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Posted: Jun 02, 2011

Cancer Nanotechnology: an overview of INBT's 2011 symposium talks

(Nanowerk News) Seven speakers presented at Johns Hopkins Institute for NanoBioTechnology's fifth annual nano-bio symposium, held May 13, 2011 at Shriver Hall on the Homewood campus. This year's topic – cancer nanotechnology – was approached from a variety of angles. Approximately 300 people attended the talks and the poseter session that followed in the afternoon.
INBT hosts its symposium each year on a topic related to nanobiotechnology for the more than 200 affiliate faculty members and their students, postdoctoral fellows and staff. Government and industrial scientists and engineers are also invited to attend the event. The symposium has served as a platform for discussion on nanobiotechnology topics such as nanoparticles in the environment, policy, neuroscience and neurosurgery and nanotechnology for cancer medicine.
Here are brief summaries of what each speaker had to share during the 2011 event. Summaries were written by volunteer INBT affiliated students and staff. Authors are indicated in parentheses at the end of each summary.
"Why develop sensitive detection systems for abnormal DNA methylation in cancer?" ~ Stephen B. Baylin, professor, Johns Hopkins School of Medicine

Stephen Baylin
"There is tremendous need for early detection of cancer… a need to find circulating tumor cells in the blood," Baylin said, and creative nanotechnology science may be the tool that allows for this early detection. Baylin, who is involved in a group of researchers using epigenetics for cancer strategies, compared DNA to a computer's hard drive, while the epigenome would be more like a computer's software, he said, giving instructions on how and when to use that genetic information. DNA methylation, in which a chemical group is added to the backbone of the code's double helix, is a cancer specific biomarker that can be identified with nanotechnology based tools. "Detecting these molecules and knowing their biology and their methylation offers us another hope," Baylin said, "because we have drugs now that can change a methylated DNA back to its non-methylated state." Furthermore, Baylin noted that different types of colon cancers, for example, methylate differently. "This can tell you not only the stage but where the cancer is located in the gastro-intestinal tract," he said. Baylin referenced the work of Johns Hopkins colleagues and INBT affiliated faculty members Luis Dias at the School of Medicine and Jeff Wang in the Whiting School of Engineering, who use nanotechnology based methods to detect cancer biomarkers in cells found in bodily fluids. Baylin said highly sensitive methylation detection techniques like these will improve patient outcomes by finding cancer-causing cells in their precursor stages. Sensitive methylation detectors may also enhance efforts to personalize medicine by identifying subsets of patients who respond well to certain types of drugs. (Mary Spiro)

"Enabling cancer drug delivery using nanoparticles" ~ Anirban Maitra, professor, Johns Hopkins School of Medicine

Nanoparticle driven cancer treatment is a popular, and obviously important topic in cancer nanotechnology. Maitra touched on a couple of the strategies his team has developed. Through a mechanism known as desmoplasia, efficacy of Placitaxel was greatly improved with Maitra's albumin functionalized nanoparticles. Desmoplasia is the process of "stromal depletion" Maitra said and it was recently found to be an active process that can be initiated through binding of albumin to SPARC, a receptor commonly found on pancreatic stromal cells. The stromal breakdown allows for much greater nanoparticle transport to cancer cells "by removing the physical barrier" the stroma presents, said Maitra. Maitra also discussed another part of his work involving inhibition of the hedgehog pathway to suppress basal cell carcinoma. Maitra showed an image of a patient from a clinical trial with lesions all over the body and after treatment with hedgehog inhibitor GDC449, the lesions all vanished. However, this same patient and many others from the study relapsed due to what Maitra believed to be a "secondary mutation." Maitra hopes to now find a way to bypass this "evolutionary response" and permanently remove these cancerous lesions. Maitra's research includes a host of nanoparticle based approaches personalized for different types of cancer with hopes that specificity will eliminate unnecessary side effects and improve treatment overall. (Gregg Duncan)

"Epithelial Morphogenesis in Cancer Metastasis" ~ Gregory Longmore, professor, Washington University in St. Louis School of Medicine

Greg Longmore highlighted the sad reality about cancer: it's rarely the primary tumor that kills someone, but 90 percent of the time it's the metastatic spread. Thus, his research has sought to understand how tumors evade tissue and the genetic cues the invasive cells give one another to invade the epithelium, which is the barrier that lines glands and surface structures of the body. "Understanding this process is critical to maintaining tumor dormancy and for treating metastatic disease," he said. His laboratory has also focused on development and the similarities between normal tissue growth and the spread of cancerous cells throughout the body. (Jacob Koskimaki)

"Nanoparticle Based Imaging Method For Cancer" ~ Martin Pomper, professor, Johns Hopkins School of Medicine

Once objects are shrunk to sizes comparable to the wavelength of light, interesting optical phenomena can be observed and Pomper has been exploiting this with nanoparticles and molecules for high resolution imaging for cancer. Molecular imaging with "picomolar sensitivity," Pomper said, would be ideal for early detection of cancer where small numbers of cancerous cells are present, or even down to imaging genes. A cationic nanoparticle functionalized with a gene able to identify the PEG-Prom gene, which has been shown to be upregulated in cancer cells, was developed to allow for cancer cell specific imaging. This could allow for physicians to tell the difference between inflammation and early tumor formation. Pomper mentioned that one reviewer of a paper he submitted wanted to know how his imaging techniques compared to the current medical standard. It was clearly seen from images of a patient with breast cancer, only the cancerous areas were highlighted with Pomper's nanoparticle-based imaging while the whole breast was tagged with a standard SPECT image. Pomper also discussed a new therapeutic agent his group had been researching the [131I] FIAU "hand grenade." This radioactive isotope is a beta-particle emitter that could be initiated at the site of a tumor that could drastically reduce the negative side effects with typical radiotherapies. Pomper's work has shown how moving down to the nano-regime for imaging could greatly increase diagnostic capabilities for cancer where early and accurate detection is key. (Gregg Duncan)

"Cancer Cell Motility in 3D" ~ Denis Wirtz, professor, Johns Hopkins Whiting School of Engineering

Denis Wirtz jokingly apologized for not having cells to show in 3D “like Pixar,” but he had a strong message about the importance of understanding how cells move and the ways his lab is facing the challenge of studying cell motion in three dimensions. Metastasis is the relocation of malignant cancer cells from the original tumor to another part of the body where they take root and cause more disease, and it is often the aspect of cancer that is most deadly. To understand metastasis, scientists probe underlying functions: how cells attach to the surfaces of other cells or the extracellular matrix, how cells are cued to migrate, how they accomplish a movement. Most commonly, scientists study cell motion on two-dimensional surfaces. This makes experiment design and imaging the cells fairly straightforward, but it is not very realistic for most types of cells. “Cells encounter an intrinsically 3D space” in the tissues of the body, said Wirtz, and his lab has taken on the challenge of experimentally simulating that. Using new techniques to observe cells moving within a material and upon a surface, researchers in the Wirtz Lab have found that features that are present in 2D situations, such as clear attachment points between the cells and the surface, don’t have obvious analogues in the 3D situation. They found, however, that cells move by sending out protrusions of their membranes through the material, and how fast they could move depends on how much the protrusions branch. To accomplish this research, the researchers in the Wirtz Lab refined a technique called reflection confocal microscopy and were able to analyze cell motion by tracking how the cell deformed the material around them. This research can help us understand how malignant and highly mobile cells move through the tissues of the body. (Dan Richman)

"MRI as a Tool For Developing Vaccine Adjuvants" ~ Hy Levitsky, professor, Johns Hopkins School of Medicine

We know from experience with certain infectious disease vaccines that vaccination is a way to get the body to improve its own ability to fight disease. Vaccines can also be used to fight cancer by conditioning the immune system to recognize tumor cells as disease cells and target them for destruction. In Hy Levitsky’s lab, researchers are increasing the efficacy of tumor vaccine by carefully tracking how well the vaccine gets to the right immune cells in the body. In order to start targeting tumors, immune cells have to “learn” about the tumor cells by being presented with a marker for the cell called an antigen. Therefore, the vaccine that is injected into the body contains parts of tumor cells. In addition, the vaccine contains what are called adjuvants, which are substances that enhance the delivery of the antigen to the immune system. In order to track how different adjuvants affect the delivery of the antigen, Levitsky’s lab includes a chemical label in the vaccine that shows up in magnetic resonance imaging (MRI). Since the label, adjuvant, and antigen are absorbed together by cells in the body, imaging the location of the label allows the delivery of the antigen to be monitored. The Levitsky Lab used the technique to show that using a certain adjuvant along with a tumor cell antigen increased the number of immune cells in mice that picked up the antigen and moved to a lymph node to present it to other immune cells that would target a tumor. This research evaluated the effectiveness of a particular adjuvant to improve vaccine delivery and also demonstrated a new technique to track vaccine delivery in general. (Dan Richman)

"Genetically-Encoded Fret-Based Biosensors For Probing Signaling Dynamics" ~ Jin Zhang, associate professor, Johns Hopkins School of Medicine

How do cells sense the environment and make a response if needed? The question has driven Jin Zhang's research. "Cells use very smart strategies to regulate signaling," she said. For instance, calcium is an important signaling molecule that drives insulin secretion, but its activity is regulated by another molecule called PKA (protein kinase A). Exactly how these two molecules coordinate a response to finely-tune insulin secretion has eluded researchers. Her laboratory has used a fluorescent probe to track the response of PKA to generate a model of calcium and the PKA response, including spatial and time-inclusive data. She hopes her research will create more targeted treatments to help regulate this process in cells. (Jacob Koskimaki)

About the writers:

Gregg Duncan is a pre-doctoral fellow in Chemical and Molecular Biology conducting research in the >Michael Bevan Lab at the Whiting School of Engineering.

Jacob Koskimaki is a pre-doctoral fellow in Biomedical Engineering conducting research in the Aleksander Popel Systems Biology Lab at the Johns Hopkins School of Medicine.

Dan Richman is a pre-doctoral fellow in Physics conducting research in the Blake Hill Lab, Department of Biology, Krieger School of Arts and Sciences

All three are Integrative Graduate Education and Research Trainees (IGERT) supported by INBT and the National Science Foundation.

Mary Spiro is INBT's Science Writer

Source: Johns Hopkins Institute for NanoBioTechnology
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