Assistant Professor of Pathology

Assistant Professor Computational Biology Laboratory Beth Israel Deaconess Medical Center Harvard Medical School
330 Brookline Avenue, RN-231
Boston, MA 02215
Tel: 617-667-0637
Email: kbentley@bidmc.harvard.edu

Website: http://cvbr.hms.harvard.edu/researchers/bentley.html

Lab Size: Between 5 and 10

Summary

The Bentley lab is multidisciplinary, integrating in silico, in vitro and in vivo approaches to develop a dynamic, single to collective cell understanding of blood vessel growth in health and disease. We have a particular focus on understanding how abnormal vessels form in diseases such as in diabetic retinopathy (which causes blindness) and cancer.

For simulation we draw on concepts and approaches from the adaptive systems/evolutionary robotics fields, developing hybrid agent-based models alongside other spatiotemporal modeling approaches. These help us to untangle the complex cell signaling, shape and movement dynamics as cells coordinate and compete during vascular morphogenesis.

We perform experiments to test our model predictions using in vitro cell culture experiments such as live imaging of blood vessel sprouting assays and analysis of vascular patterning in different in vivo mouse models. We are developing a new cutting edge light-sheet microscopy imaging method alongside novel image analysis methods to reveal cell dynamic changes and three-dimensional morphometrics of the vasculature in disease conditions.

Our approach revealed that Notch negative feedback interplays with positive feedback pathways to generate different collective endothelial cell movement during blood vessel growth under normal and disease conditions. We recently validated model predictions in vivo uncovering the first elements of a differential adhesion based mechanisms driving cell rearrangements during blood vessel growth. We are investigating whether abnormal cell dynamics and oscillatory behavior may cause vascular malformations and how these may be targeted by new therapeutics.

 

Publications

  1. K Bentley, A. Philippides, E. Regan. Do endothelial cells dream of eclectic shape? Developmental Cell. 29 (2), 146-158 (2014).
  2. K. Bentley, C.A. Franco, A. Philippides, R. Blanco, M. Dierkes, V. Gebala, F. Stanchi, M. Jones, I. M. Aspalter, G. Cagna, S. Kutschera, L. Claesson-Welsh, D. Vestweber, H. Gerhardt* (2014). The role of differential VE-cadherin dynamics in cell rearrangements in angiogenesis. Nature Cell Biology. 16,309–321 (2014).
  3. K. Bentley, M. Jones, B. Cruys. Predicting the Future: towards symbiotic computational and experimental research in angiogenesis. Experimental Cell Research Journal 319 pp. 1240-1246 (2013).
  4. K. Bentley, G. Mariggi, H. Gerhardt, and P. A. Bates*. Tipping the balance: Robustness of Tip Cell Selection, Migration and Fusion in Angiogenesis. PLoS Computational Biology. 5(10): e1000549.doi:10.1371/journal.pcbi.1000549 (2009).
  5. K. Bentley, H. Gerhardt and P. A. Bates*. Agent-based simulation of notch mediated tip cell selection in angiogenic sprout initialization. Journal of Theoretical Biology, 250(1):25-36. (2008).