Andrew M. Stein Research Overview Improving our understanding of cellular, biomechanical, and physiological processes by 1) creating mathematical models that integrate multiple sources of biological data and 2) developing novel image-processing algorithms to quantify experimental results. Areas of expertise include glioma invasion, chronic myeloid leukemia, tumor growth, cell motility, and biopolymer networks. Experience Novartis – Cambridge, MA, 2009-Present Visiting Scientist • Developed and validated mathematical models for CML. • Explored usefulness of mechanistic models for Type II diabetes in assessing beta-cell function. Institute for Math and its Applications – Minneapolis, MN, 2007-2009 Postdoctoral Fellow Conducted research on the biomechanical properties of tissue engineering scaffolds with Victor Barocas and on mechanical models for cell motility with Hans Othmer. • Developed a finite element mechanical model for artificial tissue constructs and an image-processing algorithm for identifying the 3d architecture of these constructs. By modeling realistic network geometries, we were able to determine the cause of strain stiffening in the tissue constructs and identify a new, critical parameter influencing the network behavior—the cross-link stiffness. • Developed computational framework for cell motility that includes the mechanical interactions between the cell cytoskeleton and its environment. University of Michigan – Ann Arbor, MI, 2003-2007 Graduate Research Assistant Conducted research on the invasion of glioblastoma tumor spheroids with Trachette Jackson and Leonard Sander • Developed mathematical models of tumor invasion, which lead to a novel way to assess invasiveness. Namely, though mathematical analysis, I discovered a new parameter, the shed rate, which gives the rate at which cells detach from the main tumor mass and invade the surrounding tissue. This characterization may ultimately be used as a diagnostic tool which could have the potential to impact treatment strategies. • Developed novel image processing algorithm for automatically measuring the invasiveness of a tumor spheroid. This algorithm is in use at three experimental labs. Novartis – East Hanover, NJ, 2005, 2006 Graduate Intern • Developed integrative model for predicting efficacy of a targeted leukemia drug in individual patients. Model outperformed the standard prognostic indicators. • Developed PKPD model for the effect of an anti-cancer monoclonal antibody on apoptosis biomarker expression. Lear Corporation – Southfield, MI, 2003 Advanced Product Development Intern • Designed support structure for a configurable overhead storage module for cars and trucks. Patent 7052068. • Designed mechanisms and selected materials for a hyperbolic cup holder. Freedman & Goldberg CPAs – Farmington Hills, MI, 2002 Statistical Consultant Advised accountants on statistical techniques for estimating the total amount that an investment company shortchanged its clients. Massachusetts Institute of Technology, 2002 Graduate Research Assistant • Analyzed a differential imaging ultrasound system for detecting breast cancer. • Identified and quantified trade off between shift invariance and depth resolution in imaging systems. Education Ph. D. University of Michigan, Applied Mathematics, 2007 Advisors: Leonard Sander and Trachette Jackson S. M. MIT, Mechanical Engineering, 2002 Advisor: George Barbastathis S. B. MIT, Mechanical Engineering, 2000 Publications 1. Sander, E. A., Stein, A. M. Swickrath, M., Barocas, V. A.. Out of many, one: Modeling schemes for biopolymer and biofibril networks. Trends in Computational Nanomechanics: Transcending Space and Time. Springer, Heidelberg, 2009. 2. Stein A. M., Vader, D. A., Weitz, D. A., Sander, L. M., The micromechanics of collagen-I gels. arXiv, 0807.2805. 3. Stein, A. M., Vader, D. A., Jawerth, L. M, Sander, L. M., Weitz, D. A., An algorithm for extracting the network geometry of three-dimensional collagen gels. J. Microscopy, 232 (3) 463-475 4. Nowicki, M. O., Dmitrieva, N., Stein, A. M., Cutter, J., Godlewski, J., Saeki Y., Nita, M., Berens, M. E, Sander, L. M., Newton, E., Chiocca, E. A., Lawler, S. E. Lithium inhibits invasion of glioma cells; possible involvement of glycogen synthase kinase-3. Neuro-Oncol, 10(5):690–9, 2008. 5. Stein, A. M., Nowicki, M. O., Demuth, T., Berens, M. E., Lawler, S. E., Chiocca, E. A., Sander. L. M., Estimating the cell density and invasive radius of 3d glioblastoma tumor spheroids grown in vitro. Applied Optics, 46(22):5110–5118, 2007. 6. Stein, A. M., Demuth, T., Mobley, D. Berens, M., Sander, L. M. A mathematical model of glioblastoma tumor spheroid invasion in a three-dimensional in vitro experiment. Biophys. J., 92:356–365 (2007). 7. Stein, A. M., Vader, D. A., Deisboeck, T. S., Chiocca, E. A. Sander, L. M., Weitz, D. A., Directionality of glioblastoma invasion in a 3d in vitro experiment. arXiv, 0610031 (2006). 8. Stein, A. M., Vader, D. A., Sander, L. M., Weitz, D. A., Stochastic models of glioblastoma invasion In: Mathematical Modeling of Biological Systems. Vol. I, edited by Deutsch, A. et. al., Birkhauser, Boston (2006). 9. Khain, E, Sander, L. M., Stein, A. M. A model for glioma growth. Complexity. 11, 53-57 (2005). 10. Stein, A. Barbastathis, G. Axial imaging necessitates loss of lateral shift invariance, Applied Optics: Information Processing. 41 6055-6061 (2002). Patents 7052068 – Configurable overhead console for cars and trucks. Presentations Mathematical Biosciences Institute (Columbus, OH) September, 2008 Cell motility through 3d collagen-I gels. European Conference for Math. And Theor. Biol. (Edinburgh, UK) July, 2008 The micromechanics of collagen-I gels. Society for Mathematical Biology (San Jose, CA) August, 2007 The micromechanics of collagen-I gels. MCTP/ICAM Biomechanics Workshop, June, 2007 The micromechanics of collagen-I gels. M.D. Anderson Cancer Center (Houston, TX) January, 2007 Models for glioblastoma invasion. U. Michigan/Michigan State Mathematical Biology Day, December, 2006 Models for glioblastoma invasion. SIAM Life Sciences/SMB (Raleigh, NC) July, 2006
Describing glioblastoma invasion in a 3d in vitro experiment using mathematical model of motility, shedding, and proliferation Complex Systems Academic Workshop (Ann Arbor, MI) October, 2005 Cellular autonoma models for glioblastoma invasion. European Conference for Math. and Theor. Biol. (Dresden, Germany) July, 2005 Models for invasion of malignant brain cancer in an in vitro experiment Mathematical Biology Seminar (Ann Arbor, MI) February, 2005 Partial differential equation models for invasion of malignant brain cancer. ICIS (Albuquerque, NM) November 2001 1) Detection of tumor growth from differential acoustic measurements,
2) Axial imaging necessitates loss of lateral shift invariance Posters American Conference of Pharmacology (Mashantucket, CT) October 2009 Inference of imatinib (IM) effects on leukemic stem cell (SC) compartment via mathematical modeling of IRIS treatment response data. Microrheology Workshop (Los Angeles, CA) September 2007 The Micromechanics of Collagen-I gels. Biomedical Engineering Society Fall Meeting (Los Angeles, CA) September 2007 Collagen-I gel micromechanics Workshop for Young Researchers in Math Bio. (Columbus, OH) March 2007 Models for collagen-I gel micromechanics Cancer Symposium (Ann Arbor, MI) November, 2005 Stochastic models for glioblastoma invasion. Society for Mathematical Biology (Ann Arbor, MI) July, 2004 Models for malignant brain cancer invasion. Teaching Calculus I (University of Michigan), Fall, 2005 Engineering Concepts (Boston Academy), Summer, 2001 Professional Activities Reviewed for: Cancer Letters, Biophysical Journal, Journal of Theoretical Biology Society Memberships Biomedical Engineering Society Biophysical Society European Society for Mathematical and Theoretical Biology Society for Mathematical Biology Workshops and Conferences Americance Conference of Pharmacology (Mashantucket, CT) October 2009 Multiscale Methods in Biology (MBI – Ohio State) November 2008 Cell and Tissue Movement (MBI – Ohio State) September 2008 ECMTB (Edinburgh, UK), July, 2008 Microrheology Workshop (Los Angeles, CA) January 2008 Biomedical Engineering Society Fall Meeting (Los Angeles, CA), October 2007 IMA – Molecular and Cellular Biology (Minneapolis, MN), 2007-2008 Society for Mathematical Biology (San Jose, CA), August 2007 Summer Bioengineering Conference (Keystone, CO), June 2007 MCTP/ICAM Biomechanics Workshop (University of Michigan), June 2007 Workshop for Young Researchers in Math Bio. (MBI – Ohio State), March 2007 SIAM Life Sciences / SMB (Raleigh, NC). August 2006 IPAM Angiogen.. Neovasc. and Morphogen. (Los Angeles, CA), May 2006 AMS Regional Meeting (South Bend, IN), April, 2006 Cancer Symposium (Ann Arbor, Michigan), November, 2005 ECMTB (Dresden, Germany), July, 2005 Dynamics of Cancer: Modeling and Experiment (U. Michigan), May, 2005 Society for Mathematical Biology (University of Michigan), July, 2004 SIAM Annual Meeting/Life Sciences (Portland, OR), July, 2004 Complex Systems Summer School (Santa Fe Institute), June, 2002 ICIS (Albuquerque, NM), Nov., 2001 NIPS (Boulder, CO), Dec., 2000