2013 Nanobiotechnology Seminar Series

Jan 10, 2013
Munzer Auditorium

David Haussler, PhD
Investigator, Howard Hughes Medical Institute
UCSC Distinguished Professor of Biomedical Engineering,
University of California, Santa Cruz
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Cancer Genomics

Abstract:

Throughout life, the cells in every individual accumulate many changes in the DNA inherited from his or her parents. Certain combinations of changes lead to cancer. During the last decade, the cost of DNA sequencing has been dropping by a factor of 10 every two years, making it now possible to read most of the three billion base genome from a patient’s cancer tumor, and to try to determine all of the thousands of DNA changes in it. Under the auspices of NCI’s Cancer Genome Atlas Project, 10,000 tumors will be sequenced in this manner in the next few years. Soon cancer genome sequencing will be a widespread clinical practice, and millions of tumors will be sequenced. A massive computational problem looms in interpreting these data.

First, because we can only read short pieces of DNA, we have the enormous problem of assembling a coherent and reliable representation of the tumor genome from massive amounts of incomplete and error-prone evidence. This is the first challenge. Second, every human genome is unique from birth, and every tumor a unique variant. There is no single route to cancer. We must learn to read the varied signatures of cancer within the tumor genome and associate these with optimal treatments. Already there are hundreds of molecularly targeted treatments for cancer available, each known to be more or less effective depending on specific genetic variants. However, targeting a single gene with one treatment rarely works. The second challenge is to tackle the combinatorics of personalized, targeted, combination therapy in cancer.

Feb 14, 2013
Munzer Auditorium

Mostafa A. El-Sayed, PhD
Julius Brown Chair and Regents Professor
Director, Laser Dynamics Laboratory,
Department of Chemistry and Biochemistry,
Georgia Institute of Technology

Using biochemical-targeting methods, one can conjugate the plasmonic nanoparticles to many parts of the cell, healthy or sick. Since the nanoparticles have comparable size to many parts of the cell, binding plasmonic (or nonplasmonic) nanoparticles to parts of the cell could change its properties including curing, or, most likely, killing sick cells. Using plasmonic nanoparticles has the advantage of using their enhanced scattering properties to image the response of the cells1-3 (including death) to the effect of binding the nanoparticles to selected part of the cell. Not only one can image the response of the cells directly bound to the nanoparticles but also the reaction of the community of the surrounding nanoparticle-free cells
     

In order to gain intra-cell molecular information, and thus molecular cell mechanisms instead of just global cell information, we were recently able4 to record the enhanced molecular Raman vibration spectra (SERS) of molecules anywhere in the cell during the full cell cycle, from birth to division. Furthermore, if we give the cells cancer drugs, we can determine the time of the cell death. The potential future applications of this technique of PLASMONIC ENHANCED MOLECULAR CELL IMMAGING (PEMCI) in molecular cell biology, in drug testing, in determining drug action and cell death mechanisms will be discussed.

References:

(1) Kang, B.; Mackey, M.A.; El-Sayed, M.A. J. Am. Chem. Soc Comm.2010, 132, 1517
(2) Austin, L.; Kang, B.; Yen, C.-W.; El-Sayed, M. A. J. Am. Chem. Soc. Comm. 2011, 133, 17594.
(3) Austin, L. A.; Kang, B.; Yen, C.-W.; El-Sayed, M. A. Bioconjugate Chem. 2011, 22, 2324.
(4)    Kang, Bin; Austin, Lauren A. and El-Sayed, Mostafa A.; Real-Time Molecular Imaging throughout the Entire Cell Cycle by Targeted Plasmonic-Enhanced Rayleigh/Raman Spectroscopy, , Nano Lett., 2012, 12 (10), pp 5369–5375.

Mar 14, 2013
Munzer Auditorium

Judith Luborsky, PhD
Professor
Associate Dean for Research, College of Health Sciences
Department of Obstetrics and Gynecology,
Rush University
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The significant proportion of cancer mortality is associated with ovarian cancer in the United States.  Our work addresses the continuing need to better detect, understand and control this disease, by studying both human ovarian cancer and a novel animal model, the egg-laying hen.  The susceptibility and etiology for cancer appears to be multi-factorial and may include a combination of genetic, epigenetic, environmental and chronic inflammatory effects [3-7], although the specific sequence and relative roles are not well defined for many cancers, including ovarian cancer. There is accumulating evidence that autoimmunity and chronic inflammation contribute significantly to cancer progression. We showed there is an autoimmune disease of the ovary and that the same autoantibodies (e.g. anti-mesothelin and others) are found in both women with infertility and ovarian cancer.  This is consistent with the well known epidemiologic evidence that infertility has a risk of ovarian cancer.  In order to examine these relationships further, we used the egg-laying hen, which spontaneously develops progressive ovarian cancer at a high rate.  The same autoantibodies as found in humans (including anti-p53) are detected in longitudinal studies.  These results suggest the hen model may facilitate the pre-clinical development of detection tests and of treatments to arrest or prevent ovarian tumors.

The singular term “cancer” is never one kind of disease, but deceivingly encompasses a large number of heterogeneous disease states, which makes it impossible to completely treat cancer using a generic approach. Rather systems approaches are urgently required to assess cancer heterogeneity, stratify patients and enable the most effective, individualized treatment. Intratumoral heterogeneity is a reflection of hierarchical complexity and dynamic evolution of tumor microenvironment. To identify all the cellular components, including both tumor and infiltrating immune cells, and to delineate the associated cell-to-cell signaling network that dictates tumor initiation, progression and metastasis, we developed a suite of single cell technologies that has the great potential to probe heterogeneous tumor cells and their microenvironment from small quantities of tumor tissues. The first is a microfluidic chip that combines ultra-high density antibody barcodes and a sub-nanoliter microchamber array to perform high-throughput,45-plex profiling of proteins secreted from single cells. It has been applied to the measurement of human macrophage cells and single glioblastoma cells from patients. The results reveal profound cellular heterogeneity in terms of secretomic signature. The second platform being developed allows us to decipher the conversation between tumor and stromal cells at the single-cell level and the result suggests a new route to anti-cancer therapy by targeting microenvironmental components and inter-cellular signaling pathways. The third platform enables functional genomic analysis of tumor cells at the whole genome-scale and the single-cell level. These single-cell analysis technologies will allow for comprehensive delineation of lineage relationship and gene regulatory network associated with tumor evolution, and shed new light on cancer stratification and therapy.  

Cancer metastasis through the bloodstream is facilitated by adhesive interactions between circulating tumor cells (CTCs) and the blood vessel wall. My laboratory has used a combination of experiments in flow chambers and living mice, and multiscale computational models, to understand the behavior of blood and cancer cells under physiological flow conditions. We have identified some of the critical enzymes and surface proteins that control the fate of CTCs in the bloodstream, and how the local microenvironment surrounding tumor cells can alter their adhesiveness under flow. Thin coatings of halloysite nanotubes represent a remarkable new biomaterial capable of capturing rare CTCs from patient blood samples while simultaneously repelling most white blood cells. We have explored the use of halloysite coatings, in conjunction with targeted nanoscale liposomes loaded with the cancer drug doxorubicin, to selectively kill CTCs found within blood. Finally, studies are underway to determine the physical mechanisms that allow fluid shear stress to increase the susceptibility of tumor cells to the apoptosis drug TRAIL.

Small nanoparticles (30-50 nm) containing an amorphous precipitate of calcium phosphate with a wrapping lipid bilayer have been developed to deliver impermeable drugs and genes to intracellular targets. Plasmid DNA, siRNA, peptide antigen and small chemo drugs have been delivered with the LCP to tumor and liver. Both mechanism and application of the nanoparticles will be discussed.

Sept 12, 2013
TBD

Hyongsok (Tom) Soh, PhD
Ruth Garland Endowed Chair, Departments of Mechanical Engineering and Materials, University of California Santa Barbara

Oct 10, 2013
TBD

Michal J. Cima, PhD
David H. Koch Professor of Engineering,
Faculty Director, Lemelson-MIT Program
Department of Materials Science and Engineering,
Massachusetts Institute of Technology

Nov 14, 2013
TBD

Samir Iqbal, PhD
Assistant Professor, Department of Electrical Engineering and Bioengineering (Courtesy),
Nanotechnology Research and Education Center,
University of Texas at Arlington

Dec 12, 2013
TBD

Ian Baker, PhD
Sherman Fairchild Professor Engineering, Senior Associate Dean for Academic Affairs, Thayer School of Engineering,
Dartmouth College