Ivan V. Maly

Assistant Professor

Department of Computational and Systems Biology

University of Pittsburgh School of Medicine

3501 Fifth Ave. Rm. BST3-3090, Pittsburgh PA 15260

Telephone: 412-648-7771

Email: maly at 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 intracellular transport, cytoskeleton dynamics, and cell signaling.

We are especially interested in mechanisms of structural polarization of T cells during immune response. Beyond the more widely known molecular recognition, this cellular mechanism makes elimination of infected and malignant cells precisely targeted. It is similarly crucial to induction of immunological memory, and to stimulation of antibody production. At the same time, certain viruses attacking the immune system itself exploit T cell polarization for their propagation.

The paradoxical situation characteristic of today’s cell science in general is observed also in this area of study: significant advances are being made in identification of proteins that are involved in regulation of the structural polarization in T cells, yet the basic mechanism of the process itself remains essentially unknown 30 years after its first phenomenological description. This paradox suggests that much will be learned when the basic mechanism is elucidated – not only how T cells establish functional polarity, but also how to approach those most basic mechanisms of cellular processes that proved “tough nuts” in other areas of cell biology.

To this aim, we are attempting to integrate the results of other students of T lymphocyte polarization and attack the problem head-on, combining the power of multidimensional live-cell microscopy and computer modeling. Computational modeling in our approach is employed to test quantitative consistency and feasibility of various interpretations of data, as well as to inform and guide further experimentation. Thus, hypotheses of greater (and hopefully, adequate) complexity can be formulated and tested than would be possible without numerical modeling.

Besides being a test-bed for the new, quantitative methodology in fundamental biological research, deciphering this mechanism essential for specificity of immune response is a step towards building future predictive higher-level models of human physiology and pathology.

Vita

Diploma in Physiology, Moscow State University, 1999, with I. A. Vorobjev

Ph.D. in the Life Sciences, Northwestern University, 2002, with G. G. Borisy

Postdoctoral studies in Biological Engineering, Massachusetts Institute of Technology, with D. A. Lauffenburger

In the present position since 2004

Funding

"Quantitative Study of T-Cell Polarization", R01 grant from National Institutes of General Medical Sciences, of Biological Imaging and Bioengineering, and of Allergy and Infectious Diseases.

"Spatial Organization of Cadherin Junctions by Dynamic Microtubules: An Integrated Model", program grant from Human Frontier Science Program, with A. Akhmanova (Rotterdam), N. Brown (Cambridge), and A. Yap (Brisbane).

Group

MunJu Kim, PhD, Research Associate (biomechanics)

Arie Baratt, PhD, Research Associate (physics, mathematical modeling of biological systems)

Eugenie Katrukha, PhD/Cand.Phys.Math.Sci., Postdoctoral Associate (spatial kinetic models of the cytoskeleton)

Qin Yang, PhD, Research Associate (cell immunology)

Liang Zheng, Research Specialist (cell immunology)

Recent graduate: Arpit Tandon, MS in Computational Biology

Publications

(over 600 citations since 2001)

Books

I.V. Maly. Cytoskeleton and Cell Motility Models: From Kinetics to Structure. VDM, 2009 (on Amazon).

Systems Biology, I.V. Maly, ed. (Methods in Molecular Biology vol. 500) Springer, 2009 (on Amazon).

Book chapter

I.V. Maly. Introduction: a practical guide to the systems approach in biology. Methods Mol. Biol. 500:3–13 (2009).

Most recent journal articles: T-cell polarization and related topics

MJ Kim and I.V. Maly. Deterministic mechanical model of T-killer cell polarization reproduces the wandering of aim between simultaneously engaged targets. PLoS Comput. Biol., 5: e1000260 (2009).

A. Baratt, S.N. Arkhipov, and I.V. Maly. An experimental and computational study of effects of microtubule stabilization on T-cell polarity. PLoS ONE, 3:e3861 (2008).

I.A. Vorobjev and I.V. Maly. Microtubule length and dynamics: Boundary effect and properties of extended radial array. Cell Tissue Biol., 2:272–281 (2008). (Russian version here.)

S.N. Arkhipov and I.V. Maly. Retractile processes in T lymphocyte orientation on a stimulatory substrate: morphology and dynamics. Phys. Biol., 5:016006 (2008).

S.N. Arkhipov and I.V. Maly. A model for the interplay of receptor recycling and receptor-mediated contact in T cells. PLoS ONE, 2:e633 (2007).

I. Grigoriev, D. Splinter, N. Keijzer, P.S. Wulf, J. Demmers, T. Ohtsuka, M. Modesti, I.V. Maly, F. Grosveld, C.C. Hoogenraad, and A. Akhmanova. Rab6 regulates transport and targeting of exocytotic carriers. Dev. Cell, 13:305–314 (2007).

S.N. Arkhipov and I.V. Maly. Quantitative analysis of the role of receptor recycling in T cell polarization. Biophys. J., 91:4306–4316 (2006).

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).

Earlier journal articles on cell signaling, the cytoskeleton, and motility

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. Eng., 32:1319–1335 (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, 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).

I.V. Maly and G.G. Borisy. Self-organization of treadmilling microtubules into a polar array. Trends Cell Biol., 12:462–465 (2002). Correct link to supplementary material

I.V. Maly and I.A. Vorobjev. Centrosome-dependent anisotropic random walk of cytoplasmic vesicles. Cell Biol. Int., 26:791–799 (2002).

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).

I.V. Maly. A stochastic model for patterning of the cytoplasm by the saltatory movement. J. Theor. Biol., 216:59–71 (2002).

I.V. Maly. Diffusion approximation of the stochastic process of microtubule assembly. Bull. Math. Biol., 64:213–238 (2002).

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).

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).

Updated February 4, 2010