Bree Aldridge



Bree Aldridge

Research Fellow Department of Immunology and Infectious Diseases Harvard School of Public Health [Fortune lab] Postdoctoral mentors: Sarah Fortune and Barry Bloom

aldridgeAThsphDOTharvardDOTedu HMS: WAB444, (617) 432-6910 HSPH: HSPH I 802, (617) 432-7506

Education

Ph.D Biological Engineering, Massachusetts Institute of Technology, 2008 Ph.D. Advisors: Douglas Lauffenburger (Biological Engineering, MIT) and Peter Sorger (Department of Systems Biology, Harvard Medical School)

B.S. Computer Engineering, University of Arizona, 2002 B.S. Molecular and Cellular Biology, University of Arizona, 2002

Research

My research goals focus on understanding the mechanisms which make cellular signaling networks precise yet flexible by combining quantitative single-cell experiments with mathematical analysis and interpretable modeling.

Computational models of signaling pathways are tools that help us quantitatively explore complex signaling networks. One method to decipher entangled signals is to characterize the signals that influence cell decisions. For ordinary differential equation-based models, several methods exist to study steady state signals that lead to different cell fates. However, some signal transduction networks influence cell decisions through transient signals before the network returns to its steady state. We employ computational methodologies augmented from dynamical systems and fluid mechanics to quantitatively analyze transient signals and relate them to different cell fates.

Complexity is another obstacle in understanding signaling pathways. Often, a mechanistic model is too large and intertwined to interpret, even with the aid of analysis tools. We are developing modeling techniques aimed at improving modeling usability and interpretability. We employ logic-based and hyrbid modeling methods that are quantitative, easy to manipulate, and incorporate known and hypothesized signaling interactions.

Publications

"Fuzzy logic analysis of kinase pathway crosstalk in TNF/EGF/Insulin-induced signaling." B.B. Aldridge, J. Saez-Rodriguez, J.L. Muhlich, P.K. Sorger, D.A. Lauffenburger. PLoS Comput Biol 5(4): e1000340. doi:10.1371/journal.pcbi.1000340 (2009). [full text] [MIT spotlight]

"Quantitative analysis of pathways controlling extrinsic apoptosis in single cells." Albeck, J. G., Burke, J. M., Aldridge, B., Zhang, M. S., Lauffenburger, D. A., and Sorger, P. K. Molecular Cell (2008). 30: 11-25. [full text]

"Physicochemical modelling of cell signalling pathways." B. Aldridge, J. Burke, D. Lauffenburger, P. Sorger. Nature Cell Biology. (2006) 8, 1195-2003. [full text] [podcast]

"Direct Lyapunov Exponent Analysis Enables Parametric Study of Transient Signaling Governing Cell Behavior." B. Aldridge, G. Haller. P. Sorger, D. Lauffenburger. Systems Biology (2006) 6, 425-432. [full text.] [Supplementary materials] [SIAM news article]

"Misorientation and reduced stretching of aligned sister kinetochores promote choromosome missegregation in EB1 or APC-depleted cells." V. Draviam, I. Shapiro, B. Aldridge, P. Sorger. EMBO J. (2006) 25, 2814–2827. [full text] [MIT news story]

"Quantitative analysis of the mitochondrial-pathway requirement for receptor-mediated apoptosis." B.B. Aldridge*, S. Gaudet*, D.A. Lauffenburger, P.K. Sorger. (In preparation)

Funding

[DOE Computational Science Graduate Fellowship] [Center for Cell Decision Processes]