The Tanner lab has determined that cells can switch between different types of motility namely rotation, random and amoeboid when placed in 3D biomimetic platforms. We have linked the type of motility to the establishment of distinct multicellular architectures and tissue polarity. The mechanisms establishing and controlling tissue polarity are central both to normal tissue function and disease. However, the fundamental biophysical processes by which a single cell must undergo multiple rounds of mitosis to assemble into polarized tissue-like structures remain elusive. We go a step further to link the lessons learned from epithelial morphogenesis to dissect the physico-chemical mechanisms underlying de novo tumor organogenesis.
We seek to link the lessons learned from epithelial morphogenesis to dissect the mechanisms by which tumor cells can colonize distant organs by directly visualizing single cell dynamics in thick tissues. By treating newly-formed neoplasms as new organs, we aim to dissect the physico-chemical processes involved in this de novo “tumor organogenesis”. Our analysis of epithelial morphogenesis using live imaging has revealed that cells can undergo three-dimensional (3D) specific motility to assemble into multicellular tissues. Our group seeks to uncover how adult cells sense a change in dimension and then conveys that to its progeny to understand the mechanisms by which an adult cell can use these different motilities to remodel existing tissue architecture. To quantify minute forces, the laboratory utilizes a battery of biophysical and molecular approaches: optical tweezers, multi-photon microscopy, sub-cellular protein visualization in fixed and living cells and tissues, fluctuation correlation data analysis, and mathematical modeling of complex cell dynamics within thick tissues. Furthermore, we link in vitro findings to clinically relevant problems by studying animal models.
In Project 1, we focus on visualizing the types of motility that can be executed by tumor cells in 3D biomimetic matrices. We then aim to determine the molecular and physical regulators that govern what type of motility is executed.
In Project 2, we focus on the dynamics of remodeling of the de novo ECM: “soil” in the brain. Here, we probe the interplay between motility and secretion and de novo assembly of ECM proteins in 3D biomimetic platforms for metastasis.
In Vivo Tissue has Non-linear Rheological Behavior Distinct from 3D Biomimetic Hydrogels as Determined by AMOTIV Microscopy.Biomaterials. Accepted, 2015. [ Journal Article ]
- Adv Mater. [Epub ahead of print - Nov. 9], 2015. [ Journal Article ]
- Science Trans. Med. 7: 283ps9, 2015. [ Journal Article ]
- Proc. Natl. Acad. Sci. U.S.A. 109: 1973-8, 2012. [ Journal Article ]
Deconstructing the role of the ECM microenvironment on drug efficacy targeting MAPK signaling in a pre-clinical platform for cutaneous metastatic melanoma.Biomaterials. 56: 129-39, 2015. [ Journal Article ]
Kandice Tanner received her doctoral degree in Physics at the University of Illinois, Urbana-Champaign under Professor Enrico Gratton. She completed post-doctoral training at the University of California, Irvine specializing in dynamic imaging of thick tissues. She then became a Department of Defense Breast Cancer Post-doctoral fellow jointly at University of California, Berkeley and Lawrence Berkeley National Laboratory under Dr. Mina J. Bissell. Dr. Tanner joined the National Cancer Institute as a Stadtman Tenure-Track Investigator in July, 2012, where she integrates concepts from molecular biophysics and cell biology to learn how cells and tissues sense and respond to their physical microenvironment, and to thereby design therapeutics and cellular biotechnology. For her work, she has been awarded the 2013 National Cancer Institute Director’s Intramural Innovation Award, the 2015 NCI Leading Diversity award, 2016 Federal Technology Transfer Award, the 2016 Young Fluorescence Investigator award from the Biophysical Society and named as a Young Innovator in Cellular and Molecular Bioengineering, which highlight her scientific accomplishments and service to the greater intramural NIH and extramural scientific community. She also maintains strong connections with the extramural community through service as an editorial board member of Scientific Reports and as a review editor for Frontiers in Cell and Development Biology. She currently serves on the Membership Committee of the American Society of Cell Biology, the Minority Affairs Committee of the Biophysical Society and is a Member at large for the Division of Biological Physics of the American Physical Society.
|Alexus Devine B.S.||Postbaccalaureate Fellow|
|King Leung Fung Ph.D.||Research Biologist (Contr.)|
|Colin Paul Ph.D.||Postdoctoral Fellow (CRTA)|
|Jack Rory Staunton Ph.D.||Postdoctoral Fellow (CRTA)|