Siebel scholars demonstrate INBT’s multidisciplinary advantage

Siebel scholar Laura Ensign. Photo by Marty Katz.

Four of the five recently named Johns Hopkins University graduate students who were listed among the 2013 Siebel Scholars are affiliated with Johns Hopkins Institute for NanoBioTechnology laboratories. Three of the four were also part of INBT’s Nanobio IGERT, or Integrative Graduate Education Research Traineeship, a National Science Foundation funded program. The Siebel Scholars program recognizes the most talented students at the world’s leading graduate schools of business, bioengineering, and computer science.

INBT affiliated winners include Laura Ensign, Mustapha Jamal, Garrett Jenkinson and Yi Zhang. Ensign, Jamal and Jenkinson were INBT IGERT fellows. All note that their involvement with INBT to one degree or another has played a role in their academic success at Hopkins.

Laura Ensign, in the Department of Chemical and BioMolecular Engineering, works in the laboratory of Justin Hanes, who is director of the Center for Nanomedicine and investigator with the Center of Cancer Nanotechnology Excellence (CCNE). Ensign’s research involves understanding the mucus barrier in the female reproductive tract and how it protects and also inhibits the delivery of drugs to this part of the body. Using specially engineered mucus penetrating nanoparticles designed in the Hanes labs, she is working on more effective drug delivery systems. Ensign is listed as an inventor on three patents that have been licensed to private industry.

“As an engineer, the multidisciplinary nature of INBT has allowed me to do research that has the potential to help patients in the clinic,” Ensign said. Furthermore, Ensign noted that having two advisors, a requirement for INBT’s IGERT program, played an important role in her graduate work and discoveries. In addition to being advised by Hanes, Ensign also was mentored by Richard Cone, professor in the Department of Biophysics in the Krieger School of Arts and Sciences. “The trajectory of my research has been greatly influenced by having two advisers with different backgrounds. My research has included engineering and formulation aspects, as well as biological and translational aspects, resulting in higher impact results with broader implications. “

Siebel scholar Mustapha Jamal

Mustapha Jamal, also in the Department of Chemical and Biomolecular Engineering, worked in the laboratory of associate professor David Gracias. Jamal has developed self-assembling structures that provide a framework for 3D tissue culture. In addition, these self-assembling structures let him study how geometry affects cell behavior. Jamal is a co-inventor on a patent application in connection with this research.

“Working in a multidiscplinary lab has helped me engineer miniaturized 3D cell culture platforms utilizing techniques from seemingly disparate research areas: semiconductor processing and tissue engineering,” Jamal said. “With a bit of creativity, this diverse skill set has proven useful in forging exciting and fruitful collaborations and should serve me well for years to come. From the annual INBT Symposium to the courses and workshops, I have shared my own research with the community and engaged in academic discussions that have helped me keep on top of research conducted here at Hopkins and abroad.”

Siebel scholar Garrett Jenkinson learning wet lab skills during INBT’s nanobio bootcamp. Photo by Mary Spiro.

Mathematics is the tool that W. Garrett Jenkinson uses in his research in the Complex Systems Science Laboratory of John Goutsias, professor of electrical and computer engineering. Jenkinson’s work can be applied to such real-life problems as how infections spread through a population via social interaction or how processes occur inside the cell, both of which can help inform the development of drugs to fight disease.

“The Complex Systems Science Laboratory takes the INBT spirit of interdisciplinary research to heart. The lab focuses on rigorous mathematical formulations that will simultaneously advance as many branches of science and engineering as possible,” Jenkinson said. “My graduate work has allowed me to follow my mathematical interests toward whatever application they might lead. In my tenure at Hopkins, I have published papers on a diverse array of topics including biochemical reaction networks, epidemiology, neurobiology, ecology, thermodynamics, unmanned automated vehicles, evolutionary game theory, pharmacokinetics, and social networks.

Through the IGERT program, Jenkinson said, INBT “trained me in fields that an electrical and computer engineer might otherwise find foreign, such as biology, nanotechnology, and wet lab techniques. Furthermore, the INBT has fostered relationships with my peers from diverse scientific backgrounds, with whom I have collaborated on multiple occasions to lend or receive advice in scientific matters that required expertise in multiple fields. I am excited to be joining the Siebel Scholars program which facilitates relationships across universities in the same way the INBT fosters these relationships across departments at Johns Hopkins University.”

Siebel scholar Yi Zhang. Photo by Mary Spiro.

Yi Zhang conducts his research in the lab of Jeff Tza-Huei Wang, an associate professor of mechanical engineering, biomedical engineering and oncology and also a project leader in the Center of Cancer Nanotechnology Excellence. Zhang’s work developing micro- and nanoscale molecular techniques to help diagnose cancer and infectious diseases has supported one of the core research goals of the CCNE. He is listed as an inventor on four patent applications, one of which has been licensed by a biotechnology company.

Said Zhang, “Being associated with an INBT affiliated laboratory offers me ample opportunities to collaborate with researchers in various fields and get help from my fellow students. Biomedical engineering is multidisciplinary in nature. My research focuses on bridging the gap between medical science and engineering, and my thesis is committed to improving molecular diagnostics using advanced nanotechnology. An integrated center like CCNE presents a new research paradigm by bringing together all necessary expertise from various fields to tackle one big problem in an extremely efficient way. It has definitely changed my view of conducting translational research.”

According to the organization’s website, Siebel Scholars and are chosen by the dean of their respective schools on the basis of outstanding academic achievement and demonstrated leadership. On average, Siebel Scholars rank in the top 5 percent of their class, many within the top 1 percent. The merit-based program provides $35,000 to each student for use in his or her final year of graduate studies.

The Siebel Scholars program was established in 2000 by the Siebel Foundation through a grant of more than $45 million to Carnegie Mellon University; Harvard University; The Johns Hopkins University; Massachusetts Institute of Technology; Northwestern University; Stanford University; Tsinghua University; University of California, Berkeley; University of California, San Diego; University of Chicago; University of Illinois at Urbana-Champaign; and University of Pennsylvania. Each year, five graduate students from each of the 17 partner institutions are honored as Siebel Scholars and receive a $35,000 award for their final year of studies.

Established in 2006, the Institute for NanoBioTechnology at Johns Hopkins brings together 223 researchers from every division of the University to create new knowledge and new technologies at the interface of nanoscience and medicine.

 

Engineered hydrogel helps grow new, scar-free skin

In early testing, this hydrogel, developed by Johns Hopkins researchers, helped improve healing in third-degree burns. Photo by Will Kirk/HomewoodPhoto.jhu.edu

Johns Hopkins researchers have developed a jelly-like material and wound treatment method that, in early experiments on skin damaged by severe burns, appeared to regenerate healthy, scar-free tissue.

In the Dec. 12-16 online Early Edition of Proceedings of the National Academy of Sciences, the researchers reported their promising results from mouse tissue tests. The new treatment has not yet been tested on human patients. But the researchers say the procedure, which promotes the formation of new blood vessels and skin, including hair follicles, could lead to greatly improved healing for injured soldiers, home fire victims and other people with third-degree burns.

The treatment involved a simple wound dressing that included a specially designed hydrogel—a water-based, three-dimensional framework of polymers. This material was developed by researchers at Johns Hopkins’ Whiting School of Engineering, working with clinicians at the Johns Hopkins Bayview Medical Center Burn Center and the Department of Pathology at the university’s School of Medicine.

Third-degree burns typically destroy the top layers of skin down to the muscle. They require complex medical care and leave behind ugly scarring. But in the journal article, the Johns Hopkins team reported that their hydrogel method yielded better results. “This treatment promoted the development of new blood vessels and the regeneration of complex layers of skin, including hair follicles and the glands that produce skin oil,” said Sharon Gerecht, an assistant professor of chemical and biomolecular engineering who was principal investigator on the study.

Guoming Sun, left, a postdoctoral fellow, and Sharon Gerecht, an assistant professor of chemical and biomolecular engineering, helped develop a hydrogel that improved burn healing in early experiments. Photo by Will Kirk/HomewoodPhoto.jhu.edu

Gerecht said the hydrogel could form the basis of an inexpensive burn wound treatment that works better than currently available clinical therapies, adding that it would be easy to manufacture on a large scale. Gerecht suggested that because the hydrogel contains no drugs or biological components to make it work, the Food and Drug Administration would most likely classify it as a device. Further animal testing is planned before trials on human patients begin. But Gerecht said, “It could be approved for clinical use after just a few years of testing.”

John Harmon, a professor of surgery at the Johns Hopkins School of Medicine and director of surgical research at Bayview, described the mouse study results as “absolutely remarkable. We got complete skin regeneration, which never happens in typical burn wound treatment.”

If the treatment succeeds in human patients, it could address a serious form of injury. Harmon, a coauthor of the PNAS journal article, pointed out that 100,000 third-degree burns are treated in U. S. burn centers like Bayview every year. A burn wound dressing using the new hydrogel could have enormous potential for use in applications beyond common burns, including treatment of diabetic patients with foot ulcers, Harmon said.

Guoming Sun, Gerecht’s Maryland Stem Cell Research Postdoctoral Fellow and lead author on the paper, has been working with these hydrogels for the last three years, developing ways to improve the growth of blood vessels, a process called angiogenesis. “Our goal was to induce the growth of functional new blood vessels within the hydrogel to treat wounds and ischemic disease, which reduces blood flow to organs like the heart,” Sun said. “These tests on burn injuries just proved its potential.”

Gerecht says the hydrogel is constructed in such a way that it allows tissue regeneration and blood vessel formation to occur very quickly. “Inflammatory cells are able to easily penetrate and degrade the hydrogel, enabling blood vessels to fill in and support wound healing and the growth of new tissue,” she said. For burns, the faster this process occurs, Gerecht added, the less there is a chance for scarring.

Originally, her team intended to load the gel with stem cells and infuse it with growth factors to trigger and direct the tissue development. Instead, they tested the gel alone. “We were surprised to see such complete regeneration in the absence of any added biological signals,” Gerecht said.

Sun added, “Complete skin regeneration is desired for various wound injuries. With further fine-tuning of these kinds of biomaterial frameworks, we may restore normal skin structures for other injuries such as skin ulcers.”

Gerecht and Harmon say they don’t fully understand how the hydrogel dressing is working. After it is applied, the tissue progresses through the various stages of wound repair, Gerecht said. After 21 days, the gel has been harmlessly absorbed, and the tissue continues to return to the appearance of normal skin.

The hydrogel is mainly made of water with dissolved dextran—a polysaccharide (sugar molecule chains). “It also could be that the physical structure of the hydrogel guides the repair,” Gerecht said. Harmon speculates that the hydrogel may recruit circulating bone marrow stem cells in the bloodstream. Stem cells are special cells that can grow into practically any sort of tissue if provided with the right chemical cue. “It’s possible the gel is somehow signaling the stem cells to become new skin and blood vessels,” Harmon said.

Additional co-authors of the study included Charles Steenbergen, a professor in the Department of Pathology; Karen Fox-Talbot, a senior research specialist from the Johns Hopkins School of Medicine; and physician researchers Xianjie Zhang, Raul Sebastian and Maura Reinblatt from the Department of Surgery and Hendrix Burn and Wound Lab. From the Whiting School’s Department of Chemical and Biomolecular Engineering, other co-authors were doctoral students Yu-I (Tom) Shen and Laura Dickinson, who is a Johns Hopkins Institute for NanoBioTechnology (INBT) National Science Foundation IGERT fellow. Gerecht is an affiliated faculty member of INBT.

The work was funded in part by the Maryland Stem Cell Research Fund Exploratory Grant and Postdoctoral Fellowship and the National Institutes of Health.

The Johns Hopkins Technology Transfer staff has filed a provisional patent application to protect the intellectual property involved in this project.

Related links:

Sharon Gerecht’s Lab

Johns Hopkins Burn Center

Johns Hopkins Institute for NanoBioTechnology

 

Story by Mary Spiro

Heart scar tissue may take active role in promoting deadly arrhythmias

Susan Thompson, PhD student in biomedical engineering, and Craig Copeland, PhD student in physics and astronomy, observe a single non-beating heart cell called a myofibroblast growing on a micropost device. (Photo Jay VanRensselaer)

Johns Hopkins University biomedical engineers and physicists affiliated with the Institute for NanoBioTechnology have completed a study that suggests that mechanical forces exerted by cells that build scar tissue following a heart attack may later disrupt rhythms of beating heart cells and trigger deadly arrhythmias. Their findings, published in a recent issue of the journal Circulation, could result in a new target for heart disease therapies.

Principal investigator Leslie Tung, a School of Medicine professor in the department of biomedical engineering, led a team that looked at how heart cells that beat (called “cardiomyocytes”) were affected by the non-beating cells (called “myofibroblasts”). Myofibroblasts are called to arms at the site of injury following a heart attack.

“The role of the myofibroblast (non-beating cells) is to make the injured area as small as possible. Through contraction, the myofibroblasts close the wound and lay down a protein matrix to reduce the scar area,” said lead investigator Susan Thompson, a pre-doctoral fellow in Tung’s Cardiac Bioelectric Systems Laboratory. “In doing so, the myofibroblasts pull on the membranes of adjacent cardiomyocytes. We found that these forces were strong enough to decrease the electrical activity of the working heart cells through mechanical coupling.”

Thompson electrically stimulated cultures containing both the beating and non-beating cells growing together, and found that when the electrical impulses occurred, the non-beating myofibroblasts pulled on the membranes of beating cardiomyocytes and disturbed their electrical rhythm. Before this study, scientists were aware that myofibroblasts influenced the function of cardiomyocytes by depositing scar tissue, which produces regions of poor or no conductivity in healing cardiac tissue. But the “pulling” scenario described by Tung’s group indicates that myofibroblasts play a more active role than previously realized, Thompson said.

Biomedical engineering professor Leslie Tung collaborated with physics professor Daniel Reich to understand how heart scar tissue actively contributes to deadly arrhythmias. (Photo by Jay VanRensselaer)

In fact, images created using a voltage-sensitive dye showed that the spread of electrical waves was greatly impaired in the cultures with the most non-beating cells. Electrical conduction improved significantly, however, when drugs were added that inhibited contraction or that blocked so called “mechano-sensitive” channels.

“This is a truly exciting discovery because it radically affects our way of thinking about how cardiac arrhythmias might arise,” Tung said.

Tung and Thompson wanted to find out how strong the forces exerted by the myofibroblasts were and whether they changed when certain drugs were added. So they turned for answers to Daniel Reich, professor and chair of the Henry A. Rowland Department of Physics and Astronomy in the Krieger School of Arts and Sciences, and his pre-doctoral student Craig Copeland.

To measure the strength of the contractile forces of the myofibroblasts, the team used a device made up of a platform comprising an array of flexible “microposts.” The array resembled a carpet with widely spaced fibers upon which single cells can grow. As the cells responded to their environment, they pulled on the posts. How much the posts bent provided data about the direction and strength of forces exerted. Single layers of myofibroblasts were grown on the micropost device and tested in the presence of the same compounds Thompson used in her conductivity experiments.

“Imagine gripping a basketball with one hand, palm facing downward,” Copeland said. “The forces you apply to the ball with your fingertips to keep it suspended are similar to the forces cells exert on their environment. If you were to place your hand on a bed of rubber nails and apply the same gripping force with your fingertips as you did with the basketball, the nails would bend and their tips be deflected. This is exactly what happens with cells cultured on the post arrays.”

Thompson also explained that scientists previously thought that non-beating cells affected the beating cells simply through openings called “gap junctions,” where the two cells came into physical contact. The greater electrical charge of the myofibroblasts would flow passively downhill through the gap junctions toward the cardiomyocytes and disrupt their rhythms.

Photo by Jay VanRensselaer

The group’s new hypothesis suggests another type of membrane channel opened by physical force—the mechano-sensitive channels—may be more important in regulating electrical activity of the cardiomyocytes than mere junctions connecting membranes.

The results of both the conductivity and the micropost experiments fully support this new hypothesis, the team said. Although they acknowledge that both the passive gap channels and the active pulling forces can explain how myofibroblasts affect the electrical activity of cardiomyocytes, the researchers believe the pulling forces could be more relevant to the development of deadly arrhythmias.

“We are not ruling out the current theory,” Thompson said. “But we are saying there is something else we should be looking at, and we think the pulling forces are a major component. This could provide another lane of therapeutic investigation, especially if drugs could be targeted specifically to the contraction of the myofibroblasts.”

The next step in the project will be to combine the micropost device with electrical experiments on cultures containing cardiomyocyte and myofibroblast cell pairs.

“Although technically quite challenging, it will allow us to unravel how pulling forces applied by the myofibroblast to the cardiomyocyte affects the cardiomyocyte’s electrical activity,” said Tung.

Both Tung and Reich are affiliated faculty members of Johns Hopkins Institute for NanoBioTechnology. Thompson and Copeland are INBT fellows in the institute’s Integrative Graduated Education and Research Traineeship (IGERT), funded by the National Science Foundation (NSF). The National Institutes of Health, American Heart Association and the NSF IGERT funded their work. Findings were published in the May 17, 2011 issue of the journal Circulation.

Story by Mary Spiro

Photos by Jay VanRenesselaer/Homewood Photography

INBT students to teach about self assembly during national science expo

USA Science and Engineering Festival, Oct 23-24

Predoctoral students, faculty and staff affiliated with INBT, including students in INBT’s National Science Foundation funded IGERT program, will help demonstrate the principles of self-assembly to children and adults alike. Participants at the INBT booth will be able to see at the macro scale what happens when materials of various shapes and sizes assemble into more complex structures at the nanoscale. Through a variety of hands-on experiments and by watching a variety of movies and animations about self assembly produced by the INBT Animation Studio, the students hope to be able to share their expertise in science and engineering with the general public.

During the two-day expo, USA Science and Engineering Festival organizers anticipate at least 750 exhibits from more than 350 of the nation’s leading science and engineering organizations including colleges and universities, corporations, federal agencies, museums and science centers, and professional engineering and science societies. Topics represented range from aerospace, green energy, medicine, biotechnology, climatology to robotics, nanotechnology, botany, neuroscience, genetics, and more.

The USA Science & Engineering Festival is the result of the highly successful inaugural San Diego Science FestivalSM held in April 2009 and both are the brainchild of life science and high technology entrepreneur Larry Bock. The festival is hosted by Lockheed Martin and sponsors include Life Technologies Foundation, Clean Technology and Sustainability Industries Organization (CTSI), Larry and Diane Bock, ResMed Foundation, Farrell Family Foundation, Alexandria Real Estate Equities, Northrop Grumman Corporation, Agilent Technologies, Amgen, Celgene Corporation, The Dow Chemical Company, National Institutes of Health, Illumina, You Can Do the Rubik’s Cube, Vertex Pharmaceuticals Inc., Genentech Inc., MedImmune, Sandia National Laboratories, Project Lead The Way (PLTW), K&L Gates, NuVasive Inc., FEI Company, Case Western Reserve University, Silicon Valley Bank, Bechtel Corporation, SpaceX and the National Radio Astronomy Observatory. Media partners include Popular Science and Science Illustrated, New Scientist, EE Times Group, SCIENTIFIC AMERICAN, POPULAR MECHANICS, Forbes Wolfe Emerging Tech Report, FAMILY Magazine and SciVee, Inc.

Additional Information:

Preview of the types of exhibits planned for the National Expo and view a short video of what happened in San Diego here.

For a complete list of sponsors, partners and exhibitors, click here.

INBT Presents Professional Development Seminars

Johns Hopkins Institute for NanoBioTechnology (INBT) will host four professional development seminars for scientists and engineers this summer. These seminars aim to expand student’s knowledge of issues and ideas relevant to but outside of the laboratory and classroom experience. Topics this summer will include intellectual property, science journalism, and more. Talks will be held June 10, June 24, July 8, and July 22 at 11 a.m. in Maryland Hall 110. Please RSVP to Ashanti Edwards, aedwards@jhu.edu to attend.

NEXT UP

Charles Day, second speaker at the 2009 INBT Professional Development Seminars

Charles Day, second speaker at the 2009 INBT Professional Development Seminars.

June 24:

“From tip to tale: How science news is made“

Charles Day, senior editor Physics Today

Day earned a PhD in astronomy from the University of Cambridge. After a postdoctoral position at Japan’s Institute of Space and Astronautical Science, he worked for six years at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. He now writes for and edits the Search and Discovery Department for Physics Today, the flagship publication of The American Institute of Physics and most influential and closely followed physics magazine in the world.

July speakers to be announced. Check back here for more info.

Past speakers:

June 10:

“The Role of Intellectual Property in Technology Commercialization and Academic Research.”

John N. Fini, director of intellectual property, Krieger School of Arts and Sciences, Whiting School of Engineering

Fini brings a wealth of experience in technology transfer and technology commercialization and in the entrepreneurial environment. He works closely with Johns Hopkins Technology Transfer with the aim of promoting the Homewood campus as a technology powerhouse.