Podcast: Artificial blood vessel visualizes cancer cell journey

Researchers from Johns Hopkins Institute for NanoBioTechnology are visualizing many of the steps involved in how cancer cells break free from tumors and travel through the blood stream, potentially on their way to distant organs.  Using an artificial blood vessel developed in the laboratory of Peter Searson, INBT director and professor of materials science and engineering, scientists are looking more closely into the complex journey of the cancer cell.

Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue).

Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue). (Wong/Searson Lab)

INBT’s science writer, Mary Spiro, interviewed device developer Andrew Wong, a doctoral student Searson’s  lab, for the NanoByte Podcast. Wong is an INBT training grant student. Listen to NANOBYTE #101 at this link.

Wong describes the transparent device, which is made up of a cylindrical channel lined with human endothelial cells and housed within a gel made of collagen, the body’s structural protein that supports living tissues. A small clump of metastatic breast cancer cells is seeded in the gel near the vessel while a nutrient rich fluid was pumped through the channel to simulate blood flow. By adding fluorescent tags the breast cancer cells, the researchers were able to track the cells’ paths over multiple days under a microscope.

VIDEO: Watch how a cancer cell approaches the artificial blood vessel, balls up and then forces its way through the endothelial cells and into the streaming fluids within the channel of the device. (Video by Searson Lab)

The lab-made device allows researchers to visualize how “a single cancer cell degrades the matrix and creates a tunnel that allows it to travel to the vessel wall,” says Wong. “The cell then balls up, and after a few days, exerts a force that disrupts the endothelial cells. It is then swept away by the flow. “

Wong said his next goal will be to use the artificial blood vessel to investigate different cancer treatment strategies, such as chemotherapeutic drugs, to find ways to improve the targeting of drug-resistant tumors.

Results of their experiments with this device were published in the journal Cancer Research in September.

Andrew Wong (left) and Peter Searson. (Photo by Will Kirk/Homewood Photography)

Andrew Wong (left) and Peter Searson. (Photo by Will Kirk/Homewood Photography)

Check out this gallery of images from the Searson Lab. The captions are as follows:
Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue).
Figure 2. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a vessel with dual-labeled MDA-MB-231 breast cancer cells on the periphery.
Figure 3. Phase-contrast and fluorescence overlays depicting a functional vessel comprised of human umbilical vein endothelial cells (HUVECs) with dual-labeled MDA-MB-231 breast cancer cells on the periphery (green in the nucleus, red in the cytoplasm).

 

 

Don’t believe everything (peer-reviewed) you read on the web

Recently, my attention was drawn to an article the same way I find many articles: through Facebook. Several of my many science-minded friends referenced a recent article from sciencemag.org entitled “Who’s Afraid of Peer Review?”, where a spoof paper with clearly bad controls was submitted to 304 open access journals and was accepted by 157. After reading a variety of comments with tones ranging from outrage to, “damn, I need to start writing some fake papers,” there was no way I wasn’t going to check out the article.

peer review image

Image used with permission from http://strange-matter.net/screen_res/nz060.jpg

Basically, some writers from Science generated a fake paper the claimed a chemical extracted from a lichen had shown anticancer properties. While the article claimed that there was a strong dose-dependent effect of the drug on the cancer cells, the effect barely varied over 5 orders of magnitude. The paper claimed that the chemical was dissolved in large amounts of ethanol before being added to cells, but the control cells were given no ethanol, meaning that likely what was killing the cells was not in fact the chemical, but the ethanol itself. Testing controls with the same solvent as the other conditions is standard, especially when large amounts of the solvent itself can have toxic effects. The spoof paper also went on to make large claims about how the molecule tested has potential as an anticancer drug.

It would seem likely, given the inherent flaws in the article, that the academics reviewing this paper would immediately raise a red flag about its content. However, the majority of the journals accepted the paper, including 45% of the journals in the Directory of Open Access Journals (DOAJ), which is meant to identify the credible open access journals. Many of the journals that offered the authors any feedback ignored the glaring scientific mistakes and simply made suggestions for changes in formatting.

As a grad student, I read peer-reviewed papers nearly every day. And while I’ve always known that I should be critical of everything I read, I was still shocked that this spoof article with such glaringly bad science was accepted by so many publishers. While I’m not as tempted to submit my own fake articles as some of my Facebook friends, this sting operation performed by the writers at Science is making me much more skeptical of papers I find on the web.

Amanda Levy is a doctoral student in the materials science and engineering laboratory of Peter Searson, director of INBT.

 

REU student profile: Christopher Glover

Christopher Glover is a rising senior in bioengineering at the University of Missouri. He worked this summer as an REU intern in the laboratory of professor Jeff Tza-Huei Wang, who has joint appointments in mechanical engineering, biomedical engineering and oncology. The Research Experience for Undergraduates, hosted by Johns Hopkins Institute for NanoBioTechnology, attracts nearly 800 undergraduate applicants for just 10 research positions.

Christopher Glover

Christopher Glover

Christopher’s project involved a proof-of-concept experiment to test a device used to digitally sort and amplify DNA samples.

The device consists of a silicone chip imprinted with 3,000 tiny wells to contain DNA. A thermoplastic lid covers the top of the chip to keep the DNA in place in the wells. After a segment of DNA is added to the chip, the number of copies of that DNA segment is amplified using a device called a thermal cycler. “The goal is to either get zero or one copy of the DNA segment in each well, which makes the device “digital,” he said.

“We aren’t concerned about the type of DNA we are amplifying but just to see if it will work,” Christopher said. “This could be used for medical screening where a specific allele could be detected within a gene to see if someone is more susceptible to getting a disease,” he said.

Christopher said that working in the Wang lab has helped him learn much more about nanotechnology than he had previously known. His future plans include earning a PhD in biomedical engineering.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

REU student Profile: Florencia Velez-Cortes

Florencia Velez-Cortes is a rising senior in physics and chemistry at The Ohio State University. As part of INBT’s REU program, she spent her summer as a research intern the chemical and biomolecular engineering laboratory of professor David Gracias. REU stands for Research Experience for Undergraduates and is a National Science Foundation program hosted by the Johns Hopkins Institute for NanoBioTechnology.

Florencia Velez-Cortes

Florencia Velez-Cortes

Florencia worked constructing bi-layers out of DNA and acrylamide gel. The combination of the two materials could be used the make biocompatible devices, such as microgrippers that could be used in tether-less surgery, she explained.

“The best part about this project is that we are working on something complete new and biocompatible that could even be responsive to chemical signals,” she explained.

Also because the material is composed of DNA, “it could be responsive to certain DNA sequences.”

Florencia said the most challenging thing for her this summer was working with people who are engineers, when she is not. “It’s been a steep learning curve for me but everyone has been really helpful and receptive to working with someone who is outside of their field.”

She also noted that the pace of research in the Gracias lab is a lot faster than what she is used to in her previous laboratory experiences. She said having a mentor she could talk to was integral to her success.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

Nanobio film festival projects posted to YouTube

Each summer, I teach a course through Johns Hopkins Institute for NanoBioTechnology for our training grant students in science communication. The course, Science Communication for Scientists and Engineers: Video News Release (EN.670.609), teaches students methods for communicating their research to a nontechnical audience. Topics covered include conveying your research in 60 seconds, scripting, story boarding and video camera filming and techniques.

inbt-abstractMartin Rietveld, INBT’s web and animation director, and the staff at the Digital Media Center on the Homewood campus, also play an integral part in this short summer workshop. The class meets four times for lecture and discussion, where they are shown many science videos and discuss case studies on what works in communicating technical information to a lay audience. They visit the DMC and INBT’s animation studio. The student groups then have approximately five weeks to work independently on their projects. At the end of the course, students show their completed videos at the INBT film festival.

This year the film festival was held on July 23 with nearly 50 people in attendance. We had 12 filmmakers split into three groups of four students.  The topics and teams and resulting videos follow. Enjoy!

Cancer

Ivie Aifuwa, chemical and biomolecular engineering, Denis Wirtz Lab

Moriah Knight, materials science, Peter Searson Lab

Christopher Saeui, biomedical engineering, Kevin Yarema Lab

Zinnia Xu, biomedical engineering, Peter Searson Lab

Lab-on-a-Chip Technology

Prasenjit Bose, physics, Daniel Reich Lab

Sarah Friedrich, biomedical engineering, Jeff Wang Lab

Erin Gallagher, materials science and engineering, Peter Searson Lab

Yu Shi, physics, Daniel Reich Lab

In Vitro Models for Testing Drug Delivery

Max Bogorad, materials science and engineering, Peter Searson Lab

Alex Komin. materials science and engineering, Peter Searson Lab

Luisa Russell, materials science and engineering, Peter Searson Lab

Bin Sheng Wong, chemical and biomolecular engineering, Konstantinos Konstantopoulos Lab

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

 

 

 

REU student profile: Rebecca Majewski

DNA, the genetic sequence that tells cells what proteins to manufacture, typically resides inside the nucleus of a cell, but not always. Rebecca Majewski is studying the uptake of DNA into cell nuclei using a different polymer chains. Rebecca is a rising senior in BioMolecular Engineering from the Milwaukee School of Engineering and is working as a summer intern in the Johns Hopkins Institute for Nanobiotechnology’s REU program.

“We are interested in how much of the DNA with the polyplex can get into the nucleus,” she said, but explains that DNA associated outside of the nucleus can cause false higher measurements.

Rebecca Majewski. Photo by Mary Spiro

Rebecca Majewski. Photo by Mary Spiro

Rebecca is washing the cells with the nuclei to get rid of DNA outside the nucleus and then comparing the measurement of uptake of the DNA by the cell versus the measurement of the uptake of DNA by the nucleus.

“We are interested in what DNA gets inserted into the nucleus because that is what is ultimately expressed. It is important to find out how much makes it to the final destination and then is expressed. The goal of this work is to test different polymer chains to see which one actually does the better job of getting the DNA into the nucleus,” she said.

Rebecca works alongside PhD students and postdoctoral fellows in the biomedical engineering lab of Jordan Green lab at the Johns Hopkins School of Medicine. She says she highly values the opportunity for a research experience through INBT’s REU because her undergraduate institution does not train graduate students.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

Three new science and engineering films to premiere at INBT fest

INBT’s Annual SCIENCE and ENGINEERING Film Fest is Wednesday, July 23 at 10:30 a.m. in Schaffer 3 at Johns Hopkins University Homewood campus. Students from the summer class Science Communication for Scientists and Engineers: Video News Releases will be presenting their final projects and be availablmovie_clapper_board_clip_art_23354e for question and answer about their video news releases.

Film topics this year include drug delivery, lab-on-a-chip technology and how cells become cancerous. Don’t miss this opportunity to see the students’ work up on the big screen!!!!!!! This event is open to the entire Johns Hopkins community. FREE.

Facebook event page here.

Check out a previous video made in this class:

REU student profile: Ian Reucroft

Sitting at what looks like a pottery wheeled turned on its side, Ian Reucroft is using a method called electrospinning to create a nano-scale polymer fiber embedded with a drug that encourages nerve growth. The strand is barely visible to the eye, but the resulting fibers resemble spider web.

Ian Reucroft, a rising junior in Biomedical Engineering at Rutgers University, is working in the medical school campus laboratory of Hai-Quan Mao, professor of materials sciences and engineering at Johns Hopkins University. He is part of Johns Hopkins Institute for NanoBioTechnology’s summer REU, or research experience for undergraduates program.

Ian Reucroft in the Mao lab. Photo by Mary Spiro.

Ian Reucroft in the Mao lab. Photo by Mary Spiro.

“We are developing a material to help regrow nerves, either in central or peripheral nervous systems,” said Ian. One method of doing that he explained is to make nanofibers and incorporating a drug into those fibers, drugs that promote neuronic growth or cell survival or various other beneficial qualities. The Mao lab is looking into a relatively new and not well-studied drug called Sunitinib that promotes neuronal survival.

“We make a solution of the component to make the fiber, which is this case is polylactic acid (PLA), and the drug, which I have to dissolve into the solution,” Ian said. Although the drug seems to remain stable in solution, one of the challenges Ian has faced has been improving the distribution of the drug along the fiber.

This is Ian’s first experience with electrospinning but not his first time conducting research. He plans to pursue a PhD in biomedical engineering and remain in academia.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

The IMEC blog and why you should read it

Every summer since 2009, Johns Hopkins Institute for NanoBioTechnology has been sending students to the lovely town of Leuven in Belgium to conduct 10 weeks of research at IMEC, that country’s leader in nanoelectronics fabrication and testing. The students, both undergraduates and pre-doctoral students, collaborate on projects coordinated by Hopkins and IMEC faculty.

The research program is co-funded by the National Science Foundation International Research Experience for Students (IRES) program, by INBT and by IMEC. Travel, housing and a stipend are covered for each student. They work hard during the week, but weekends are open for European travel, which they all take advantage of.

IMEC summer researchers from left, Matthew Gonzalez, Polly Ma, Rustin Golnabi and Eugene Yoon.

IMEC summer researchers from left, Matthew Gonzalez, Polly Ma, Rustin Golnabi and Eugene Yoon.

We ask the students to blog about their experiences there. Four students are currently working at IMEC for summer 2014. This year the blog has been pretty active, so we invite you to check it out. Find out what it is like to conduct research in a foreign country. Find out about Belgian beer. Experience their summer away vicariously through their writings and photos.

You can find the IMEC blog here.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

Congratulations to INBT symposium poster prize winners

Five winners took home prizes during the poster session held at the annual symposium hosted by Johns Hopkins Institute for Nanobiotechnology May 2 at the School of Medicine. The theme of the symposium was Stem Cell Science and Engineeering: State of the Art. Fifty-six posters were presented from disciplines across the university and were judged by faculty and industry experts. First, second and third place winners won Nikon cameras and honorable mentions won digital frame key chains.

DSC_0186

From left, Rebecca Schulman, Thomas Joseph, Kirsten Crapnell, Lauren Woodard, Jane Chisholm, Tao Yu, and Robert Ivkov. (Photo by Yi-An Lin)

The winners and poster titles included:

First Place:

Lauren Woodard: Synthesis and characterization of multifunctional core-shell magnetic nanoparticles for cancer theranostics. Lauren E. Woodard, Cindi L. Dennis, Anilchandra Attaluri, Julie A. Borchers, Mohammad Hedayati, Charlene Dawidczyk, Esteban Velarde, Haoming Zhou, Theodore L. DeWeese, John W. Wong, Peter C. Searson, Martin G. Pomper* and Robert Ivkov.

Second Place:

Tao Yu:  Intravaginal Delivery Of Paclitaxel Via Mucus-Penetrating Particles For Local Chemotherapy Against Cervical Cancer. Yu T, Yang M, Wang Y-Y, Lai SK, Zeng Q, Miao B, Tang BC, Simons BW, Ensign L, Liu G, Chan KWY, Juang C-Y, Mert O, Wood J, Fu J, McMahon MT, Wu T-C, Hung C-F, Hanes J.

Third Place:

Jane Chisholm: Mucus-penetrating cisplatin nanoparticles for the local treatment of lung cancer. Jane Chisholm, Jung Soo Suk, Craig Peacock, Justin Hanes.

Honorable mentions went to:

Anilchandra Attalur: Magnetic Nanoparticle Hyperthermia As Radiosensitizer For Locally Advanced Pancreas Cancer. Anilchandra Attaluri, Haoming Zhou, Yi Zhong, Toni-rose Guiriba, Mohammad Hedayati, Theodore L. DeWeese, Eleni Liapi, Christine Iacobuzio-Donahue, Joseph Herman, and Robert Ivkov

Maureen Wanjare:  The Differentiation and Maturation of Vascular Smooth Muscle Cells Derived from Human Pluripotent Stem Cells using Biomolecular and Biomechanical Approaches. Maureen Wanjare, Frederick Kuo, Gyul Jung, Nayan Agarwal, Sharon Gerecht

Poster Judges included Robert Ivkov, PhD, assistant professor in radiaton oncology/ radiobiology and Seulki Lee, PhD, assistant professor in neuroradialogy, both from the Johns Hopkins School of Medicine; Rebecca Schulman, PhD, assistant professor in chemical and biomolecular engineering at the Whiting School of Engineering; and Kirsten Crapnell, PhD, and Thomas Joseph, PhD, both of BD Diagnostics.

Check out a gallery of some photos from the poster session shot by PhD candidate Yi-An Lin who works in the laboratory of Honggang Cui in the Department of Chemical and Biomolecular Engineering.