Johns Hopkins Institute for NanoBioTechnology hosts its annual Science and Engineering Film fest on Wednesday, July 20 at 11 a.m. to noon in the Arellano Theater in Levering Hall on the Homewood Campus. Films were created this summer by graduate students in INBT’s course on Communication for Scientists and Engineers and will showcase current research happening in institute affiliated laboratories. Three films will be shown and the students who made them will be available for questions after each one. The event is free and open to the public.
Several researchers associated with Johns Hopkins Institute for NanoBioTechnology have received grants from the Maryland Stem Cell fund.
In the Whiting School of Engineering, awardees include Sharon Gerecht, Kent Gordon Croft Investment Management Faculty Scholar in the Whiting School of Engineering’s Department of Chemical and Biomolecular Engineering and associate director of the Institute for NanoBioTechnology, and Warren Grayson, associate professor in the Department of Biomedical Engineering. Both received MSCRF Investigator Initiated Grants. Gerecht’s stem cell project targets diabetic wound treatment, and Grayson’s targets volumetric muscle loss.
In addition, Dhruv Vig, a post-doctoral student in INBT and the Department of Mechanical Engineering, received one of the organization’s Post-Doctoral Fellowship Grants for his project “Geometric Cues in the Establishment and Maintenance of Heterogeneous Stem Cell Colonies.”
According to Vig, the goal of this investigation is to introduce a new way of characterizing the potency and/or differentiation of human pluripotent stem cells.
“Our work uses an innovative blend of mathematical modeling and experimental approaches to shed light on the role of physical forces and geometric constraint involved in the establishment and maintenance of proper stem cell functions,” explains Vig, who is advised by Gerecht and Sean Sun, professor and vice-chair in the Department of Mechanical Engineering.
Other INBT affiliated faculty members who received the grants include Guo-li Ming, M.D., Ph.D., targeting schizophrenia and autism and Michael McMahon, Ph.D., targeting intervertebral disc degeneration, both from the Johns Hopkins School of Medicine.
Of the 26 MSCRP grants, 21 went to Hopkins-affiliated researchers. The purpose of these grants and fellowships is to promote state-funded stem cell research.
As a service to the university community, Johns Hopkins Institute for NanoBioTechnology offers seminars with guest speakers on topics relevant to nanotechnology, medicine and engineering. All seminars will take place on select Tuesdays in Croft G40 at 2 p.m. Space is limited, so please RSVP to Camille Bryant at email@example.com. Schedule and locations are subject to change. Get a printable flyer here.
- June 7
Polycystins: sensors and orchestrators at the crossroad of epithelial growth and differentiation
Dr. Rong Li
- June 21
Technology transfer and licensing for researchers
Ms. Emily Williams
- July 12
Dissecting the role of matrix mechanics in the Tumor Ecosystem
Dr. Kandice Tanner
- July 28
Photonics solutions to complex problems in cancer research, nanoparticle drug delivery, and medical diagnosis
Dr. Ishan Barman
- August 23
Multi-modal diagnostics and treatment of cancer using paramagnetic nanoparticles
Dr. Israel Gannot
JHU, Tel Aviv University
Like a bicycle messenger weaving through busy city streets, cancer cells are skilled at maneuvering through microenvironments. Researchers know they use complex signalling 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.
Konstantopoulos, 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 firstname.lastname@example.org
You know what’s funny?
If you were to have asked me during my senior year of high school what Materials Science and Engineering (MSE) was, I wouldn’t have the slightest clue how to answer. Now, less than five years later, I’m sitting here writing this as a first-year MSE PhD student, and were I to be asked that question now, I could go on for hours about how it is one of the coolest, most interdisciplinary fields anyone could get themselves into.
MSE is often an overlooked discipline due to it not being a “major” (read: Mechanical, Chemical, Electrical) engineering discipline. What most people don’t realize, however, is that practically everything you do and take advantage of on a day-to-day basis, you have a materials engineer to thank for. That iPhone of yours you stare at for over an hour a day? It’s a materials masterpiece.
Consider how many times you’ve accidentally dropped your phone (whether it be on the ground or on your face while you’re laying in bed) without the screen cracking. You have the engineers at Corning to thank for that. Corning’s Gorilla Glass is no ordinary day-to-day window glass; it’s a special aluminosilicate glass that has undergone a process called ion exchange. Basically, what happens is you dip a sodium-containing glass into a hot bath of potassium ions, where a literal exchange happens between the sodium and the potassium atoms. Since potassium is ever so slightly larger than sodium, the glass is put under compression. If anyone wants to break this glass, they must first overcome the genius behind its reinforcement. You can read more about how gorilla glass is made [here].
The materials genius behind the iPhone isn’t limited to just its screen. The production of the hardware that makes your phone so fast was also a materials problem—getting those two billion transistors to fit on a chip inside your iPhone took literal decades of work.
Problems like these are what brought me to take on MSE as my undergraduate major, but the interdisciplinary nature of the field is what convinced me to stay.
My “Intro to MSE” professor (and my eventual undergraduate research advisor), Dr. Laura Fabris, would often tell us about her research. She worked on the production of gold nanoparticles (?!) that could be used for disease/biological marker detection. Her research fascinated me, and was what originally got me interested in the region where materials and biology overlap. The more that I read about what was being done, the more I longed to be a part of it. These desires have brought me to the Johns Hopkins University for my graduate studies, and ultimately the Institute for NanoBioTechnology so that I could gain further insight and training on what is being done at the forefront of my field.
Now that I’m here at Hopkins, I’ve found myself working on the synthesis and self-assembly of polymeric nanoparticles used for biomedical applications. Did you know that most drugs on the market that are used for treatment of diseases such as cancer are hydrophobic? Now, consider the fact that your body is about 60% water… This makes delivering drugs to certain areas of your body a huge problem, and has posed a challenge for hundreds of scientists and engineers. Using the polymeric nanoparticles my lab synthesizes, we can store these drugs in a safe “vehicle” so that they may safely arrive wherever they are needed. Cool, huh?
With that, I’d like to leave you with the video from Corning that truly was the tipping point to my choosing MSE. Although it no longer lines up with the direction I’m taking myself, it shows how the future lies in the hands of engineers who believe in the power of materials, and I hope I have inspired you to consider the impact materials make in both our everyday lives and the (not-so-distant) future.
Lazaro Pacheco is a first year PhD student in the Materials Science and Engineering department at the Johns Hopkins University. He is a member of the Herrera Lab, and he is currently working on measuring the polydispersity of polymer chains that are ‘grafted from’ a central polymeric backbone.
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Happy 10th Anniversary INBT! Johns Hopkins Institute for NanoBioTechnology was established on May 16, 2006 with funding from the National Institutes of Health and NASA. Over the last decade, we have achieved many exceptional accomplishments and attained significant research milestones. INBT has attracted nearly $70 million in research funding and added more than 250 affiliated faculty members from across many divisions and departments of the university. INBT has launched several spin-off research centers, such as the Physical Sciences Oncology Center and the Center for Cancer Nanotechnology Excellence. The Institute has also initiated nanobio-related training programs for students from pre-college through the postdoctoral level, such as the NanoBio Research Experience for Undergraduates and the International Research Experience for Students, in which participants travel to Belgium to conduct nanobio research in IMEC’s world-class research facility. Hundreds of students have completed these programs and our alumni hold outstanding positions within industry and academia. INBT also has developed strong corporate partnerships and continues to seek ways to move innovative research that solves the pressing problems in human health from the laboratory to the marketplace.
On April 21, INBT hosted an open house and anniversary celebration that attracted more than 100 people to its headquarters in Croft Hall on the Homewood campus of the Johns Hopkins University. We also invited visitors to participate in 15 hands-on demonstrations developed by labs located in the building.
Thanks to everyone who helped celebrate with us on that day and to those who continue to support us every day as INBT furthers its mission as a hub for innovative multidisciplinary research. Click below to view a sideshow of photos from our open house. Photos by INBT staff members Jon French and Mary Spiro.
The world of physics covers a wide range of length scale: from nanometer scale atoms all the way up to stars and galaxies. When speaking of physics, people tend to think of things that are not “alive”, such as material physics, particle physics, astronomy, etc.
In the last decade, a new area of physics called active matter physics has arisen. To better understand active matter physics, it is helpful to introduce a similar field, soft matter physics. Soft matter physics mainly studies the group behavior of particles with the size of several micrometers. Behavior of a system at such a small size is largely determined by thermal dynamics. Glass, soft gels, granular material are all studied by soft matter physics.
Active matter physics, on the other hand, is very similar to soft matter physics, since it also mainly focuses on studying the group behavior of a system that arises from the interactions of “particles”. However, one of the crucial differences between active matter physics and soft matter physics is that active matter physics studies particles that are “active”, which means that by consuming energies from the environment, they can produce self-motility. Systems studied by active matter physics can range from bird flocks (Fig.1) to cytoskeleton structures inside cells (Fig.2).
Studying active matter physics provides another perspective for understanding the emerging behavior in a biological system. For instance, there has been work done on simulating cell motion in densely packed tissues. Physicists using tools from statistical mechanics have successfully simulated how cells move around inside tissues and have found that there is a transition where cell motility changes from liquid-like flowing into solid-like jiggling around its initial position. They are able to plot out the phase diagram of such transitions in a space determined by three parameters: cell moving speed, persistence time along a single cell track, and a shape index that characterizes the competition between cell-cell adhesion and cortical tension. Such results provide an insight into the understanding of similar solid-to-liquid transition observed in cancer progressions.
About the author: Yu Shi is a 4th year PhD student in the Department of Physics & Astronomy at Johns Hopkins University. He is in Prof. Daniel Reich’s lab, and his current works focus on studying dynamic properties of actin-myosin system inside cells using micro-patterned substrate.
1. Dapeng Bi, X. Yang, M. C. Marchetti, M. L. Manning, “Motility-driven glass transitions in biological tissues,” Phys. Rev X, arXiv:1509.06578 (2015).
2. M.C. Marchetti, J.F. Joanny, S. Ramaswamy , T.B. Liverpool, J. Prost, Madan Rao, and R. Aditi Simha,” arXiv:1207.2929v1 (2012)
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Charles M. Lieber of Harvard University will present the 71st Remsen Lecture, Thursday, May 12 at 6 p.m. in 101 Remsen Hall. He will deliver the talk “Nanoelectronic Tools for Brain Science” and will receive the Remsen Award from the Maryland section of the American Chemical Society. The event is free and open to the public. Light refreshments will be served at 5:30 in Room 140 and a reception will follow the lecture, also in Room 140.
Charles M. Lieber received his undergraduate degree in chemistry from Franklin and Marshall College and carried out his doctoral studies at Stanford University, followed by postdoctoral research at the California Institute of Technology. In 1987 he assumed an Assistant Professor position at Columbia University, embarking on a new research program addressing the synthesis and properties of low-dimensional materials. He moved to Harvard University in 1991 and now holds a joint appointment in the Department of Chemistry and Chemical Biology, as the Mark Hyman Professor of Chemistry, and the Harvard John A. Paulson School of Engineering and Applied Sciences.
He serves as the Chair of the Department of Chemistry and Chemical Biology. At Harvard, Lieber has pioneered the synthesis of a broad range of nanoscale materials, the characterization of the unique physical properties of these materials and the development of methods of hierarchical assembly of nanoscale wires, together with the demonstration of applications of these materials in nanoelectronics, nanophotonics, and nanocomputing, as well as pioneering the field of nano-bioelectronics where he has made seminal contributions to biological and chemical sensing, the development of novel nanoelectronic cell probes, and cyborg tissues.
Lieber’s work has been recognized by a number of awards, including the first ever Nano Research Award, Tsinghua University Press/Springer (2013); IEEE Nanotechnology Pioneer Award (2013); Willard Gibbs Medal (2013); Wolf Prize in Chemistry (2012); ACS Inorganic Nanoscience Award (2009); NBIC Research Excellence Award, University of Pennsylvania (2007); Nanotech Briefs Nano 50 Award (2005); ACS Award in the Chemistry of Materials (2004); World Technology Award in Materials (2004 and 2003); Scientific American 50 Award in Nanotechnology and Molecular Electronics (2003); APS McGroddy Prize for New Materials (2003); MRS Medal (2002); Feynman Prize in Nanotechnology (2001); NSF Creativity Award (1996); and ACS Award in Pure Chemistry (1992).
Lieber is an elected member of the National Academy of Sciences, the American Academy of Arts and Sciences and the National Academy of Inventors, and Fellow of the American Chemical Society, Materials Research Society, and American Physical Society. He is Co-Editor of Nano Letters and serves on the Editorial and Advisory Boards of a large number of science and technology journals. Lieber also serves on the Technical Advisory Committee of Samsung Electronics. He has published over 380 papers and is the principal inventor on 40 patents. In his spare time, Lieber has been active in commercializing nanotechnology, and founded the nanotechnology company Nanosys, Inc. in 2001 and the nanosensor company Vista Therapeutics in 2007, and nucleated Nantero, Inc. from his laboratory in 2001.
A Johns Hopkins biomedical engineer at the School of Medicine has found that a blend of natural and man-made materials works best to create a better bone replacement with 3D printing technology. Warren Grayson, an affiliated member of Johns Hopkins Institute for NanoBioTechnology, reports his findings in the journal ACS Biomaterials Science and Engineering.
Read more below.
To make a good framework for filling in missing bone, mix at least 30 percent pulverized natural bone with some special man-made plastic and create the needed shape with a 3-D printer. That’s the recipe for success reported by researchers at The Johns Hopkins University in a paper published April 18 online in ACS Biomaterials Science & Engineering.
Each year, the Johns Hopkins scientists say, birth defects, trauma or surgery leave an estimated 200,000 people in need of replacement bones in the head or face. Historically, the best treatment required surgeons to remove part of a patient’s fibula (a leg bone that doesn’t bear much weight), cut it into the general shape needed and implant it in the right location. But, according toWarren Grayson, Ph.D., associate professor of biomedical engineering at the Johns Hopkins University School of Medicine and the report’s senior author, the procedure not only creates leg trauma but also falls short because the relatively straight fibula can’t be shaped to fit the subtle curves of the face very well.
That has led investigators to 3-D printing, or so-called additive manufacturing, which creates three-dimensional objects from a digital computer file by piling on successive, ultrathin layers of materials. The process excels at making extremely precise structures — including anatomically accurate ones — from plastic, but “cells placed on plastic scaffolds need some instructional cues to become bone cells,” says Grayson. “The ideal scaffold is another piece of bone, but natural bones can’t usually be reshaped very precisely.”
In their experiments, Grayson and his team set out to make a composite material that would combine the strength and printability of plastic with the biological “information” contained in natural bone.
They began with polycaprolactone, or PCL, a biodegradable polyester used in making polyurethane that has been approved by the FDA for other clinical uses. “PCL melts at 80 to 100 degrees Celsius (176 to 212 Fahrenheit) — a lot lower than most plastics — so it’s a good one to mix with biological materials that can be damaged at higher temperatures,” says Ethan Nyberg, a graduate student on Grayson’s team.
PCL is also quite strong, but the team knew from previous studies that it doesn’t support the formation of new bone well. So they mixed it with increasing amounts of “bone powder,” made by pulverizing the porous bone inside cow knees after stripping it of cells.
“Bone powder contains structural proteins native to the body plus pro-bone growth factors that help immature stem cells mature into bone cells,” Grayson says. “It also adds roughness to the PCL, which helps the cells grip and reinforces the message of the growth factors.”
The first test for the composite materials was printability, Grayson says. Five, 30 and 70 percent bone powder blends performed well, but 85 percent bone powder had too little PCL “glue” to maintain clear lattice shapes and was dropped from future experiments. “It was like a chocolate chip cookie with too many chocolate chips,” Nyberg says.
To find out whether the scaffolds encourage bone formation, the researchers added human fat-derived stem cells taken during a liposuction procedure to scaffolds immersed in a nutritional broth lacking pro-bone ingredients.
After three weeks, cells grown on 70 percent bone powder scaffolds showed gene activity hundreds of times higher in three genes indicative of bone formation, compared to cells grown on pure PCL scaffolds. Cells on 30 percent bone powder scaffolds showed large but less impressive increases in the same genes.
After the scientists added the key ingredient beta-glycerophosphate to the cells’ broth to enable their enzymes to deposit calcium, the primary mineral in bone, the cells on 30 percent scaffolds produced about 30 percent more calcium per cell, while those on 70 percent scaffolds produced more than twice as much calcium per cell, compared to those on pure PCL scaffolds.
Finally, the team tested their scaffolds in mice with relatively large holes in their skull bones made experimentally. Without intervention, the bone wounds were too large to heal. Mice that got scaffold implants laden with stem cells had new bone growth within the hole over the 12 weeks of the experiment. And CT scans showed that at least 50 percent more bone grew in scaffolds containing 30 or 70 percent bone powder, compared to those with pure PCL.
“In the broth experiments, the 70 percent scaffold encouraged bone formation much better than the 30 percent scaffold,” says Grayson, “but the 30 percent scaffold is stronger. Since there wasn’t a difference between the two scaffolds in healing the mouse skulls, we are investigating further to figure out which blend is best overall.”
Although the use of “decellularized” cow bone has been FDA-approved for clinical use, in future studies, the researchers say, they hope to test bone powder made from human bone since it is more widely used clinically. They also want to experiment with the designs of the scaffolds’ interior to make it less geometric and more natural. And they plan to test additives that encourage new blood vessels to infiltrate the scaffolds, which will be necessary for thicker bone implants to survive.
Other authors of the report include Ben Hung, Bilal Naved, Miguel Dias, Christina Holmes, Jennifer Elisseeff and Amir Dorafshar of the Johns Hopkins University School of Medicine.
This work was supported by the National Institute of Dental and Craniofacial Research (F31 DE024922), the Russell Military Scholar Award, the Department of Defense, the Maryland Stem Cell Research Fund and the American Maxillofacial Surgery Society Research Grant Award.
Press release by Catherine Gara; 443-287-2251; email@example.com and Shawna Williams; 410-955-8236; firstname.lastname@example.org.
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Pharos Biologicals, LLC (Pharos) has been awarded the exclusive worldwide licenses for a patented Lysosome-Associated Membrane Protein (LAMP) DNA vaccine technology, as well as for certain nanotechnologies to deliver the vaccines, by Johns Hopkins University School of Medicine. The worldwide licenses are for use in the development and delivery of vaccines for influenza and flaviviruses.
Pharos was formed in December 2015 by J. Thomas August, M.D., University Distinguished Service Professor of Pharmacology and Molecular Sciences and Oncology at the Johns Hopkins University School of Medicine and the Johns Hopkins Institute for NanoBioTechnology. The initial focus of the company is on the Zika vaccine development, to be followed by vaccines for dengue and influenza viruses. The company anticipates that it will be ready to begin Phase 1 clinical trials of its Zika vaccine candidate by autumn of 2016.
The Baltimore Sun has reported the news here.
The LAMP technology was validated commercially in October 2015 when a license awarded by Johns Hopkins to Immunomic Therapeutics, Inc. for allergen vaccines was sold to Astellas, a global pharmaceutical company, for $300 million.
The LAMP technology, invented by Dr. August, represents a breakthrough in the application of DNA vaccines by the use of normal cellular mechanisms to enhance the immune response to the vaccine. Most vaccines use a weakened form of a pathogen in which a live, but reduced virulence version of the virus is introduced into the body. The LAMP DNA vaccine is not a live virus vaccine, has a more rapid development timeline, delivers the pathogen antigen directly to cell proteins that bring about immunological responses, and is highly stable.
The threat that Zika virus poses is growing, with the WHO declaring a state of Public Health Emergency of International Concernon February 1, 2016, and it is expected that travel-associated cases will increase (http://www.cdc.gov/zika/geo/). The virus can also be spread by sexual transmission, which potentially raises the risk of spread.
Pharos is also supported by research directed by Prof. Hai-Quan Mao PhD in Department of Materials Science and Engineering at the Whiting School of Engineering, and the Translational Tissue Engineering Center at the Johns Hopkins School of Medicine, and an Associate Director of the Institute for NanoBioTechnology at Johns Hopkins University. Dr. Mao was the 2015 winner of the Cohen Translational Engineering Award and the Louis B. Thalheimer Award for Translational Research.
David W. Wise, a business executive with sixteen years of C-Level experience and who has been active in the medtech startup and venture capital community in Baltimore as the Venture Advisor to the Abell Foundation for the past several years, serves as Chief Executive Officer of Pharos.
For more information on the LAMP Vaccine technology and Pharos Biologicals, visit PharosBiologicals.com.
To learn more about Johns Hopkins Institute for NanoBioTechnology, visit inbt.jhu.edu.
Written by Daniel Waldman for Pharos Biologicals.
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