February 13, 2014
Munzer Auditorium

Jan Liphard, PhD

Associate Professor
Department of Biomedical Operations
Stanford University

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Interplay of Genes, Anatomy, and Tissue Mechanics in Cancer
Abstract:

As of last count, there are at least 10 risk factors for breast cancer. Some of these risk factors are genetic, such as mutations in the BRCA1 and 2 genes. Other risk factors are based on bulk tissue characteristics such as the degree to which the tissue attenuates x-rays ("mammographic density"). Finally, risk and outcomes are also correlated with tissue mechanics and specific micro-anatomical features, such as collagen lines or tracts that extend radially outwards from the tumor-stromal interface. Despite significant progress in discovering risk factors, it is not understood if and how these risk factors interact. We have developed a simple model system for studying the interplay of genes, mechanics, and geometry in the transition to invasive phenotypes. We have found that pairs or groups of Ras-transformed mammary acini with thinned basement membranes and weakened cell-cell junctions can generate collagen lines that then coordinate and accelerate transition to an invasive phenotype. When two or more acini mechanically interact by collagen lines, the pairs or groups of acini begin to disorganize rapidly and in a spatially coordinated manner, whereas acini that do not interact mechanically with other acini disorganize slowly and to a lesser extent. When acini were mechanically isolated from other acini and also from the bulk gel by directed laser cutting of the collagen matrix, transition to an invasive phenotype was blocked in 20 of 20 experiments. Thus, pairs or groups of mammary acini can interact mechanically over long distances through the collagen matrix and these directed mechanical interactions are necessary for rapid transition to an invasive phenotype.

Reference:

Rapid disorganization of mechanically interacting systems of mammary acini
Q. Shi, RP. Ghosh, H. Engelke, CH. Rycroft, L. Cassereau, JA. Sethian, VM. Weaver, and J. Liphardt

PNAS 111(2), 658-663 (2014)

April 10, 2014
Munzer Auditorium

Michael Strano, PhD

Professor
Department of Checmical Engineering
Massachusetts Institute of Technology

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New Concepts in Biosensing using Single Walled Carbon Nanotubes and Graphene
Abstract:

Our lab at MIT has been interested in how the 1D and 2D electronic structures of carbon nanotubes and graphene respectively can be utilized to advance new concepts in molecular detection. We introduce CoPhMoRe or corona phase molecular recognition1 as a method of discovering synthetic antibodies, or nanotube-templated recognition sites from a heteropolymer library. We show that certain synthetic heteropolymers, once constrained onto a single-walled carbon nanotube by chemical adsorption, also form a new corona phase that exhibits highly selective recognition for specific molecules. To prove the generality of this phenomenon, we report three examples of heteropolymers–nanotube recognition complexes for riboflavin, L-thyroxine and estradiol. The platform opens new opportunities to create synthetic recognition sites for molecular detection. We have also extended this molecular recognition technique to neurotransmitters, producing the first fluorescent sensor for dopamine. Another area of advancement in biosensor development is the use of near infrared fluorescent carbon nanotube sensors for in-vivo detection2. Here, we show that PEG-ligated d(AAAT)7 DNA wrapped SWNT are selective for nitric oxide, a vasodilator of blood vessels, and can be tail vein injected into mice and localized within the viable mouse liver. We use an SJL mouse model to study liver inflammation in vivo using the spatially and spectrally resolved nIR signature of the localized SWNT sensors. Lastly, we discuss graphene as an interfacial optical biosensor, showing that it possesses two pKa values in alkaline and basic ranges. We use this response to measure dopamine in real time, spatially resolved at the interface with living PC12 cells which efflux dopamine, indicating graphene’s promise as an interfacial sensor in biology.

1. Zhang, JQ et. al. Molecular recognition using corona phase complexes made of synthetic polymers adsorbed on carbon nanotubes. Nature Nanotechnology, 8, 12, 2013, 959-968
2. Iverson, NM, et. al. In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes. Nature Nanotechnology, 8, 11, 2013, 873-880

September 11, 2014
Munzer Auditorium

Paul Yager, PhD

Professor
Department of Bioengineering
University of Washington

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Integration of Paper Microfluidic Methods for Detection of Infectious Diseases for Low Resource Settings
Abstract:

Two-dimensional paper networks (2DPNs) are a new class of devices that allow complex chemical processing in a very low-cost format. We have, for the last 6 years, been learning how to translate what we have learned about point-of-care diagnostic technologies in conventional microfluidics into the language of porous media. The wicking of fluids in porous materials (like paper, nitrocellulose membranes, etc.) allows us to discard pumps, which permits great savings in complexity and cost, and the potential to perform complex tests without any permanent instruments. However, there are many physical and chemical differences between open ducts and porous media--we have put a good deal of effort into understanding the performance and design rules of simple paper systems. Currently, the two primary applications for this technology in our lab are for detection of pathogens that cause human infectious disease: 1) highly-sensitive multiplexed protein binding assays (of which immunoassays are a class) for detection of influenza, and 2) ultrasensitive rapid multiplexed isothermal nucleic acid amplification assays for detection of pathogens by DNA and RNA. All assays are designed to operated by untrained users in low resource settings (e.g. include the home), and employ visible optical readout that can be captured and quantified using camera-equipped cellular phones.

October 9, 2014
Munzer Auditorium

Min Yu, MD, PhD

Assistant Professor
Stem Cell Biology and Regenerative Medicine
Univeristy of Southern California

Characterizing circulating tumor cells: Insights into Cancer Metastasis

Abstract:

Circulating tumor cells (CTCs), shed from primary and metastatic tumors into blood stream, contain potential rare cancer stem cells or metastasis-initiating cells. Using our microfluidic CTC-chips, we have analyzed characteristics of CTCs in both mouse cancer models and human cancer patients. We have discovered an important WNT2-TAK1 pathway in promoting pancreatic cancer metastasis via enhanced resistance to anoikis, and demonstrated evidence of epithelial mesenchymal transition (EMT) in CTCs isolated from breast cancer patients. We have recently developed in vitro culture of CTCs, enabling in depth analysis of their molecular properties using next-generation sequencing and pilot drug sensitivity testing.

November 13, 2014
Munzer Auditorium

Daniel T. Chiu, PhD

Endowed Professor in Analytical Chemistry
Professor of Bioengineering
Department of Chemistry
University of Washington

Highly fluorescent semiconducting polymer dots for biology and medicine
Abstract:

Semiconducting polymer nanoparticles have attracted considerable attention in recent years because of their outstanding characteristics as fluorescent probes. These nanoparticles, which primarily consist of conjugated polymers and are called polymer dots (Pdots) when they exhibit small particle size and high brightness, have demonstrated utility in a wide range of applications such as fluorescence imaging and biosensing. In this presentation, I will highlight work in my lab in the development of Pdots for biological detection and imaging.

December 11, 2014

Lance Liotta, MD, PhD

Professor
College of Science
George Mason University

Protein Painting: A novel affinity technology maps hidden drug targets in protein-protein interactions: applications to diagnosis and therapy
Abstract:

We have identified a new class of small organic molecules that bind proteins with extremely high affinity. We use these affinity molecules to create two novel technologies:

A) Protein Painting, a technology for rapidly sequencing, with very high specificity, the contact regions between native interacting proteins. We introduce Protein Painting to discover contact regions between two and three-way protein-protein signaling interactions and then apply this information to create peptides and monoclonal antibodies that block the interaction and abolish cell signalling. The technology is broadly applicable to discover protein interaction drug targets.

B) Smart nano cages (nano traps) to discover and accurately measure previously invisible biomarkers that exist at a low concentration thousands of times lower than detectable by conventional technology. Nanotraps are used to develop new broad classes of clinical diagnostic tests that reach previously unattainable levels of sensitivity and precision.