2013 Nanobiotechnology Seminar Series
Seminar & Discussion 5:30 - 6:30 pm
Reception 6:30 - 6:50 pm
January 10, 2013
David Haussler, PhD
Investigator, Howard Hughes Medical Institute
UCSC Distinguished Professor of Biomedical Engineering,
University of California, Santa Cruz
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.
February 14, 2013
Mostafa A. El-Sayed, PhD
Julius Brown Chair and Regents Professor
Director, Laser Dynamics Laboratory,
Department of Chemistry and Biochemistry,
Georgia Institute of Technology
Nanotechnology Meets Biology in the Cancer Cell
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.
(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.
March 14, 2013
Judith Luborsky, PhD
Associate Dean for Research, College of Health Sciences
Department of Obstetrics and Gynecology,
Novel Autoantibodies May Predict Human and Chicken Ovarian Cancer
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.
April 11, 2013
Rong Fan, PhD
Assistant Professor, Department of Biomedical Engineering, Yale University
Single Cell Technnology for Systems OncoBiology
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.
May 16, 2013
Michael King, PhD
Associate Professor, Department of Biomedical Engineering, Cornell University
Rolling in the Deep: Tumor Cell Adhesion and Treatment in the Bloodstream
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.
May 17, 2013
Leaf Huang, PhD
Fred Eshelman Distinguished Professor
Eshelman School of Pharmacy
UNC, Chapel Hill
Lipid-Calcium Phosphate (LCP) Nanoparticles for Drug and Gene Delivery
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.
September 12, 2013
Hyongsok (Tom) Soh, PhD
Ruth Garland Endowed Chair, Departments of Mechanical Engineering and Materials, University of California Santa Barbara
Cell Sorting and Directed Evoluation in Microfluidic Systems
Current techniques in high performance molecular and cellular separations are limited by the inherent coupling among three competing parameters: throughput, purity, and recovery of rare species. Our group utilizes unique advantages of microfluidics technology to decouple these competing parameters by precise and reproducible generation of separation forces that are not accessible in conventional, macroscopic systems. In this seminar, we will first discuss novel high performance electrokinetic, magnetophoretic and acoustophoretic separation systems to purify rare target cells from complex mixtures. Next, we will discuss our recent work in applying the microfluidic separation systems for Rapid Directed Evolution of molecules (RDE). We will provide theoretical and experimental evidence for extremely fast generation of affinity reagents -molecular recognition elements that bind to target molecules with high affinity and specificity. Finally, we will present innovative methods of evolving molecular machines that are capable of performing complex functions, including binding induced conformation change and switching.
October 10, 2013
Michael J. Cima, PhD
David H. Koch Professor of Engineering,
Faculty Director, Lemelson-MIT Program
Department of Materials Science and Engineering,
Massachusetts Institute of Technology
Microsystem Technologies for medical Applications
Medical technologies are evolving at a very rapid pace. Portable communications devices and other handheld electronics are influencing our expectations of future medical tools. The advanced medical technologies of our future will not necessarily be large expensive systems. They are just as likely to be small and disposable. These technologies are moving care from hospitals to outpatient settings, the physicians office, community health centers, nursing homes, and the patients home. Microsystems that are rapidly adopted fulfill significant medical needs and are compatible with existing clinical practice. This talk will review how Microsystems are already impacting health care as commercial products or in clinical development. I will emphasize applications that include diagnostics and local drug delivery. Two recent examples will be covered in more depth; NMR-based diagnostics, and device enabled drug delivery to the bladder.
November 14, 2013
Samir Iqbal, PhD
Associate Professor, Department of Electrical Engineering and Bioengineering (Courtesy),
Nanotechnology Research and Education Center,
University of Texas at Arlington
Nano-Textured and Tissue-Mimetic Environments for Cancer Diagnostics
Many types of surfaces and substrates have been functionalized for many years now, showing capture of biological entities at various size scales. Rare cells, however, require more than that. This talk shows the use of selective aptamers on nano-textured surfaces that mimic important parts of tissue structure. The malignant cells are captured, isolated and show unique physical and chemical signatures. Frame by frame analysis of the captured video provides quantifiable metrics for cell identification. The use of a simple anti-sense nucleic acid then releases the isolated cells for subsequent analysis. This approach opens up many new possibilities to interface living systems without disturbing their microenvironment. Early detection of rare cells (aka CTCs) with new interfaces and new recognition elements means much earlier diagnosis, better treatment and ultimately highly improved prognosis. Some potential applications of our work with aptamers and nanotechnology in isolation, sensing, interrogation, and interpretation of basic biologically important interactions will also be discussed.
December 6, 2013
Shiladitya Sengupta, PhD
Assistant Professor of Medicine and HST Director, Laboratory of Nanomedicine
Harvard Medical School Brigham and Women's Hospital
Challenging the Dogmas: Newer Insights in The Search For a Therapy for Cancer
The talk will focus on newer understanding of why chemotherapy fails and what are the early events in metastasis, and how chemotherapy can be rationally designed, especially from the global health disparity perspective. The speaker is the director of the Laboratory of Nanomedicine at the Brigham and Women's Hospital and Asst. Professor of Medicine and HST at Harvard Medical School. He is also the co-founder of Cerulean Pharmaceuticals.
December 12, 2013
Ian Baker, PhD
Sherman Fairchild Professor Engineering, Senior Associate Dean for Academic Affairs, Thayer School of Engineering,
Darthmouth Center for Cancer Nanotechnology Excellence
This talk outlines the Dartmouth Center of Cancer Nanotechnology Excellence (DCCNE), which focuses on the use of novel antibody-targeted magnetic particles (mNPs) subjected to an alternating magnetic field (AMF) for the treatment of tumors. The nanoparticles studied are either iron/iron oxide core/shell nanocomposite mNPs or iron oxide mNPs both with various organic coatings. There are four projects within the DCCNE. The first focuses on producing novel antibodies, determining their effect on tumor accumulation for a range of mNP sizes in mouse models and comparing the results to untargeted mNPs. The second project focuses on developing new imaging technologies to determine the binding, location, and concentration of the mNPs based on combining optical ratiometric fluorescence spectroscopy with magnetic spectroscopy of particle Brownian motion. The other two projects are therapy-focused on breast cancer, ovarian tumors and melanoma in mouse models. The breast cancer work involves direct injection of mNPs into a tumor. The synergistic effects of chemotherapy and radiation therapy with magnetic hyperthermia treatments have been examined. The ovarian cancer work involves development of strategies to determine the therapeutic effectiveness of introducing antibody-conjugated mNPs into the peritoneal cavity of ovarian cancer models. Both the ovarian cancer work and the melanoma effort are focused on developing an immune response. Some preliminary work on various oral tumors in dogs will also be outlined. The work has led not only to the development of treatment methodologies, but also to new nanoparticles, new nanoparticle measuring devices and new types of heating coils.
Sponsored by: Center for Cancer Nanotechnology Excellence and Translation - NIH/NCI U54 (MIPS);
Host: Director, Sanjiv Sam Gambhir, MD, PhD (email@example.com)
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