Contact Information
tel: (610) 758-6835
fax: (610) 758-5057
email: ian.laurenzi@lehigh.edu
www: http://compbiol.che.lehigh.edu

Current Research

Systems Biology

In a given moment of the life of a cell, only a handful of key molecules may be present whereas others may be abundant. That is, the populations of biochemical species may vary over orders of magnitude. Furthermore, the intrinsic rates of chemical association, dissociation and conversion of these species may vary considerably. Therefore, (a) randomness may be manifested in the kinetic time evolution of some biological processes and (b) mathematical descriptions of said processes may be "stiff" due to disparate timescales, and thereby recalcitrant to numerical integration. Dr. Laurenzi is developing chemical models for the kinetics and mechanisms of the vast number of interactions between proteins, DNA, and RNA for use in "stochastic simulation". Unlike molecular simulations such as GCMC and MD, these simulations track the time-evolution of biochemical populations over time, and explicitly account for the effects of "small number statistics". This "in-silico" approach is currently being applied to systems as diverse as gene expression and central metabolism in the baker's yeast S cerevisiae.

Multi-component aggregation-fragmentation phenomena

Due to the mathematical complexity of the traditional deterministic approach to aggregation kinetics, the exact quantification of the time-evolution of batch (constant-volume, spatially-invariant) aggregation-fragmentation processes such as blood coagulation and branched polymerization has been exceedingly difficult to predict. Dr. Laurenzi has developed an algorithm to predict the exact kinetic time evolution of particle aggregation and breakup in systems featuring multiple conservation laws or chemical or biological components. He is applying these techniques to quantify the physical criteria for gelation/precipitation of antibodies with their antigens, blood fibrinogen and blood platelets, and other biological coagulation processes. Please see the papers below for more information.

Receptor-Mediated Adhesion

Platelets - the cells that initiate and mediate clotting and thrombosis - are among the most populous cells in the bloodstream with a concentration of 3x1011 cells/L. Platelet adhesion to the arterial or venous wall is mediated by interactions of cell-membrane-bound glycoproteins such as GPIba with complementary biomolecules such as vwf, which are bound to the endothelium. In 'small systems' such as the contact area between cells where such interactions occur, single-molecule events on the nanoscale translate to macroscopic phenomena, such as adhesion or the passage of current across neurons. Thus, measurement of the kinetics of such events requires a stochastic approach, insofar as rates of complex formation or macromolecular transformation cannot be measured by conventional chemical means. Dr. Laurenzi is employing his expertise in this area with Tom Diacovo (Washington University) to quantify the kinetics of dissociation of blood cell adhesion receptors from their targets and characterize the effects of mutation and biochemical disruption on the adhesive properties of blood cells.

High Throughput Biotechnology

Microarrays are devices that employ the properties of DNA hybridization to determine changes in gene expression on the genome scale. Customarily, each "spot" on a microarray is a pure sample of DNA uniquely complementary to a specific gene sequence. However, it is occasionally observed that mRNA-dervied cDNAs accidentally hybridize to spots intended for other transcripts, in a process known as cross hybridization. Using data-mining and modeling approaches, Dr. Laurenzi is investigating the effects of cross hybridization to create more precise and specific microarray technologies.

Honors and Awards

Pharmaceutical Research and Manufacturers of America Foundation Postdoctoral Fellowship, 2004

NIH Ruth L. Kirschstein National Research Service Award (declined), 2004

Tau Beta Pi, 1996

Phi Beta Kappa, 1995

Rensselaer Award for Academic Excellence, 1995

Selected Publications

J. L. Rinn, J. S. Rozowsky, I. J. Laurenzi, P. H. Petersen, K. Zou, W. Zhong, M. Gerstein, and M. Snyder. Major Molecular Differences between Mammalian Sexes Are Involved in Drug Metabolism and Renal Function. Developmental Cell 6:791-800. 2004.

T. A. Doggett, G. Girdhar, A. Lawshe, J. L. Miller, I. J. Laurenzi, S. L. Diamond, and T. G. Diacovo. Alterations in the intrinsic properties of the GPIba -VWF tether bond define the kinetics of the platelet-type von Willebrand disease mutation, Gly233Val. Blood 102:152-160. 2003.

I. J. Laurenzi and S. L. Diamond. Kinetics of random aggregation-fragmentation processes with multiple components. Phys. Rev. E. 67:051103. 2003.

T. A. Doggett, G. Girdhar, A. Lawsh�, D. W. Schmidtke, I. J. Laurenzi, S. L. Diamond, and T. G. Diacovo. Selectin-like Kinetics and Biomechanics Promote Rapid Platelet Adhesion in Flow: The GPIb-vWF Tether Bond. Biophys. J. 83:194-205. 2002.

Ian J. Laurenzi, John D. Bartels, Scott L. Diamond. A General Algorithm for Exact Simulation of Multicomponent Aggregation Processes. J. Comput. Phys. 177:418-449. 2002.

Ian J. Laurenzi, Scott L. Diamond. Bidisperse Aggregation and Gel Formation via Simultaneous Convection and Diffusion. Ind. Eng. Chem. Res. 41:413-420. 2002.

Ian J. Laurenzi. An analytical solution of the stochastic master equation for reversible bimolecular reaction kinetics. J. Chem. Phys.113:3315-3322. 2000.

Ian J. Laurenzi and Scott L. Diamond. Monte Carlo Simulation of the Heterotypic Aggregation Kinetics of Platelets and Neutrophils. Biophys. J. 77:1733-1746. 1999.