Cancer cells use two pathways to sense and move in tight quarters

COVER IMAGE CAPTION: Hung et al. describe two cooperating signaling modules by which cells sense and traverse confined spaces. Signaling output is optimized through complex feedback loops ultimately leading to efficient cell motility. Artist Jun Cen ( ) depicts a small diver exploring confined migration, which is symbolized by the large size and tangled arms of the octopus trying to squeeze into the cave.

Hung et al. describe cooperating signaling modules used by cells to sense and traverse confined spaces. Artist Jun Cen ( ) show a  small diver exploring confined migration symbolized by the tangled arms of the octopus trying to squeeze into the cave.

Like a bicycle messenger weaving through busy city streets, cancer cells are skilled at maneuvering through microenvironments. Researchers know they use complex signally pathways to move through and sense their surroundings, but exactly how these pathways worked was unclear.  Now, researchers from the Konstantinos Konstantopoulos laboratory at Johns Hopkins University have determined that both calcium and the cell protein myosin play a role in a cooperative feedback loop that makes cancer cells champions of  motility even in a tight squeeze  Their work appears in the May 17, 2016 journal Cell Reports, and an artist’s interpretation of the study graces the journal’s cover.

Wei-Chien Hung was the lead author on a study that used microfabricated growth chambers featuring narrow channels that the cells had to move through.  As the cancer cells migrated through the device, they had to squeeze and stretch to fit into confined spaces. As the cell membrane stretched, it caused special stretch-activated channels (called Piezo1 channels) to open. When the channels opened, calcium ions could flow through the cell membrane into the cell. The additional calcium ions set off a cascade of biochemical events leading to the activation of myosin.

As a molecular motor, myosin drove the cancer cells to move forward.  Myosin also served as a sensor that directly responded to external force and stretched the membrane.  This opened the channels, allowing more calcium ions to flow in; myosin in turn was further activated and so on.  This feedback system maximized the signaling output of the two sensors.

Screen Shot 2016-05-24 at 3.57.00 PMKonstantopoulos, professor and chair of Department of Chemical and Biomolecular Engineering and an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology, says that the two ways of sensing the environment and signaling movement in a microenvironment makes the motility of cancer cells extremely efficient and highly effective in confined spaces, such as what might be found inside of a tumor cell mass. These two pathways also present two potential targets on which cancer researchers can focus further investigation in order to prevent cancer cell migration.

Other authors on the paper include Jessica Yang, Christopher Yankaskas, Joy T. Yang and Jin Zhang. The research was funded in part by the NIH and the American Heart Association.

Written by Mary Spiro. For media inquiries regarding INBT, contact Mary Spiro at


The ethics of research supply purchasing in the life sciences

When people think about animal use and testing as it applies to research, especially in the life sciences, typically they imagine a scientist in a lab coat, running some experiment on a mouse or a rat. While this scenario is certainly a big part of animal involvement in life sciences research, another big part that often goes unnoticed or under-discussed is animal involvement in production of lab supplies.

For example, although some proteins can be non-invasively isolated or synthetically produced, many still have to be made in an animal and later isolated from them, commonly from serum, but quite possibly from other sources as well. Collagen, for instance, is a fibrous protein that makes up 25 to 35 percent of whole body content, and it can be used in many biological coatings because if its ability to crosslink and the fact that many cell types have a high affinity with collagen. When cultured on collagen, cells are more likely to stick.

In our lab, collagen is commonly used in the production of the microfluidic device that is being developed to mimic the properties of the blood-brain barrier. The collagen that we often purchase and use is rat-tail collagen, that is, collagen that has been isolated from the tendons found in the tails of rats. Other products include cell lines isolated from animals, and serums isolated from their blood.  Fetal bovine serum is also very commonly used in cell culture media, without which, cells would not survive in culture.

Another animal-derived lab product are antibodies. Antibodies are produced in animals by exposing them to a target protein. After the animal’s immune system recognizes the foreign protein, it produces antibodies against it, which can then be isolated and purified. Rabbits, goats, mice, rats, horses, and dogs are specifically bred for the production of antibodies.

Unfortunately not all antibody production facilities are kind to the animals they use. Recently, the USDA investigated Santa Cruz Biotechnology, one of the most prominent suppliers of antibodies for research purposes. SCBT has had 31 animal abuse violations filed against it in the past, but when the USDA sent a team to investigate in January 2016, thousands of rabbits and goats were gone, leading some to suspect that they may have been killed. (See story from Nature here.)

In many labs, antibodies are widely used. Decisions on where to buy antibodies are usually based on price and quality, because some antibodies will have higher affinities to the target proteins in question than the same antibody from another supplier. We don’t always consider ethics and company practices when we make our buying decision, but perhaps we should.

These days, since many alternate suppliers of antibodies exist it stands to reason to bring issues like animal treatment into the equation. This applies not just in the case of antibody purchasing, but in any situation where a supply is purchased for everyday lab use after having been produced by an animal. Unethical behavior that can exist behind the scenes in science and research will force researchers to do their due diligence when considering their sources for laboratory supplies. We do have a choice, and we can exercise it.

About the author: Luisa Russell is a fourth year PhD candidate in the Searson lab and also in the NTCR training program, whose research focuses on developing new strategies for cancer drug delivery using nanoparticles.

Media inquires should be directed to INBT’s science writer Mary Spiro,

Gerecht and Mao to join INBT leadership effective January 1

The Johns Hopkins Institute for NanoBioTechnology (INBT) recently announced that Sharon Gerecht and Hai-Quan Mao have been appointed as associate directors, effective January 1, 2016.

“The addition of Gerecht and Mao to the Institute’s leadership team will be crucial in developing new research areas,” says director Peter C. Searson, the Joseph R. and Lynn C. Reynolds Professor in Materials Science and Engineering at the Whiting School.


Hai-Quan Mao and Sharon Gerecht join INBT as associate directors in 2016

Associate director Denis Wirtz, Vice Provost for Research and the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering adds, “Their broad research interests and forward-thinking vision will contribute to shaping the institute’s future.”

Both Gerecht and Mao are engaged in collaborative projects with investigators in Johns Hopkins University’s School of Medicine, Bloomberg School of Public Health, and Krieger School of Arts and Sciences, and the university’s Applied Physics Laboratory.

Gerecht, the Kent Gordon Croft Investment Management Faculty Scholar and an associate professor of chemical and biomolecular engineering, has been a member of the INBT since arriving at Johns Hopkins in 2007. Gerecht’s research interests include stem cell differentiation, biomaterials development and tissue engineering approaches for regenerative medicine and cancer. In 2015, Gerecht received the inaugural President’s Frontier Award from Johns Hopkins University, in recognition of her scholarly achievements and exceptional promise.

Mao, a professor of materials science and engineering, has been active in INBT since its inception in 2006.  Mao holds joint appointments in the Translational Tissue Engineering Center in the School of Medicine and the Whitaker Biomedical Engineering Institute. His research focuses on creating nanofiber matrix platforms to direct stem cell expansion and differentiation, nanomaterials to modulate the immunoenvironment and promote neural regeneration, and developing nanoparticle systems to deliver plasmid DNA, siRNA, vaccines and other therapeutic agents.

“INBT has been instrumental in advancing science and engineering in critically important areas of research,” says Ed Schlesinger, the Benjamin T. Rome Dean of the Whiting School of Engineering. “An additional manifestation of the INBT’s success and growth is the astonishingly talented faculty who are part of the institute and who are willing and able to take on leadership roles. I have no doubt that in their new roles Sharon and Hai-Quan will help advance the INBT’s mission and its stellar reputation.”

INBT was launched in 2006 with support from Senator Barbara Mikulski to promote multidisciplinary research at the interface of nanotechnology and medicine.  The institute, with more than 250 affiliated faculty members from the Johns Hopkins University’s School of Medicine, Whiting School of Engineering, Krieger School of Arts and Sciences, School of Education, Bloomberg School of Public Heath, and the Applied Physics Laboratory, is home to several center grants and numerous education, training, and outreach programs.

All press inquiries about this program or about INBT in general should be directed to Mary Spiro, INBT’s science writer and media relations director at

New INBT symposium puts undergrad research in the spotlight

2015 INBT Undergraduate Symposium

2015 INBT Undergraduate Symposium

Johns Hopkins Institute for NanoBioTechnology (INBT) held its first-ever undergraduate research symposium “Innovations in Medicine: An Engineering and Biological Perspective” on Nov. 5, 2015 in the Glass Pavilion in Levering on the Homewood campus. Members of the INBT Undergraduate Research Leaders team organized the event.  Thirty-six posters were presented and four students gave keynote talks. Approximately 70 people attended throughout the day.

The symposium supports INBT’s mission to promote interdisciplinary research and collaboration at all academic levels. Since more than 100 undergraduates conduct research in institute-affiliated laboratories across the university, members of INBT’s Undergraduate Research Leaders, founded in 2012, felt a research symposium showcasing only undergraduate work was needed.

Ben Wheeler

Ben Wheeler

“We have in the past focused primarily on building community within INBT and helping to facilitate opportunities for undergraduates to build their research repertoire and network with others here at Hopkins and beyond,” said Benjamin Wheeler (2016 BME), who co-organized the event. “I think hosting the symposium fit very nicely with our previous goals and event planning experience but on a much larger scale. In organizing it, our goals were to allow undergraduates across all of Hopkins Campuses to showcase their amazing work while getting practice making posters, giving talks, and enjoying face time with professors and representatives from outside industry.”

In addition to poster presentations, four students were chosen to give talks during the symposium. They included: Andrew Tsai (BME 2017/Miller Lab) “Tunable Electrospun Antimicrobial Coatings for Orthopedic Implants;” Miguel Sobral (BME 2017/ Gerecht Lab) “Addressing the Shortcomings of Convection Enhances Delivery to the Brain;” Xinyi Xin (ChemBE 2017/ Cui Lab) “Tuning Paclitaxel-Drug Amphiphiles Self-Assembly Behavior by Modification of Hydrophobicity and Aromaticity;” and Michael Saunders (ChemBE 2016/ Gerecht Lab) “The Creation and Use of PDMS Substrates for Examining Matrix Elasticity.”

“We thought the symposium would be a great opportunity to feature the scientific research being done by undergraduate students at Hopkins not just within INBT but campus wide,” said event co-organizer Victoria Laney (ChemBE 2016). “We came up with ‘Innovations in Medicine’ as this year’s theme because we thought it really embodied the spirit of INBT and of many other labs at Hopkins.”

Victoria Laney

Victoria Laney

Prizes for top poster presenters were given to the following students:

First Place

  • Brendan Deng, “The Role of Megf11 in Oligodendrocyte Precursor Cell Tiling and Differentiation”

Second Place

  • Melissa Lin, “Monitoring Uterine Contractions in the Developing World”

Crowd Favorites

  • Fatima Umanzor, “Functional coupling of Cancer Cell Proliferation and Migration through the Synergistic Paracrine Signaling of Interleukins 6/8”
  • Asish Anam, “Design of a Novel Functionalized Hyaluronic Acid Hydrogel Microenvironment for Regulation of Cell Migration for Peripheral Nerve Regeneration Applications.”
2015 INBT Undergraduate Symposium

2015 INBT Undergraduate Symposium

The team invited judges to evaluate the posters on display. They included INBT alumni Matt Dallas (Thermo Fisher), Laura Dickson (Gemstone), and Steven Lu (Secant), current doctoral candidate Kristen Kozielski (Green Lab), and INBT affiliated faculty members Michael Edidin from biology and Jennifer Elisseeff from biomedical engineering.

Laney said the team intends to make sure the undergraduate symposium continues to happen for years to come.  “We absolutely plan on passing on the torch to our incredible juniors,” Laney said. “They also contributed a lot of time and effort into preparing this symposium, and we believe that they have the experience, dedication and enthusiasm to pull it off again.”


2015 Undergraduate Research Symposium

Story and photos by Mary Spiro.

All press inquiries about this program or about INBT in general should be directed to Mary Spiro, INBT’s science writer and media relations director at



A new wealth of applications for gold nanoparticles

Gold has been the currency of many civilizations because of its advantageous and attractive bulk properties. Many modern civilizations have left the gold standard, but the attractiveness of gold has not decreased. One reason is because of the development of gold nanoparticles.


Figure 1: Picture of gold nanoparticles embedded within Roman cup. When light is shown through the cup the gold nanoparticles reflect the red making it appear to change color. Source:

Although gold nanoparticles have been formed as early as the 4th century AD because of incorporation into cups such as shown in Figure 1, it has not been until the past 50 years that researchers have developed gold nanoparticle formation techniques and exceptionally characterized these particles enabling their usefulness.

Gold nanoparticles have found numerous applications both within and outside of biology. For example, the gold nanoparticles could be used as therapeutic delivery vehicles. Furthermore, specially shaped and sized nanorods can be exothermically excited by 700-800 nm light. This could be used to produce a hyperthermia treatment of tumors where the nanoparticles could be coated with a ligand for the tumor and then light shown only in the location of the tumor for site-specific therapy.

In addition, gold nanoparticles are commonly used in biological assays as detection agents for certain pathological conditions. Outside of biology, gold nanoparticles can serve as catalysts for chemical reactions and also be used in printable electronics. These and other currently investigated applications for gold nanoparticles provide a rich future for gold in our modern society.

About the author: John Hickey is a second year Biomedical Engineering PhD candidate in the Jon Schneck lab researching the use of different biomaterials for immunotherapies and microfluidics in identifying rare immune cells.

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


Thoughts on stereotyping of Latina women in science

Angela Jimenez

Angela Jimenez

Recently an article in the Washington Post entitled, “Black and Latina women scientists sometimes mistaken for janitors,” was brought to my attention. The Nano-Bio blog editor and INBT science writer, Mary Spiro, asked me if I would be willing to write a response to it. After considering this topic and my experience in the States, I cannot say that I have felt stereotyped due to being a female Hispanic scientist.

Although stereotyping is a more profound issue, it is not completely unreasonable. Let me explained myself: I recently defended my PhD work at Johns Hopkins University and in the five and a half years that I have spent here, most of the janitors are blacks including a few Hispanics. When I would walk to lab, I could hear construction guys talking in Spanish all the time. Unfortunately, this stereotype is sometimes our current reality. This could be partly explained from the fact that some of us come from developing countries, and it is difficult when we come to the States to be up to speed with everyone else who has been born and raised here. This gap could be due to a variety of factors, such as the lack of education, the cultural differences, the language barrier, and even the influence of our family.

One of the reasons that I have not felt particularly stereotyped is probably because when I moved to the States 13 years ago, I came to New York City, which is known as the melting pot of this country. I went to City College of New York and out of a class of 30, there was only one person originally from the States. Everyone else was from somewhere around the world.

After arriving to the US, I was aware that I was coming from a developing country, and that I needed to work hard to succeed, which I would define as getting educated. When I decided to come here, I moved without my family and without knowing any English and I feel that the most important thing that made me succeed was the great desire and determination to learn and get educated. This determination probably made me so focus on achieving my goals that I never really thought about being stereotyped or discriminated even when this could had been the case.

Looking back, I can only say that yes, I worked really hard, but I have been extremely fortunate to be able to earn a PhD from one of the leading Universities. Now, do I think it is fair that women, in particular Blacks and Hispanics, are stereotyped or even discriminated? Of course not, but the issue here is greater than this. Stereotyping and discrimination depend on several variables. For instance, geography, demographics, education, and income all play a role.

I have Hispanic Engineer friends who work in different industries in non-traditional roles, and I have observed that the ones who work in New York City are less likely to be stereotyped or discriminated than the ones elsewhere. Do I think that as women we should support each other and create societies that inspire and help us navigate the system? Of course yes! Motivating and helping women pursue a career in the field of science will help increase the percentage of women in these challenging positions. Over time, this will lead to a greater representation of the number of blacks and Latina women scientists, and this current stereotype and discrimination will eventually vanish.

About the author: Angela Jimenez recently completed her PhD in Chemical and Biomolecular engineering in the laboratory of Denis Wirtz, associate director of INBT and Vice Provost for Research at Johns Hopkins University.

New eyes for diagnostics

Initial medical diagnoses are done based on physical examination by a health care professional. However, as the technology of optics, computing, and biology continues to advance, engineers have essentially developed “enhanced eyes” for health care professionals to see beyond the limits of our natural vision to diagnose patients. For example, with the advent of ultrasound, doctors are able to see into a pregnant mother’s womb to monitor the health of a developing baby.

Figure 1: How imaging modalities are being combined to more precisely diagnose patients. In this image high levels of cell activity are being identified to pinpoint cancer existence. Source:

Figure 1: How imaging modalities are being combined to more precisely diagnose patients. In this image high levels of cell activity are being identified to pinpoint cancer existence. Source:

New imaging techniques and machines are combining existing modalities. This improves diagnoses and combines the strengths of each imaging modality. For example, cancer diagnosis can now be achieved by scanning a patient with a dual PET/CT machine (Fig. 1). In this method, imaging specialists combine the strength of CT scans, which shows high resolution of organ location and tissue distribution, and PET scans, which determines molecular/cellular activity by introducing a radioactive molecule into the body.

These technologies have also increased our understanding of diseases and are used frequently in research to develop new theories for disease mechanisms. Nevertheless, because of the amount of technology and engineering that has gone into developing these machines, they are still very costly both to patients and researchers.

About the author: John Hickey is a second year Biomedical Engineering PhD candidate in the Jon Schneck lab researching the use of different biomaterials for immunotherapies and microfluidics in identifying rare immune cells.

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

Nanodevices built with DNA origami

Did you know DNA could be used for origami?

Not actual DNA origami.

Not actual DNA origami.

The precise control and organization of nanoscale devices has shown a great potential for ultimately creating “nano-devices” that can perform nanoscale biological measurements, deliver medicine in vivo, among many other applications. A recent article from Carlos E. Castro and colleauges from The Ohio State University demonstrates the use of DNA origami with programmable complex and reversible 1D, 2D and 3D motions.

By varying the DNA origami design, they were able to observe different mechanisms for the DNA origami’s 3D motion such as the crank-slider and four bar mechanism. The research team mainly utilized transmission electron microscopy (TEM) to follow the morphology changes as the origami moves.

DNAUsing a fluorescence quenching assay (attaching a fluorescent label on one arm and a quencher on the other), they have characterized the timescale of DNA origami motion. Overall, their group sees this technology as a “foundation for developing and characterizing a library of tunable DNA origami kinematic joints and using them in more complex controllable mechanisms similar to macroscopic machines, such as manipulators to control chemical reactions, transport biomolecules, or assemble nanoscale components in real time.”


Shown below are some of the videos showing the motions of the DNA origami that they have reported:

About the author: Herdeline Ann M. Ardoña is a third year graduate student at Johns Hopkins University Department of Chemistry, currently working in chemistry professor J.D. Tovar’s lab and co-advised by professor Hai-Quan Mao, in materials science and engineering.

Reference: Programmable motion of DNA origami mechanisms. (Proc. Natl. Acad. Sci. U.S.A., 2015, 112, 713-718)

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

Are there problems with the peer-review process?

The pathway to publication is littered with checkpoints, reviews, and rejections. Before your paper is accepted it is read and reviewed with a few possible fates. It can be desk rejected by the editor and never reviewed or it can reach the reviewers who then decide the fate of the manuscript.

questionamarkwebSiler et al. investigated the effectiveness of the review process. They observed that top ranking journals overall have a very effective desk screening process where the best manuscripts are selected for review. However, there was one main fault; these top tier journals desk rejected the top cited manuscripts. This is likely due to the fact that their goal is to publish papers that are widely applicable and of interest to many people. This limits the ability of truly novel and exciting works to be published in these formats.

Overall, however, it was determined that the review process is helpful. Manuscripts that went to review overall had more citations than those desk rejected and resubmitted elsewhere. The results of this study were reassuring, and it was nice to see that at least a few scientists are looking into the effectiveness of the review process.

Link to article:

About the author: Moriah Knight is a third year in the Johns Hopkins Department of Materials Science and Engineering working in Peter Searson’s lab.

Nano-bio lab course: MAPs and CD

Editor’s note: Over the next several days, we will share the student impressions of some of the techniques learned in INBT’s nano-bio laboratory course (670.621). These reports demonstrate the wide variety of techniques students trained at the Johns Hopkins Institute for NanoBioTechnology are expected to understand. Each technique is taught in a different affiliated faculty lab. More lab techniques to come.

Membrane Active Proteins (MAPs) and Circular Dichroism (CD) spectrography

During this lab, we learned a couple of techniques that I had not used before. First we synthesized liposomes and processed them, resulting in uniform liposome radius. Then we made a solution of membrane active proteins with aromatic amino acids so that their absorbance and emission could be measured.


circular dichroism (CD) spectrography

We ran the proteins through the fluorometer at varying wavelengths to create a profile of emission and absorbance of the protein. This was done also at varying pHs and at different liposome concentrations.

In theory the proteins should incorporate into the liposomes and there should be a change in the spectra as a result. During our lab time we had issues getting the desired results, but it was still informative on how to use the fluorometer and other new equipment. We found the spectra for two different proteins at two different pH values for each to see the effect that pH had on the emission/absorbance spectra.

We also preformed CD spectrography (circular dichroism) to determine the chirality of the proteins, that is, how are the specific molecules spatially arranged. Again the procedure did not work exactly as planned, but learning how to perform the measurement was informative, nonetheless.

About the author: Jackson DeStefano is a first year PhD candidate in the laboratory of Peter Searson, professor of materials science and engineering.

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