Drug-chemo combo destroys challenging breast cancer stem cells

Gregg Semenza

Gregg Semenza

Researchers affiliated with Johns Hopkins Physical Sciences-Oncology Center (PS-OC) have shown that combining chemotherapy with an agent that blocks a certain cancer survival protein holds the key to fighting one of the the toughest forms of breast cancer.

Only 20 percent of patients with what are known as “triple-negative” breast cancer cells respond to chemotherapy. PS-OC associate director and Johns Hopkins professor of  medicine Gregg Semenza demonstrated in a recent study that chemotherapy actually enhances triple-negative cancer stem cell survival by switching on proteins called hypoxia-inducible factors (HIF). But when combined with currently available and FDA-approved HIF-inhibiting drugs, such as digoxin, Semenza said, chemotherapy shrank tumors.

Mice with implanted triple-negative breast cancer stem cells were treated with a combination therapy comprised of the HIF-inhibiting drug plus the chemotherapeutic drug paclitaxel. That combo treatment decreased tumor size by 30 percent more than treatment with chemotherapy. Furthermore, Semenza’s study showed that combining digoxin with the a different chemotherapeutic agent called gemcitabine “brought tumor volumes to zero within three weeks and prevented the immediate relapse at the end of treatment that was seen in mice treated with gemcitabine alone,” a press release on the study stated. Clinical trials will be needed to verify these results.

Debangshu Samanta, Ph.D., a postdoctoral fellow in the Semenza lab, was the lead author on this research published online in the Proceedings of the National Academy of Sciences. Additional authors include Daniele Gilkes, Pallavi Chaturvedi and Lisha Xiang of the Johns Hopkins University School of Medicine.

Read the PNAS article here.

Visit the PS-OC website here.

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

 

Gerecht nets American Heart Association grant

Sharon Gerecht, associate professor in the Department of Chemical and Biomolecular Engineering and affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology, has received the prestigious American Heart Association Established Investigator Award.

sharongerecht_cropThe AHA awarded only four such grants this year, funding designed to support mid-career of investigators who show unusual promise and accomplishments in the study of “cardiovascular or cerebrovascular science.”

Gerecht’s research focuses on engineering platforms, specifically hydrogels, that are designed to coax stem cells to develop into the building blocks of blood vessels. The hope is that these approaches could be used to help repair circulatory systems that have been damaged by heart disease, diabetes, and other illnesses.

Additionally, Gerecht leads a research project in the Johns Hopkins Physical Science-Oncology Center where she is studying the effects of low oxygen (hypoxia) on the tumor growth and blood vessel formation. The AHA funding will support her work on regulating hypoxia in hydrogels for vascular regeneration. The award is worth approximately $400,000 over five years.

Learn more about the Gerecht lab here.

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

 

Sciencescape rescues researchers from never-ending flow of published data

Screen Shot 2014-12-03 at 1.28.38 PMI like to listen to as much new music as I can. But I realized long ago that there would never be enough hours in the day or days in my lifetime to sift through all the new stuff to discover cool new tunes, even in the genres I preferred.

Scientists and engineers have similar problems staying current with research relevant to their disciplines. A report published in November 2012 by the International Association of Scientific, Technical and Medical Publishers estimated that 1.8 million papers are published in 28,000 academic journals every year. That’s a lot of data and a lot of discussion about that data. Another study published in 2007, reported that very little of this research is ever read by anyone. Only a wee bit of it is going to help your finish your dissertation, refine your protocol or provide the foundations to your next big breakthrough.

Thankfully some smart folks at Sciencescape.org have figured out a nifty way for you to sift through this mountain of virtual paper. Sciencescape pulls in data from available online journal databases, like PubMed, Google Scholar and many more going back to 1880. Using your chosen criteria, Sciencescape creates sort of a news feed of published research that may be important for you. You can use search criteria such as author, topic, journal name, and publication date. You can even keep track of research coming out of a specific lab or follow authors as you would follow people on Twitter.  Sciencescape uses Eigenfactor metrics, which pinpoints papers that are highly cited and by high impact journals, both good indicators that a paper is worth checking out. It helps you find the quality research. Sciencescape can even assist with finding papers on topics for your undergraduate journal club.

One especially cool feature of Sciencescape is the ability to set up a laboratory profile where the work of lab members can feed into one stream. That way you know what your colleagues  at the next lab bench or down the hall are publishing. By breaking down these virtual walls between labs, departments and even universities, Sciencescape facilitates collaborations, which is something Johns Hopkins Institute for NanoBioTechnology has fostered since inception.

The Sciencescape user interface is attractive and easy to read, which entices even someone like me (who is not actively engaged in research) into exploring a topic. It did not take me very long before I had fallen down a rabbit hole of knowledge! You can save papers to a library or share them on social media like Facebook and Twitter, because of course your mom and your college buddies want to know you are keeping up with current research in nanobiotechnology!

Sciencescape was listed by The Scientist magazine as a Top Innovation for 2014, and it is evident as to why. Now if they could only come up with an Eigenfactor metric that would work for music so I could avoid listening to music I probably wouldn’t like. PS, this is not a paid advertisement for Sciencescape, I just thought it seemed really useful. I am now keeping track of several INBT faculty researchers on Sciencescape.

Watch a video on Sciencescape here.

 

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

Research Remix calls for posters

Johns Hopkins Digital Media Center (DMC) is inviting artists and researchers to collaborate on works of visual art that expand on the theme of the original science. The goal of the project is to make research more accessible and engaging to the public.

research-remix-draft-feature1To begin the collaboration process students, staff or faculty are asked to submit posters (presumably ones you don’t need anymore) to the DMC, located in the Mattin Center on the Homewood campus. The posters will be used as source material and to be reimagined and re-interpreted by a group of visual artists, including some artists from MICA. The posters and the ideas they present could be visualized as an illustration, painting, sculpture, computer animation or something else entirely.

Both researchers and artists are needed for this project, which begins now. During the visualization process, artists and researchers will meet to discuss the poster content and the resulting artist’s interpretation. The meet-and-greet will take place in February 2015. The project will culminate in April 2015 with a gallery exhibition at JHU.

Read more about this project at this link. If you are interested in participating in the DMC’s Research Remix send an email to digitalmedia@jhu.edu and put REMIX in the subject line.

INBT postdoc launches new UMD College Park lab

Kimberly Stroka is busy winding up her postdoctoral training in the chemical and biomolecular engineering laboratory of Professor and Department Chair Konstantinos Konstantopoulos at Johns Hopkins University. She was affiliated with  the Institute for NanoBioTechnology (INBT) and the Johns Hopkins Physical Sciences-Oncology Center.

Dr. Kim Stroka

Dr. Kim Stroka

But starting in January 2015, Dr. Stroka will return to her graduate alma mater to launch her Cell and Microenvironment Engineering Lab at the University of Maryland, College Park. Dr. Stroka earned her PhD in bioengineering from UMCP in 2011. Dr. Stroka is looking for graduate students (and others) who would be interested in joining her lab.

She summarizes her laboratory research goals below:

“Our research lies at the interface of cell engineering, nano/microtechnology, and quantitative mechanobiology, and integrates principles and techniques from engineering, biology, and physics in order to address questions related to physiological processes and diseases such as cancer and cardiovascular disease. Our goal is to utilize this highly interdisciplinary approach in order to create relevant in vitro models of multi-scale biological systems (from intracellular signaling to single cell behavior to multicellular complexes), to understand how cells respond to physical and biochemical cues from their microenvironment, and to develop regenerative therapies for diseases using engineering strategies. We are particularly interested in questions at the interface of nano/microtechnology and blood-brain barrier mechanobiology, nuclear mechanics, and stem cell engineering.”

Please visit Dr. Stroka’s laboratory website site for more details: http://kimberlystroka.weebly.com/.

You may also email her directly at kstroka@jhu.edu.

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Bring your best ideas to the neuro start-up challenge

The National Institutes of Health, Center for Advancing Innovation and the Heritage Provider Network have set up a business plan and biotech start-up “challenge” for graduate students and postdoctoral fellows with bright ideas to commercialize neuro-related inventions. Similar to last year’s Breast Cancer Challenge, the inventions are derived from the NIH intramural portfolio.

neurochallengThe Challenge will feature 16 brain related inventions (including various neurological diseases and cancer) that have commercial viability and are important to public health, with the primary goal being to stimulate the creation of start-up businesses based upon these inventions.  Letters of Intent will be accepted until November 30, 2014.

This is a fantastic opportunity for graduate students, post-docs, entrepreneurs and others interested in making an impact on brain health to join the challenge, learn the business of science, be an entrepreneur and have the opportunity to raise seed funding.

More information about this challenge can be found at this link or by contacting Rosemarie Truman at rt@ thecenterforadvancinginnovation.org, 202-438-2208. The Neuro Start-up Challenge is also on Facebook at this link.

Save the date for Johns Hopkins Institute for NanoBioTechnology’s annual symposium “Neuro-X,” May 1, 2015 in the Owens Auditorium at the Johns Hopkins medical campus. More details can be found at our Facebook event page.

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

INBT’s fall student symposium Nov. 7

An important opportunity in graduate school is to get peer and mentor feedback on results. One of the best ways to do that is to share what you have been working on with your colleagues at a symposium.

Jordan Green

Jordan Green

Come hear the latest updates from Johns Hopkins Institute for NanoBioTechnology’s research centers on Friday, November 7 from 9 a.m. to 12:30 p.m. in the Great Hall at Levering on the Homewood campus! Students affiliated with laboratories from the Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins Center of Cancer Nanotechnology Excellence and INBT will present at this student-organized symposium. This event is free and open to the Johns Hopkins community. Refreshments provided.

The keynote faculty speaker is Jordan Green, associate professor at Johns Hopkins Department of Biomedical Engineering. Green was recently named one of Popular Science magazine’s “Brilliant 10.” Breakfast, networking and introductions begin at 9 a.m.

Student speakers and topics include:
**Kristen Kozielski – Bioreducible nanoparticles for efficient and environmentally triggered siRNA delivery to primary human glioblastoma cells. Jordan Green Lab. 9:30-9:45 a.m.

**Angela Jimenez – Spatio-temporal characterization of tumor growth and invasion in three-dimensions (3D). Denis Wirtz Lab. 9:50-10:05 a.m.

**Amanda Levy – Development of an in vitro system for the study of neuroinflammation. Peter Searson Lab. 10:10- 10:25 a.m.

**Max Bogorad – An engineered microvessel platform for quantitative imaging of drug permeability and absorption.  Peter Searson Lab. 10:30-10:45 a.m.

**Greg Wiedman – Peptide Mediated Methods of Nanoparticle Drug Delivery. Kalina Hristova Lab. 10:50 to 11:05 a.m.

**Jordan Green – Particle-based micro and nanotechnology to treat cancer 11:10 a.m. – 12:10 p.m.

Please RSVP on our Facebook event page here.

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

Boarding the research bandwagon

The story of how I joined Johns Hopkins Institute for NanoBioTechnology (INBT) is actually one of those moments where it just hits you – Why haven’t I thought about doing this before? It started with me being back at home during the winter of my sophomore year, meeting friends of my parents and answering the most common question: Where do you study? One of the reactions that stuck with me the whole night was “Wow, how does it feel to be in the center of the most cutting-edge research?” This made me realize how I’d been oblivious to one of the things I would love to get involved in.

Better one and a half years late than never, I decided to join the research bandwagon as well. I started going through the profiles of labs on Homewood campus, looking for a topic that would make me want to be there in lab every free minute during the year. I finally found one that sparked my curiosity: the Denis Wirtz Lab. Dr. Wirtz is the Smoot Professor in the Department of Chemical and Biomolecular Engineering and also the University’s Vice Provost for Research.

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Working in the lab!

Though at the time most of the stuff I read about the Wirtz lab went over my head, I knew that cancer was something I had always wanted the world to be rid of. Seeing near and dear ones succumb to it was one of the most excruciating things which I wanted no one to experience in the future. Fascinated by the approach taken by Dr. Wirtz, I shot him off an email and to my amazement, I got an email back within the hour, “Sent to my grad students, look forward to working with you. d”. The next day I was scheduled to be back in Baltimore, and the day after that, I was a part of Wirtz lab.

During my training, I remember asking one of my peers “How in the world can I remember all these procedures, let alone do them?” She simply smiled and said, “You’ll see”. In a few weeks, I found myself doing those very procedures, one step after another as if it were a reflex action. I would most definitely attribute me being able to do this to my grad student Hasini Jayatilaka (don’t kill me for calling you out!). At the end of the day, what I felt it boiled down to, was realizing that the person I work for was in the same shoes five-seven years ago as I was now, and she wouldn’t expect anything unrealistic out of me. Once you embrace the challenge ahead, knowing that there is no need to be intimidated, you’re good to go.

The best part of being involved in research, apart from the work you do, is sitting in class in a lecture hall and suddenly tune in to the professor talking about something that you do in lab each day. That moment cements your understanding of why you did what you’ve been doing for so many days, it connects the dots in your mind, and that moment is when you’ve completed the full circle between theory and practice.

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Our team at a poster presentation over the summer.

For me personally, having to come to lab got me into a disciplined schedule. I had a fixed time for all days of the week now to wake up (which for me used to be the latest possible time before), since if I had no morning classes, I was in lab. It helped me a lot with my time management skills, with me cutting down on TV shows and sporadic naps. To my surprise, it did not affect the amount of time I spent with my friends, as the reduction in TV shows and naps was (extremely) disturbingly enough to keep every other aspect of my daily schedule the same. Being surrounded in lab by people in similar academic disciplines also gets me a ton of advice on classes. It’s like my own little “rate-my-professor” that encourages me to definitely take some class if it is “the best class I will take at Hopkins”. At times, it’s also a ‘learning den’ where I can get help with classes if I need to. Getting involved in a research lab also came with social outings with the team, with our dinners enabling us to get to know each other on a more personal level. I feel that this in a big way contributed to the chemistry we have while working with each other, made us comfortable spending time with each other at work.

At this point, after nine exciting months, including a fully lab-packed summer, I feel that this continues to be one of the best decisions I made so far. I do not regret being here every day, but take pride in saying “I need to be in lab”. One of the most cherished take-away for me is developing a sense of accountability for my actions, which I feel is an important aspect in life. I would definitely encourage being involved in research while at Hopkins as you have nothing to lose but so much to gain.

Pranay Tyle, is a junior in Chemical and Biomolecular Engineering minoring in Economics, and hopes to one day manufacture low cost medicine accessible to those in dire need across the globe.

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

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).

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

 

Summer interns for Johns Hopkins Applied Physics Lab sought

In 2013, a partnership with the Johns Hopkins University Applied Physics Laboratory (APL) and the Whiting School of Engineering launched APL/WSE Summer Program in Undergraduate Research or SPUR program. Whiting School of Engineering undergraduates who were selected for this prestigious program spent an incredible summer at APL working with mentors and conducting research as paid SPUR Scholars.

The application process for SPUR Scholars for the summer of 2015 is now open!

labwarestockThe program seeks highly qualified and motivated WSE undergraduates to be 2015 SPUR Scholars. To learn more, you are invited to attend the 2014 SPUR Poster and Information Session from 4 to 6 p.m. Tuesday, October 21 in the Glass Pavilion on the Johns Hopkins University Homewood campus. Refreshments will be provided. Please register for the event today at this link.

At the event, last summer’s SPUR Scholars will present a poster session about their research findings and representatives from APL and WSE will be there to answer students’ questions about the application and selection process. For more information on the SPUR program visit this link.

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