Pluripotent stem cells hold key to blood vessel formation

Pluripotent stem cells, those cells capable of transforming into any type of tissue in the human body, hold the key to one of science’s biggest challenges: the formation of new blood vessels.

Researchers in the laboratory of Sharon Gerecht, associate professor of chemical and biomolecular engineering in the Whiting School of Engineering at Johns Hopkins University, have demonstrated a method that causes these powerful cells to form a fresh network of blood vessels when transplanted in mice. Shawna Williams, writer at the Johns Hopkins School of Medicine, reports here on this new research, which was published online this week in the Proceedings of the National Academy of Sciences. You can find the article here.

Shown are lab-grown human blood vessel networks (red) incorporating into and around mouse networks (green). (Gerecht Lab/PNAS)

Shown are lab-grown human blood vessel networks (red) incorporating into and around mouse networks (green). (Gerecht Lab/PNAS)

Here’s a comment from Gerecht, who is affiliated with both Johns Hopkins Physical Sciences–Oncology Center and Institute for NanoBioTechnology:

“In demonstrating the ability to rebuild a microvascular bed in a clinically relevant manner, we have made an important step toward the construction of blood vessels for therapeutic use … Our findings could yield more effective treatments for patients afflicted with burns, diabetic complications and other conditions in which vasculature function is compromised.”

The Gerecht lab, in collaboration with researchers at the School of Medicine, has been working on this puzzle for some time. One important stride in this current work is that the vessels are forming and persisting in a living animal and not just in a culture in a flask.

Says lead author and doctoral student in biomedical engineering, Sravanti Kusuma:

“That these vessels survive and function inside a living animal is a crucial step in getting them to medical application.”

You can read about some of the Gerecht lab’s previous findings in this particular pursuit in the articles listed below:

Engineers Coax Stem Cells to Diversify 

Research Seeks to Turn Stem Cells into Blood Vessels

 

Mentors model academic pathway

Editor’s Note: This article originally appeared in the Johns Hopkins Nano-Bio Magazine and was written by Colin Paul, a third-year graduate student at Johns Hopkins University in the Konstantopoulos lab. He invites anyone with questions about or interest in the Incentive Mentoring Program to contact him at colin.paul@incentivementoringprogram.org.

When I was in high school, I had an inspiring chemistry teacher. He was funny, he rewarded hard work, and he let us light salt fires in paths around the soapstone lab benches in his classroom. He stayed after school to help my twin brother and me build a “ChemE Car” that used a chemical reaction to stop after a given distance, and we placed second in a competition for local high schools held by the University of Tulsa. He made the subject interesting, and his passion for it was contagious.

Charli

Charli Dawidczyk mentors Baltimore high school students. Photo by Mary Spiro

Before taking his class, I wasn’t sure what I wanted to study in college. But as the year progressed, his mentorship helped me decide to pursue chemical engineering, and I’m still doing that as a graduate student at Johns Hopkins University.

As a scientist, I hope I can inspire others to consider a career in science. Mentorship is particularly important to underrepresented groups in the sciences, such as minorities or women. It’s so important that the National Institutes of Health supports science education and outreach through its Office of Science  Education, and the National Science Foundation has made it a goal “to expand efforts to increase participation from underrepresented groups and diverse institutions throughout the United States in all NSF activities and programs.”

Johns Hopkins University is also increasingly leading efforts to improve Baltimore communities. In an editorial published in the magazine of the School of Advanced International Studies, Hopkins president Ron Daniels stated the need for Hopkins to help revitalize Baltimore and outlined some of the initiatives to do so.

Faculty, staff, and trainees at Johns Hopkins Institute for NanoBioTechnology (INBT) are challenged to become more involved in mentoring pre-college students. Recently, INBT partnered with the Incentive Mentoring Program (IMP) to hold a “Science Day” for students at the Academy for College and Career Exploration (ACCE), a Baltimore high school near the Hopkins Homewood campus. IMP, founded in 2004 by Hopkins biomedical engineering graduate Sarah Hemminger, pairs mentors with underperforming Baltimore city high school students who were at risk of not graduating. The program has grown to incorporate several hundred volunteers from the East Baltimore and Homewood Hopkins campuses.

Colin Paul, center, looks on as high schoolers us liquid nitrogen to make ice cream. Photo by Mary Spiro.

Colin Paul, center, looks on as high schoolers us liquid nitrogen to make ice cream. Photo by Mary Spiro.

IMP provides comprehensive mentoring and tutoring to enrolled students, offering educational, legal, and career support to the students and their families. IMP is not merely a tutoring program in which volunteers help students with homework. Instead, it provides students with the social support they may otherwise lack. Teams of five to six mentors are assigned to each student, and these mentors coalesce into an extended family around the student, many of whom come from environments where even graduating from high school is an obstacle. So far, all of the students enrolled in IMP have earned their high school diplomas or equivalent degree.

As IMP grew, students from the laboratories of INBT-affiliated faculty members Peter Searson, Konstantinos Konstantopoulos, Hai-Quan Mao, Justin Hanes, and Andre Levchenko started to get involved. INBT sought to unite the groups for an event to encourage science education among the IMP students. The idea to hold a joint event came from Andrew Wong of the Searson lab, an INBT trainee who has been instrumental in IMP’s community service activities. I led the event, held on February 27, with Charli Dawidczyk, a doctoral student from the Searson lab.

Our first activity was to build a simple speaker using foam plates, magnets, and wire. Students learned how electromagnetic forces, whose strength and frequency vary depending on the song, deflect the foam plate to create sound waves when the plate is glued to a magnet with a coil of wire around it. The speakers weren’t loud, but everyone participated, even though they might have been more interested in the strong neodymium magnets.

Next, we moved from physics to chemistry and made liquid nitrogen ice cream. We discussed how liquid nitrogen boils at -321°F, much colder than water, and how it would very quickly freeze our liquid ice cream mix. The students made excellent chefs and were excited to see water vapor roil over the lip of the bowl as liquid nitrogen was stirred in to freeze the cream. The recipe got several thumbs up, and the demonstration really held their attention.

I hope the students saw how science comes up in everyday life, even in things we don’t always think about, like music and cooking. By having fun and doing experiments with their mentors and friends, they may realize that a career in science is an option for them. In many ways, IMP is an experiment on how to provide extended families for at-risk students. Problems are tackled on a trial-and error basis by volunteers from a variety of backgrounds. Often, an initial solution does not work; but, just like in the lab, we think about what went wrong and try to improve our approach.

The PIs at INBT have encouraged us to make a difference in the community. I’m grateful that my education at Hopkins has included IMP and the wonderful students and volunteers comprising the organization.

Overcoming drug delivery barriers

Editor’s Note: The following is a summary of one of the talks from the 2013 Nano-bio Symposium hosted by Johns Hopkins Institute for NanoBioTechnology held May 17. This summary was written by Randall Meyer, a doctoral candidate in the biomedical engineering and a member of the Cancer Nanotechnology Training Center. Look for other symposium summaries on the INBT blog.

Nanotechnology bears a multitude of possibilities to systematically and specifically treat many well-characterized and currently untreatable diseases.  Despite this, there exist multiple barriers to its development including challenges related to delivery in the human body.

justin_hanes

Justin Hanes, a professor of Chemical and Biomolecular Engineering at Johns Hopkins University, highlighted some of the exciting advances that his laboratory has developed to overcoming these challenges.  According to Hanes, one of the primary functions of nanobiotechnology is to enable a therapy to be delivered to a specific location and only remain there for as long as it is needed.  He likened this idea to applying weed poison to a rose garden.  You only want to apply a little bit of poison to a targeted area, not flood the whole garden.  Unfortunately conventional cancer chemotherapy is like flooding the garden, but only 1 percent of the drug reaches the tumor.  Hanes stated the goal of his work is to flip that so that all but 1 percent of the drug makes it to the site of delivery.

With that in mind, Hanes summarized two stories from his lab of ideas that are successfully being translated from bench to bedside.  One therapy involves the use of custom designed nanoparticles that are capable of penetrating the mucus layers of various human tissues to enable a controlled release of drug into the body.  The second therapy involves the use of injectable particles to the eye that inhibit blood vessel formation,  which is related to diseases such as macular degeneration.

These therapies are being developed by biotech companies launched by Hanes, GrayBug and Kala Pharmaceuticals.

Burn healing gel could soon be commercialized for veterinary use

Hope for severe burns could lie in the healing action encouraged by a colorless, odorless “hydrogel” developed by Johns Hopkins Institute for NanoBiotechnology affiliated researchers. The Johns Hopkins Engineering Magazine summer edition featured a story here on this work, occurring in the laboratory of chemical and biomolecular engineering associate professor, Sharon Gerecht.

Screen Shot 2013-07-01 at 2.20.27 PMNews of the original research was posted here on the INBT blog in December 2011. However, the pain and suffering experienced by third-degree burn sufferers is long-lasting and this work rightly deserves to be re-visited. The original study, done in conjunction with faculty in the Department of Pathology at the Johns Hopkins School of Medicine and the Johns Hopkins Burn Center at Bayview Medical Center, demonstrated for the first time a treatment that could not only aid in healing but practically restore the skin in the tested animals to a healthy state. Use of the hydrogel was tested on mice, and after just a few weeks, skin had regrown to a nearly scar-free state that could even regrow hair. The team is now looking a testing the gel with pigs.

The funny thing is, is that Gerecht and company are not even sure why the hydrogel works the way it does.

The Whiting School of Engineering magazine article highlights the potential commercialization timeline for the hydrogel, that is, when will a product based on this new technology be available for humans? That is a question that folks here at INBT and those affiliated with this work have been receiving nearly once a week since this research was first published. Now, maybe we will have an answer for all those who could potentially benefit from this important and yet mysterious discovery.

Making therapeutic proteins last longer

Happy TRAILs to you: PEGylation of proteins through complementary interactions between a His-tag and a Ni2+ complex of nitrilotriacetic acid (NTA, see picture), a well-established practice in protein research, was used to improve the half-life of therapeutic proteins in the blood following systemic administration in vivo. Animal models show that this site-specific modification improves the efficacy of modified TRAIL proteins.

Happy TRAILs to you: PEGylation of proteins through complementary interactions between a His-tag and a Ni2+ complex of nitrilotriacetic acid (NTA, see picture), a well-established practice in protein research, was used to improve the half-life of therapeutic proteins in the blood following systemic administration in vivo. Animal models show that this site-specific modification improves the efficacy of modified TRAIL proteins.

Proteins are responsible for pretty much everything in the human body. When there is a problem with the proteins, it usually leads to disease.

Protein therapy shows enormous potential for treating disease. But sometimes the proteins in a therapeutic treatment break down or are metabolized before they ever reach their target destination.

In a recent paper published in Angewandte Chemie, researchers from the laboratories of Martin Pomper (radiology oncology) and Seulki Lee (radiology, Center for Nanomedicine) at the Johns Hopkins School of Medicine and developed a simple method to validate protein drugs in animal models, said Lee. An illustration related to the paper appeared on the cover of the journal.

“We show that we can extend the half-life, that is, the amount of time the drug stays in the blood, while maintaining the activity of the model protein drug, TRAIL,” said one of the lead authors Maggie Swierczewska. “This has great implications for drug screening and validation methods, especially for the growing protein drug market.”

According to the paper, by attaching a molecule of  polyethylene glycol (PEG) to certain sites on the TRAIL protein drugs through an already well known method, the half-life of the drug could be extended without affecting its beneficial activity.

Authors on this paper include Tae Hyung Kim, Magdalena Swierczewska, Yumin Oh, AeRyon Kim, Dong Gyu Jo, Jae Hyung Park,  Youngro Byun, Scheherazade Sadegh-Nasseri, Martin G. Pomper, Kang Choon Lee, Seulki Lee. Author affiliations include the departments of Radiology and Pathology at the Johns Hopkins School of Medicine, the Johns Hopkins Center of Cancer Nanotechnology Excellence, the Johns Hopkins Institute for NanoBioTechnology, Center for Nanomedicine and collaborators at Sungkyunkwan University and Seoul National University, both in Korea.

Reference: Kim, T. H., Swierczewska, M., Oh, Y., Kim, A., Jo, D. G., Park, J. H., Byun, Y., Sadegh-Nasseri, S., Pomper, M. G., Lee, K. C. and Lee, S. (2013), Mix to Validate: A Facile, Reversible PEGylation for Fast Screening of Potential Therapeutic Proteins In Vivo. Angew. Chem. Int. Ed.. Vol. 52, Issue 27, pages 6880-6884, doi: 10.1002/anie.201302181

Lindau: where the Nobel Laureates gather

If you want to rub elbows with Nobel Laureates, the place to be this week is Lindau, Germany. Three of the four Johns Hopkins University graduate students attending the 63rd Annual Lindau Nobel Laureate meeting, which is dedicated to chemistry thie year, work in Institute for NanoBioTechnology affiliated laboratories. The meeting runs from June 30 to July 5 and will host more than 550 young researchers from 78 countries.

Allison Chambliss, a doctoral student in chemical and biomolecular engineering from the laboratory of Denis Wirtz; Sravanti Kusuman, a doctoral student in biomedical engineering from the laboratory of Sharon Gerecht; and Allix Sanders, a graduate student in chemistry from the laboratory of J.D. Tovar,  were chosen to attend along with 71 other top U.S. graduate student researchers. This year’s group is sponsored by the U.S. Department of Energy, Mars, Incorporated, the National Science Foundation, and the Oak Ridge Associated Universities (ORAU).

Before she left, Allison said she was excited about the opportunity to interact with successful and well known researchers, which is harder to do at big conferences. Essentially, she and the others will be chatting with the “rockstars” of science. Allison was able to attend despite also having a summer internship with Novozyme in Raleigh, NC, where she is working in their R&D department on biofuels.

“I liked hearing about how it was so interactive and that there will be people from all over the world. And then the fact that there will be Nobel Laureates, you don’t get the chance to meet someone like that every day, “ Allison said. She also sees this as an opportunity to network in case she wants to do a postdoctoral fellowship in another country. “I will be meeting people from labs all over the place and also people in both academia and industry.”

Allison’s current research in the Wirtz lab involves using high-throughput cell phenotyping to look at the physical characteristic of cells on a single cell basis and how physical attributes can impact a cell genetically. Allison did her undergraduate work at Virginia Tech.

Sravanti’s did her undergraduate work at MIT. Her research in the Gerecht lab involves using pluripotent stem cells and a specially engineered synthetic matrix to grow a micro-vasculature (tiny blood vessels).

“These are the seminal leaders in their field, and in many cases, they are the ones that created their fields, so I just think it will be great to learn the science from their standpoint,” Sravanti said. “You know, like what obstacles did they have to overcome to prove their point, since all their findings would be really novel.”

She is also interested in learning what inspires and keeps these leading figures going. “This is also a more intimate setting,” Sravanti added. “There are lectures in the morning but in the afternoon there are smaller roundtable discussions where you can get more intimate with whichever Nobel Laureate you choose to talk to.

Allix Sanders is working on a project in the Tovar lab that incorporates large, unique chromophores comprised of extended pi-conjugated networks into peptide chains. Following self-assembly, the photophysical characterizations of the supramolecular polymers will be investigated with the future goal of creating useful electronic materials. Allix did her undergraduate studies at Lebanon Valley College.

The fourth Johns Hopkins University student is Joseph Schonhoft, a doctoral student in the biophysics department, which is part of the Krieger School of Arts and Sciences. He works in the laboratory of James Stivers at the School of Medicine. His research involves facillitated diffusion mechanisms of DNA repair enzymes.

According to information from ORAU, Nobel Laureates have annually convened in Lindau since 1951 to have open and informal meetings with students and young researchers from around the world. Laureates and students exchange ideas, discuss projects and build international networks throughout the week. All attendees must pass through a competitive application and selection process managed by the Council for the Lindau Nobel Laureate Meetings. Throughout the week, the 35 participating Laureates will lecture in the mornings on the topic of their choice related to chemistry and participate in smaller question and answer sessions in the afternoons. Students will also interact with the Laureates and other international students during the week for more informal discussions. This year, with the addition of science master classes, a select few researchers will have the opportunity to present their research to a Nobel Laureate and a small group of their peers.

For more information regarding the 63rd Lindau Meeting of Nobel Laureates and Students, visit the ORAU–Lindau website. The ORAU-Lindau website and all logistical arrangements for the participants are being administered by the Oak Ridge Institute for Science and Education, a DOE institute managed by ORAU.

Lab coats are summer gear for high school researchers

You don’t think of a lab coat as summer wear for teens, but we don’t quite feel like it’s summer around here until our research interns have arrived. Early in June, INBT’s undergraduate nano-bio researchers arrived. This week our high schoolers in the Summer Academic Research Experience (SARE) scholars got started.

SARE pairs specially selected teens with university mentors who guide them through a mini research project. At the end of their time here, they hold a small poster session. The students gain valuable work skills, learn about scientific careers, get tutoring help, practice their writing, gather data for their projects and earn some cash for the future. Students in the program are recruited from the Boys Hope Girls Home of Baltimore program, The SEED School of Maryland and The Crossroads School, all of which assist in differing ways with in the education, housing, tutoring  and counseling of promising young people from disadvantaged circumstances.

The SARE program was launched in 2009 by Doug Robinson, professor in the cell biology department at the School of Medicine, and is funded jointly by the medical school and Johns Hopkins Institute for NanoBioTechnology.

This year’s SARE scholars include: Diana Bobb is being mentored by Makoto Tanigawa in the Takanari Inoue Lab in the Department of Cell Biology; Kaleel Byrd is being mentored by Ryan Vierling in the Caren Meyers Lab in the Department of Pharmacology; Milan Dower is being mentored by Tom Lampert in the Peter Devreotes Lab in the Department of Cell Biology; Jewel Herndon is being mentored by Herschel Wade in his lab in the Department of Biophysics; De’Sean Markley is being mentored by Hoku West-Foyle in the Douglas Robinson Lab in the Department of Cell Biology

2013 summer nano-bio research interns get to work

Johns Hopkins Institute for NanoBioTechnology welcomes its summer 2013 research interns. Students arrived from universities from across the nation to conduct 10 weeks of research in INBT sponsored laboratories. Interns are supported by the National Science Foundation Research Experience for Undergraduates  program through INBT and receive housing and a stipend during their tenure at Hopkins. At the end of their research project, students will present posters describing their work with other Hopkins students in a university-wide poster session.

This year’s students include:

Shantel Angstadt is from Elizabethtown College. She is working in the cell biology laboratory of Doug Robinson at the Johns Hopkins School of Medicine.

Hamsa Gowda is from UMBC. She is working in the materials science and engineering laboratory of Peter Searson at the Whiting School of Engineering.

Toni-Rose Guiriba is currently studying at Baltimore County Community College. She is working in the radiation oncology laboratory of Robert Ivkov at the School of Medicine.

Sarah Hansen is from the University of Virginia and is working with Jordan Green in his biomedical engineering laboratory at the School of Medicine.

Devante Horne studies at Clemson University and is conducting research with Honggang Cui in his chemical and biomolecular engineering laboratory at the Whiting School of Engineering.

Cameron Nemeth is from the University of Washington and is working in the materials science and engineering laboratory of Hai-Quan Mao at the Whiting School of Engineering.

Victoria Patino studies at Carnegie Mellon University and also works in the materials science and engineering laboratory of Hai-Quan Mao.

Camilo Ruiz studies at MIT and works with Deniz Wirtz in his chemical and biomolecular engineering laboratory at the Whiting School of Engineering.

Marc Thompson studies at North Carolina A & T State University and is conducting research in the biomedical engineering laboratory of Warren Grayson at the School of Medicine.

Breanna Turner is from Fort Valley State University and works in the materials science and engineering laboratory of Margarita Herrera-Alonso at the Whiting School of Engineering.

Jordan “Jo” Villa is from The College of William and Mary and conducts research in the chemistry laboratory of J.D. Tovar in the Krieger School of Arts and Sciences.


 

 

 

 

Fraley nets $500K Burroughs Wellcome Fund award for microfluidics work

Stephanie Fraley (Photo: Homewood Photography)

Stephanie Fraley (Photo: Homewood Photography)

A Johns Hopkins research fellow who is developing novel approaches to quickly identify bacterial DNA and human microRNA has won the prestigious $500,000 Burroughs Wellcome Fund (BWF) Career Award at the Scientific Interfaces. The prize, distributed over the next five years, helps transition newly minted PhDs from postdoctoral work into their first faculty positions.

Stephanie Fraley is a postdoctoral fellow working with Samuel Yang, MD, in Emergency Medicine/Infectious Disease at the Johns Hopkins School of Medicine and Jeff Wang, PhD, in Biomedical Engineering with appointments in the Whiting School of Engineering and the medical school. The goal of her work is to develop engineering technologies that can diagnose and guide treatment of sepsis, a leading cause of death worldwide, while simultaneously leading to improved understanding of how human cells and bacterial cells interact.

“Sepsis is an out of control immune response to infection,” Fraley said. “We are developing tools that are single molecule sensitive and can rapidly sort and detect bacterial and host response markers associated with sepsis. However, our devices are universal in that they can be applied to many other diseases.”

Fraley is using lab-on-chip technology, also known as microfluidics, to overcome the challenges of identifying the specific genetic material of bacteria and immune cells. Her technology aims to sort the genetic material down to the level of individual sequences so that each can be quantified with single molecule sensitivity.

“Bacterial DNA is on everything and contamination is everywhere, so trying to find the ones associated with sepsis is like the proverbial search for the needle in the haystack,” Fraley said. “With microfluidics, we can separate out all the bacterial DNA, so instead of a needle in a haystack, we have just the needles.”

Another advantage to Fraley’s novel technology is that it will assess all the diverse bacterial DNA present in a sample, without presuming which genetic material is important. “Bacteria are constantly evolving and becoming drug resistant,” she said. “With this technology, we can see all the bacterial DNA that is present individually and not just the strains we THINK we need to look for.”

Fraley’s award will follow her wherever her career takes her. The first two years of the prize fund postdoctoral training and that last three years help launch her professional career in academia. During the application process, she had to make a short presentation on her proposal to BWF’s panel of experts. “It was like the television show ‘Shark Tank’ but for scientists,” she laughs. “ The panelists gave me many helpful suggestions on my idea.”

Fraley earned her bachelor’s degree in chemical engineering from the University of Tennessee at Chattanooga and her doctorate in chemical and biomolecular engineering with Denis Wirtz, professor and director of Johns Hopkins Physical Sciences-Oncology Center. Wirtz is associate director for the Institute for NanoBioTechnology and Yang and Wang also are INBT affiliated faculty members.

BWF’s Career Awards at the Scientific Interface provides funding to bridge advanced postdoctoral training and the first three years of faculty service. These awards are intended to foster the early career development of researchers who have transitioned or are transitioning from undergraduate and/or graduate work in the physical/mathematical/computational sciences or engineering into postdoctoral work in the biological sciences, and who are dedicated to pursuing a career in academic research. These awards are open to U.S. and Canadian citizens or permanent residents as well as to U.S. temporary residents.

INBT professional development seminars schedule announced

As an outreach to its students and the university community at large, Johns Hopkins Institue for NanoBioTechnology offers four professional development seminars during the summer.  All seminars are held on select Wednesdays in Remsen 101 from 10:45am – 12pm.

The seminar schedule is as follows:

  • June 12 – Topic: I got my PhD, now what? A panel discussion 

Panel: Justin Galloway, PhD, Entrepreneurship; Associate Professor of Chemical and Biomolecular Engineering Honggang Cui, Academia; Kate Malachowski, ChemBE doctoral candidate, Industry/ Government; Ramsay Kraya, postdoctoral fellow in the Searson Lab, materials science and engineering

  • June 26 – Topic: How to promote yourself and the benefits of networking

Speaker: Tom Fekete, INBT’s director of corporate partnerships

  • July 10 – Topic: Why you should consider grad school and how do you prepare?

Speaker: Eric Hall,  associate director of the JHU Career Center

  • July 24 – Topic: INBT Film Festival, featuring short films made by students in Science Communication for Scientists and Engineers

Hosted by: Mary Spiro, INBT’s science writer

No RSVP is needed. The seminars are free and open to university students, faculty, staff and visitors.