Take a nanobreak at INBTea Time every Wednesday

Johns Hopkins Institute for NanoBioTechnology is pleased to announce the first INBTea Time every Wednesday in the corridor outside of our headquarters at 100 Croft Hall from 2:30 to 3 p.m. Grab a drink and a light snack. The first INBTea Time will be held on Wednesday, September 11. Enjoy a quick break and great conversation!

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Blog posts from Belgium


Catholic University of Leuven (Photo by Colin Paul)

During the summer, a select group of researchers from Johns Hopkins travel to Leuven, Belgium to work at the micro- and nano- electronics fabrication laboratories of IMEC. Usually three to five students are able to go over for up to three months to work on a research project that is collaboratively arranged by both IMEC researchers and Johns Hopkins University faculty.

The students usually are advancing some aspect of a project they have started here at JHU. In a few instances, researchers from IMEC come to JHU to work. Faculty at both locations work together to develop projects that are mutually beneficial to all parties.

Johns Hopkins Institute for NanoBioTechnology provides financial support for our research through the National Science Foundation’s International Research Experience for Students (IRES) program. The arrangement with IMEC has been in place since 2009.

IMEC, which used to be referred to as the Interuniversity Microelectronics Centre, is an unusual research entity that grew out of an agreement between the Flemish government and the academic community at Catholic University of Leuven They now have more than 2,000 researchers from all around the globe working at their high tech facility.

To keep in touch with our researchers while they are away and to find out about their outside of laboratory adventures, INBT established the IMEC blog.  Click here to check out what our students have done, this summer and over the last several years.


Are cellular technologies scalable?

Are cellular technologies scalable? According to Phillip Vanek, Head of Innovation at Lonza Bioscience, the answer to this question is “yes”, but only if scaling is considered very early in the technology’s development. Vanek addressed the topic of scalability at his talk at the INBT symposium.

scalabilityScaling-up of bench-top science into industrial processes is difficult for a number of reasons. Commercial-scale production of cell-based products introduces regulatory challenges and production volumes never encountered on the bench scale. Even the basic laboratory chore of cell passage can become a large hurdle when attempting to grow large number of cells in the multi-layered cell factory system.

With such challenges in mind, Vanek lays out a number of ways to improve the success rate of scaling up processes. He stressed that a process should ideally be closed for maximum success. A closed process prevents product contamination and minimizes user error. Also, maximizing automation helps minimize operator error in processing.

Most importantly, the treatable patient pool sizes and dosage requirements need to be well-known for a process to be commercially successful. Vanek concluded that cellular technologies are scalable, but only if researchers start with end goals in mind early and are well-aware of potential pitfalls.


Editor’s Note: This 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 Christian Pick, a doctoral candidate in the chemical and biomolecular engineering laboratory of Joelle Frechette. Look for other symposium summaries on the INBT blog.


Johns Hopkins opens mind-blowingly beautiful teaching labs

When I was an undergraduate at [insert state university name here] most of the biology and chemistry teaching labs we undergrads worked in were purely utilitarian spaces for bench work and all had seen better days. In fact, they looked more like my high school science labs.  My high school labs might have been nicer.

New Undergraduate Teaching Labs. (Photo by Mary Spiro)

New Undergraduate Teaching Labs. (Photo by Mary Spiro)

But there is no reason why even lower level science should not be taught in an aesthetically pleasing space. For some undergraduates, lower level science courses are a requirement that must be knocked off the graduation to-do list. Why not make the experience more exciting?

Johns Hopkins University has constructed 105,000 square feet of new undergraduate laboratory teaching space on the far side of Mudd and Levi Halls on the Homewood campus. The space beautifully integrates into the natural surroundings offered by the Buffano Sculpture Gardens. The open feel is extremely important, I think, because it allows so much natural like to come in  that it could make that time in lab section, which can seem never-ending, into something much more tolerable–even enjoyable.

Undergrads studying chemistry, biology, biophysics, neuroscience and psychological and brain sciences will be using the 20 labs that were created with the new space. The philosophy behind the design of the building is to encourage cross disciplinary collaboration, which as many know is something that Johns Hopkins Institute for NanoBioTechnology strives for in all of its endeavors. It is nice to see that same kind of sentiment carried out in a physical way in this new campus structure.

For now, the addition is just being called the UTL (undergraduate teaching laboratories) building. The core of the structure includes space for nuclear magnetic resonance imaging and tissue and cell culture. Lab space connects to the adjacent academic buildings via mingling areas, ample seating, faculty offices, a large biology research lab, a computer lab, seminar rooms, a coffee bar and more. 

I recommend walking over to the UTL yourself and having a look around if you are on the Homewood campus. If not you can watch this video. It will make you want to register for a chemistry class like a freshman. No, joke. This building is a work of art and an amazing addition to the already beautiful Homewood campus.

Read the story about the new laboratory building here.

Commercialization of nanotech no easy task

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 Christian Pick, a doctoral candidate in the chemical and biomolecular engineering laboratory of Joelle Frechette. Look for other symposium summaries on the INBT blog.

Govt-RegulationsOne of the greatest promises of merging nanotechnology with medicine is in the creation of highly selective vehicles for drug delivery based on nanoparticles. However, translating nanoparticles into commercialized medical products comes with many challenges. Anthony Tuesca, a scientist in the Innovative Drug Delivery Group at MedImmune, outlined a number of these challenges and ways to address them. 

Research in nanotechnology begins at the lab bench, often without much thought given to future commercialization. But commercialization is a huge undertaking. In between the lab-bench and final product there is a whole litany of challenges that must be tackled. One such challenge lies in scaling up processes for production. As Tuesca stated, for scale-up to be viable, laboratory processes must be compatible with current manufacturing capabilities.

Another challenge is navigating an often confusing regulatory landscape. Although nanoparticle based therapies don’t necessarily invoke harsher requirements than conventional medical treatments (in that both require clinical trials that demonstrate safety and efficacy) more complex technology requires more proof of effectiveness. Interestingly, Tuesca mentions that the U.S. Food and Drug Administration currently lacks an official definition of nanotechnology.

Ultimately, Tuesca’s presentation urges researchers to take a proactive role in translating laboratory discoveries into viable medical technology. Such a role requires researchers to consider future commercialization early in their research and act accordingly.

Did you know that the Johns Hopkins Center of Cancer Nanotechnology Excellence has a working group focused on commercialization? Read more about it here.


Unlocking the mysteries of the blood-brain barrier

It might astonish you to know that, although we use our brains all the time, science knows very little about how they actually work. That is why recently, President Barack Obama announced a $100 million initiative to map the human brain.

“We can identify galaxies light-years away; we can study particles smaller than an atom; but we still haven’t unlocked the mysteries of the three pounds of matter that sits between our ears,” Obama said in a press conference on the announcement April 2.

The blood-brain barrier involves functional interactions between endothelial cells that form brain capillaries, astrocytes, and pericytes in a complex microenvironment. (Illustration by Martin Rietveld)

The blood-brain barrier involves functional interactions between endothelial cells
that form brain capillaries, astrocytes, and pericytes in a complex microenvironment. (Illustration by Martin Rietveld)

Obama’s Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) project will seek to discover what occurs between the 100 billion cells firing inside the brain with the goalof helping to prevent and even cure neurological diseases, such as Alzheimer’s or Parkinson’s, that affect as many as 100 million Americans.

Johns Hopkins University is at the forefront of brain science research. The Brain Science Institute (BSi) at the Johns Hopkins School of Medicine was launched to develop new multidisciplinary research teams; create cutting edge-research cores for use by all brain researchers at Hopkins; and foster translation of discoveries to treatments of brain diseases, in part, by improving our ability to partner with industry and biotechnology.

In 2012, Peter Searson, professor of materials science and engineering and director of Johns Hopkins Institute for NanoBioTechnology (INBT), joined forces with Jeffrey Rothstein MD, PhD, director of the BSi, to create the Blood-Brain Barrier Working Group. This group brings together researchers with diverse interests and expertise to address key problems associated with drug delivery, to discover the role of the blood-brain barrier (BBB) in disease, and to elucidate the structure and function of the BBB.

“The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system and protects the central nervous system from potentially harmful chemicals while, at the same time, regulating transport of essential molecules and maintaining a stable environment,” Searson said. “It is formed from highly specialized endothelial cells that line the brain capillaries, which transduce signals in two directions: from the vascular system and from the brain. The structure and function of the BBB is dependent upon the complex interplay between different cell types, specifically the endothelial cells, astrocytes and pericytes, within the extracellular matrix of the brain and with the blood flow in the capillaries.”

Although the BBB serves the important purpose of tightly regulating the environment of the brain and preventing sudden changes, which the brain cannot tolerate, Searson said, “this interface also blocks the passage of drug molecules to treat disease, neurodegenerative disorders, inflammation or stroke. Unfortunately, animal models are insufficient for use in under-standing how the human blood-brain barrier functions or responds to drugs. In addition, little is known about how disease, inflammation or stroke disrupts or damages the blood-brain barrier.”

With this in mind, the BBB working group has two primary goals, Searson explained. “Our long-term goal is to build an artificial microvessel that will be the first platform that recapitulates a brain capillary in its local microenvironment. This will enable fundamental studies as well as drug discovery and the development of methods to cross the blood-brain barrier,” Searson said.

The second goal is to understand how the blood-brain barrier can be damaged or disrupted so that strategies can be developed to repair it. Injury and disease can disrupt the normal structure and function of the blood brain barrier.

Currently the BBB Working Group has 40 researchers from disciplines as diverse as anesthesiology, materials science and engineering, pharmacology and oncology. Three postdoctoral fellows and 12 pre-doctoral students are also involved. The group meets monthly and hosts expert speakers on various topics. The working group website also lists current funding opportunities to which members can apply and conferences and workshops of interest.

Membership in the working group is open to any student, faculty member or staff at Johns Hopkins University in any discipline.

Visit the Blood-Brain Barrier Working Group website here.

This article was written by Mary Spiro and appeared in the 2013 issue of Nano-Bio Magazine.

Recent publications from the PS-OC network

Human breast cancer cells. (Image created by Shyam Khatau/ Wirtz Lab)

Human breast cancer cells. (Image created by Shyam Khatau/ Wirtz Lab)

Johns Hopkins Physical Sciences-Oncology Center is part of a network of centers studying how physical forces affect the spread of cancer. Every quarter, the National Cancer Institute complies a list of recent publications from all the participating centers. So if you want to keep up with what the Johns Hopkins PS-OC and other groups have been up to on their quest to discover the physical science mechanisms behind metastasis, look no further than this list which you can download here.

Using the physicals sciences to study cancer offers a new approach over the “traditional” genetic means of studying the disease. To learn more about the unique philosophy behind the NCI’s PS-OC network of centers visit this link.

Nanotechnology for gene therapy

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.

One of the key features of nanotechnology is its wide range of applicability across multiple biological scenarios ranging from gene therapy to immune system modulation. Jordan Green, an assistant professor of Biomedical Engineering at Johns Hopkins University, summarized some of the fascinating applications of nanotechnology on which his laboratory has been working. Green is an INBT affiliated faculty member.

One of the Green lab projects involves the design and implementation of nanoparticle based vectors for delivery of genetic material to the cell. Green demonstrated how these particles could be used to deliver DNA and induce expression of a desired gene, or small interfering RNA (siRNA) to silence the expression of a target gene. These genetic therapeutics are being developed to target a wide variety of retinal diseases and cancers.

Jordan Green (Photo by Marty Katz)

Jordan Green (Photo by Marty Katz)


As opposed to viral based vectors for gene therapy, nonviral vectors such as nanoparticles are safer, more flexible in their range of cellular targets, and can carry larger cargoes than viruses, Green explained.


Another project in the Green lab involves the development of micro and nano dimensional artificial antigen presenting cells (aAPCs) for cancer immunotherapy. These aAPCs mimic the natural signals that killer T-cells receive when there is an invader (bacteria, virus, cancer cell, etc.) in the body. The Green lab is currently working with these particles to stimulate the immune system to fight melanoma.


Green Group

Taking a digital perspective on cancer

Editor’s Note: This story was written by Bryan Kohrs, a junior in Biophysics at Johns Hopkins University  with a strong interest in science writing and science. It first appeared in the 2013 issue of Nano-Bio Magazine.

Denis Wirtz lines up next to many other scientists in the war on cancer. But while others battle with familiar technologies and ideas, Wirtz has armed himself with a new imaging technology, a fresh strategy on how to better combat this dreaded disease and a five year grant from the National Cancer Institute (NCI).

Wirtz, a professor of Chemical and Biomolecular Engineering at Johns Hopkins, is carving out a niche for himself in cancer research by focusing on the look and physical structure of cancerous cells rather than the genes from which the cells originated. He believes that this technology will not only help doctors predict how cancer progresses, but will eventually change the way cancer is treated from a therapeutic standpoint. The technology is the keystone of the new Johns Hopkins Center for Digital Pathology, which Wirtz directs.

To understand how this technology works, consider this analogy: A cell is like a Lego brick. Just as individual Legos can come together to create a building, millions of different cells come together to make a human being. Certain bricks serve different purposes in a building in the same way that distinctive cells carry out certain functions in the body. The properties that make some Legos better suited for one purpose over another are their size and shape. For example, if a piece is flat and wide, it should go on the base. Structural characteristics that make cells unique include overall size, shape, the size and shape of the different cell parts or organelles, the composition of certain organelles, and hundreds of other parameters.

Pei-Hsun Wu of the Wirtz lab examining pancreatic cancer cells. (Photo by Mary Spiro)

Pei-Hsun Wu of the Wirtz lab examining pancreatic cancer cells. (Photo by Mary Spiro)

Wirtz’s technology uses a modified scanning electron microscope and a process called high-throughput cell phenotyping (HTCP) to instantly make hundreds of thousands of highly specific measurements defining each of these structural cellular characteristics of each single cell on a slide. Wirtz has software that uses an algorithm that adds up all of the different measurements and gives a cell a structural “score,” which quantifies the look of the cell with a number. The process will be automated and will take just minutes for a slide of cells to be analyzed and given an overall structural score, which averages the scores of all the cells on the slide.

Anirban Maitra, a professor of Oncology and Pathology at Johns Hopkins School of Medicine who is collaborating with Wirtz on this project, explains the benefits of automating this process, “If you were looking at a cell with the naked eye, you would say it has a large nucleus, medium sized nucleus, or a small nucleus. What automation allows you to do is to spread that crude three-tiered category into hundreds of small denominational events that you could then objectively add up and get a score.”

Over the course of the next five years, Wirtz plans to use HTCPanalysis as a clinically applicable tool that can help doctors treat cancer patients with more personalized therapies.

“Currently, we have a very crude approach to therapy even with the targeted therapies that are being developed. The vast majority of patients in cancer care and oncology get what are called cytotoxic agents, the old agents that were made many years ago,” said Maitra. But by using HTCP to see how cancers that look a certain way respond to certain treatments, doctors will be able to better personalize cancer treatments.

To make the project clinically applicable, Wirtz, with the help of Maitra and Ralph Hruban, also a professor of Oncology and Pathology at Johns Hopkins School of Medicine who is collaborating with the team, will be working to create the first “phenotypic database,” or a cell-feature-focused database. It will combine patient data like age, sex, cancer type, progression, treatment used, genetic sequencing results (analysis of tumor from a genetic standpoint), and so forth in an online, “cloud” database and then also add in the structure score of the patient’s tumor performed from HTCP.

At the moment, Hopkins is the only university with Wirtz’s new technology. The plan is for hospitals across the nation to begin uploading patient information to the database online and sending slides of cancer tumor cells to Hopkins or an alternate research facility using this technology. There, independent researchers will analyze the cells and add the HTCP analysis to the patient information online.

Denis Wirtz, right, working with recent PhD graduate Shyam Khatau. (Photo Will Kirk/Homewood Photography)

Denis Wirtz, right, working with recent PhD graduate Shyam Khatau. (Photo Will Kirk/Homewood Photography)

Doctors can upload all of this data into the cloud and help the database grow initially. Eventually, an oncologist in Chicago,  treating a 70-year-old man with lung cancer, and a HTCP score of X will be able to go online and find that there were two similar patients, a 65-year-old man with lung cancer in Baltimore and a 75-year-old woman with lung cancer in California, both with a score of X as well. The physician would discover that the man in Baltimore was treated with chemotherapy A and died in six months, while the woman in California was treated with chemotherapy B and was cured. Doctors will be able to make more informed treatment decisions.

Classifying the morphological characteristics of cancer is a shift from the traditional genetic approach to categorizing cancer cells. Previously, scientists researched cancer from a genetic standpoint, linking specific genetic mutations to specific cases of cancer. While this has lead to gene-targeted therapies, Wirtz wants to take a different approach to cancer research. He wants to look beyond the genetic origin of cancer and focus on what cancerous cells look like.

“We’ve come to realize that it is the heterogeneity – the diversity of cells that have different characteristics – is also important in evaluating a cancer case. In the end what matters are the cell properties.

That’s what we measure,” Wirtz explained. The rationale for this new approach, Wirtz explained, is that while cells can be identical genetically, they can vary tremendously in structure, just as two identical twins can develop to be very different people, both physically and personally. Cells from one tumor could become metastatic, latch onto a new organ, and start a new tumor that eventually kills the patient, while a genetically identical set of cells could remain localized and die as soon as they detach from the original tumor.

Wirtz’s theory is that the key to cancer treatment prognostication lies not in cancer genetics, but in the physical attributes of cancerous cells. For example, you could say that muscle definition and physical fitness would be strongly correlated with athletics and would therefore be able to be used to predict who out of twenty people would become athletes. Wirtz believes that his technology will allow doctors to do the same thing with cancer.

With this new technology Wirtz hopes to figure out what triggers cancer cells to metastasize. For example, do small, elliptical cells with large nuclei metastasize better than large, rod-like cells with small nuclei? He explained that cells that metastasize have to be super-cells, much like super-heroes are better, faster, and stronger than other humans.

“Millions of cells are shed by tumors every day, but only one or two of them will have what it takes to become metastatic. These  are the decathlon cells. We need to figure out what the physical properties are that give these cells an edge,” Wirtz says.

Maitra poses the question that guides the project in its applications towards therapeutic cancer treatment, “We have a lot of different drugs out there right now. Some work, some don’t. The problem is you only find out if they worked retroactively. You give it to a patient and six months later the metastasis keeps growing and you know if it’s worked or not. But wouldn’t it be nice if we knew going into the treatment that these patients would respond to a particular regimen and these other patients respond to another regimen?”

Maitra believes that conceptually, this project is paradigm shifting. “Wirtz is analyzing cancer in a brand new way. Extending this tool into an open-access cancer database, the project seems to have a bright future for helping doctors treat patients.”

Maitra makes sure to keep the project in perspective while being hopeful about the direction of this project, “It is very preliminary at this point. We have a long way to go before we can actually say this is a clinically applicable technology, but what we are doing right now is working our way up there.”

Center for Digital Pathology

Game Theory and Cancer

What does game theory and cancer have to do with each other. I am not sure but this interesting workshop hosted by the Princeton Physical Sciences-Oncology Center and Johns Hopkins University might help you figure that out.

An announcement about the event reads:

Screen Shot 2013-08-02 at 12.03.06 PMRegistration is now open for the Workshop on Game Theory and Cancer, scheduled on August 12-13 in Baltimore, MD, and jointly hosted by our Princeton PS-OC and Johns Hopkins University. The main goal of this workshop is to provide a dialogue between leading basic researchers and clinical investigators that would help make headway against the very stubborn problem of cancer, and to jolt the oncology community into confronting the serious clinical problems that have previously been avoided.

The flyer is pretty cool, too.  Check it out here.

Additional information and preliminary agenda can be found at: http://www.princeton.edu/psoc/training/

To register, please go to: https://prism.princeton.edu/ps-oc/regform.php

For questions about the event, email maranzam@princeton.edu or sclam@princeton.edu