell biology, whose future applications promise to become as wide as those of the present-day molecular biosciences.
Group
Dr. Sergey N. Arkhipov, Postdoctoral Associate (cell biology and microscopy)
Dr. MunJu Kim, Research Associate (biomechanics and numerical methods)
Mr. Aabid Shariff, PhD student of Computational Biology
Mr. Kris Ghosh, intern
Funding
RO1 grant from National Institutes of General Medical Sciences, of Biological Imaging and Bioengineering, and of Allergy and Infectious Diseases
Interfaces award from Howard Hughes Medical Institute and National Institute of Biological Imaging and Bioengineering
Affiliations
Department of Computational Biology, University of Pittsburgh School of Medicine
Center for Bioimage Informatics at Carnegie Mellon University
Joint CMU-Pitt Ph.D. Program in Computational Biology
Education and training
Diploma, Moscow State University, 1999, with I. A. Vorobjev
Ph.D., Northwestern University, 2002, with G. G. Borisy
Postdoc, Massachusetts Institute of Technology, 2003, with D. A. Lauffenburger
Publications
Most recent
S.N. Arkhipov and I.V. Maly. Quantitative analysis of the role of receptor
recycling in T cell polarization. Biophys. J., online ahead
of print.
S.N. Arkhipov and I.V. Maly. Contribution of whole-cell optimization via cell body rolling to polarization
of T cells. Phys. Biol.,
3:209–219 (2006).
On cell signaling
I.V. Maly, H.S. Wiley, and D.A. Lauffenburger. Self-organization of polarized cell signaling via autocrine circuits: computational model analysis. Biophys. J., 86:10–22 (2004).
D.J. Tschumperlin, G. Dai, I.V. Maly, T. Kikuchi, L.H. Laiho, A.K. McVittie, K.J. Haley, C.M. Lilly, P.T.C. So, D.A. Lauffenburger, R.D. Kamm, and J.M. Drazen. Mechanotransduction via growth factor shedding into a compliant extracellular space. Nature, 429:83–86 (2004).
I.V. Maly, R.T. Lee, and D.A.
Lauffenburger. A
model for mechanotransduction in cardiac muscle:
effects of extracellular matrix deformation on autocrine
signaling. Ann. Biomed.
On actin
dynamics
I.V. Maly and G.G. Borisy. Self-organization of a propulsive actin network as an evolutionary process. Proc. Natl. Acad. Sci. USA, 98:11324–11329 (2001).
J.E. Bear, T.M. Svitkina, M. Krause, D.A. Schafer, J.J. Loureiro, G.A. Strasser, I.V. Maly, O.Y. Chaga, J.A. Cooper, G.G. Borisy, and F.B. Gertler. Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility. Cell, 109:509–521 (2002).
On microtubule dynamics
I.V. Maly and G.G. Borisy. Self-organization of treadmilling microtubules into a polar array. Trends Cell Biol., 12:462–465 (2002). Online supplement
I.V. Maly. Diffusion approximation of the stochastic process of microtubule assembly. Bull. Math. Biol., 64:213–238 (2002).
I.A. Vorobjev, V.I. Rodionov, I.V. Maly, and G.G. Borisy. Contribution of plus and minus end pathways to microtubule turnover. J. Cell Sci., 112:2277–2289 (1999).
On intracellular transport
I.V. Maly and I.A. Vorobjev. Centrosome-dependent anisotropic random walk of cytoplasmic vesicles. Cell Biol. Int., 26:791–799 (2002).
I.V. Maly. A stochastic model for patterning of the cytoplasm by the saltatory movement. J. Theor. Biol., 216:59–71 (2002).