Ivan V. Maly

Assistant Professor of Computational Biology

Office: BST3-3090 (3501 Fifth Ave. Pittsburgh PA 15260)

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 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 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.

Group

Sergey N. Arkhipov, PhD, Postdoctoral Associate (cell biology and microscopy)

MunJu Kim, PhD, Research Associate (biomechanics)

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

Alexei S. Mikhailov, MS, Research Scholar (biophysics and microscopy)

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).

Affiliations

Department of Computational Biology, University of Pittsburgh School of Medicine

Center for Bioimage Informatics at Carnegie Mellon University

Joint Pitt-CMU Graduate Program in Computational Biology

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, 2003, with D. A. Lauffenburger

In the present position since 2004

Publications

Most recent

I.A. Vorobjev and I.V. Maly. On the relation of the microtubule length and dynamics: boundary effect and properties of an extended radial array. Cell Tissue Biol. (in press).

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).

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. Eng., 32:1319–1335 (2004).

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).

Updated March 11, 2008