2013 Johns Hopkins Nano-Bio Magazine by Institute for NanoBioTechnology

The Magazine of Johns Hopkins Institute for NanoBioTechnology | Spring 2013

Commercializing Nanotechnology

Challenges and Rewards

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INBT Alumni: Where Are They Now? Mentors Model Academic Pathway

Thank you! INBT seeks to work with industrial partners, both large established companies and start-ups, to transfer Hopkins-created technologies to market for the benefit of humanity. Corporate participation in INBT is vital to ensure that emerging technology moves from laboratory to the marketplace as well as to provide a vehicle for open exchange between Hopkins researchers and students and their counterparts in the private sector.

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Contents Johns Hopkins University Institute for NanoBioTechnology Suite 100, Croft Hall 3400 North Charles Street Baltimore, MD 21218 Phone: (410) 516-5634 Fax: (410) 516-2355 Email: inbt@jhu.edu http://inbt.jhu.edu

Featured Stories

A Digital Perspective on Cancer

International Researchers Blog

Fighting Brain Drain

Leadership Peter C. Searson Director; Joseph R. AND Lynn C. Reynolds Professor

Symposium

Denis Wirtz

2 Welcome

Associate Director;

3 Agenda

Theophilus H. Smoot Professor

Staff Ashanti Edwards Academic Program Administrator

Tom Fekete Director of Corporate Partnerships

Warren Fewster Senior Financial Analyst

Our Speakers

Research 6

Beauty is in the Eye of the Microscopist

Amoebas Get Social When Times Get Tough

Taking a Digital Perspective on Cancer

Unlocking the Mysteries of the Blood-Brain Barrier

Christie Johnson

Education

Research Service Analyst

INBT Alumni: Where Are They Now?

Sue Porterfield

International Researchers Blog About Adventures in Belgium

Administrator

Martin Rietveld Web/Animation Director

Tracy Smith Administrative Coordinator

Mary Spiro

Outreach 21

Internships Thwart Summer â&#x20AC;&#x2DC;Brain Drainâ&#x20AC;&#x2122;

Mentors Model Academic Pathway

Bringing Hopkins Solutions to the World

Science Writer;

Partnerships

Editor-in-Chief, Nano-Bio Magazine

Surmounting the Challenges of Commercializing Technology

Graphic Design Danielle Peterson Brio Design

Additional Photography Homewood Photography Johns Hopkins Pathology Photography Marty Katz

On The Cover The blood-brain barrier involves functional interactions between endothelial cells that form brain capillaries, astrocytes, and pericytes in a complex microenvironment that regulates transport between the vascular system and the brain. Illustration by Martin Rietveld

Symposium

Welcome This seventh installment of the Johns Hopkins Institute for NanoBioTechnology’s Annual Symposium may be our most unusual to date, but the topic is extremely important: commercialization of nanotechnology. Good ideas are of limited use to humanity if they do not move past the research stage. The key to technological progress is translation—bringing great ideas to the marketplace where they can actually help people. For today’s symposium, we have assembled an impressive lineup of speakers who have firsthand experience in what it means to bring an idea to market. They have suffered the challenges and setbacks, overcome obstacles and reaped the rewards (or are beginning to) of shepherding an idea from bench to bedside. Our speakers come from academia and private industry and from diverse disciplines. In addition, we have also included as our keynote presentation an extended interactive discussion with Justin Tom Fekete

Klein, a partner with the venture capital firm NEA. We expect the conversations generated today to continue for many weeks and months to come. You also hold in your hands our fourth edition of INBT’s Nano-Bio Magazine. Many of the stories in our 2013 issue expand on the theme of today’s symposium. Please share our annual magazine and symposium program with your colleagues and friends. If there is anything that we can do to make your experience at today’s symposium better, please let one of our student volunteers, who are wearing INBT shirts and name badges, or an INBT staff member know. Tom Fekete Director of Corporate Partnerships Johns Hopkins Institute for NanoBioTechnology

Johns Hopkins University Nano-Bio Magazine

Symposium

agenda 2013 Institute for NanoBioTechnology Annual Nano-Bio Symposium

Translating the Promise of Nanoscience from Laboratory to Development Friday, May 17, 2013 | 8 a.m. â&#x20AC;&#x201C; 3:30 p.m. | Shriver Auditorium

8:00 a.m. Registration

Lobby of Shriver Auditorium

Lobby of Shriver Auditorium 10:35 a.m. 8:15 a.m. Welcome

Translating Nanotechnology into Medicines:

Peter Searson, Tom Fekete 8:20 a.m.

8:45 am

Justin Hanes, Johns Hopkins University

Anthony Tuesca, MedImmune Challenges, Outlook and Perspectives

11:00 a.m.

Phil Vanek, Lonza

Nanotherapeutics: Two Basic Discoveries that

Scaling Up the Unscalable â&#x20AC;&#x201C; or Why Cellular

Launched Biopharma Start-Ups

Technologies Fail in Development

Gabriele Putz Todd, Osiris Therapeutics

11:25 a.m.

Therapeutic Potential of Mesenchymal Stem Cells

INTERACTIVE SESSION: Justin Klein, NEA Investing in Translational Science: Preparing for the Road Ahead

9:10 am

Kristin Weidemaier, BD Technologies SERS Nanotechnology for the Development of

12:30 p.m. Adjourn/Break

Medical Diagnostics

1:30 p.m.

9:35 am Jordan Green, Johns Hopkins University

Poster Session A, even numbered posters Clipper Room

Nanobiotechnology for Nucleic Acid Delivery and Artificial Antigen

2:30 p.m.

Poster Session B, odd numbered posters Clipper Room

10:00 a.m.

Peter Gabriele, Secant Medical FT-IR Microscopy: What does Surface Chemistry

3:30 p.m.

Judging Concludes and Awards

Look Like? 10:25 a.m. Break

Spring 2013

Symposium

Our Speakers

Justin Klein

Phil Vanek

Anthony Tuesca

Peter Gabriele

Justin Klein

their development of scalable commercialization strategies. He cur-

Justin Klein is a Partner on NEA’s healthcare team. He joined NEA

rently serves as the Head of Innovation for Lonza’s Bioscience Sector,

in 2006 and focuses on medical device, healthcare technology,

leading a team of 165 scientists and commercial strategists, and sits

specialty pharma and biopharmaceutical company investments.

on the Global Innovation Strategy Team for Lonza Group. Vanek

He is actively involved with NEA’s investments as a director of

earned a PhD in Biochemistry from Georgetown University Medical

Legato Medical, PhaseBio Pharmaceuticals, Relievant Medsystems,

a held an IRTA fellowship at the National Cancer Institute in the

Senseonics, Topera Medical, Ulthera, VertiFlex, and VytronUS, and

Laboratory of Molecular Oncology. He was a postdoc in the Center

as a board observer for Carticept Medical, Cartiva, ExploraMed,

for Molecular and Structural Biology at the Hollings Cancer Center

Moximed, Neuropace, and TriVascular. His past board member-

at the Medical University of South Carolina, Charleston.

ships include CV Ingenuity (acquired by Covidien in 2013). Klein is also a member of the advisory boards for the National Venture

Anthony Tuesca

Capital Association’s Medical Industry Group and its Medical

Tuesca is a scientist in the Innovative Drug Delivery Group at

Innovation and Competitiveness Coalition (MedIC). Previously,

MedImmune, where he works on the evaluation and development of

Klein worked for the Duke University Health System on strategy,

enabling and differentiating drug delivery technologies for biologics.

finance and clinical service unit operations. He has also worked at

He joined MedImmune in 2008 and has worked on over 10 clinical,

Latham & Watkins LLP in Menlo Park, where he assisted life sci-

pre-clinical and research stage programs. He earned his PhD from

ences companies on numerous licensing transactions, regulatory and

Drexel University, where he was an NSF-IGERT fellow in Nanoscale

corporate securities matters. He has served as a member of the Board

Science and Engineering. At Drexel, he studied protein conjugates

of Trustees of Duke University and previously served on the medical

and oral drug delivery technologies for the treatment of diabetes.

center’s Institutional Review Board. Klein concurrently earned his MD from the Duke University School of Medicine and his JD from

Peter Gabriele

Harvard Law School. He received his AB in Economics and his BS

Gabriele is Director of Emerging Technology at Secant Medical of

in Biological Anthropology and Anatomy from Duke University.

Perkasie, Pa. He is nationally recognized for his work in biomedical research and development, and leads Secant’s activity in building

Philip G.Vanek

strategic relationships with academia, research institutions, and sur-

Vanek is Head of Innovation at Lonza Bioscience and has worked

geon groups. Gabriele brings to Secant Medical 30 years of scientific

with many emerging-stage therapeutic companies to help support

and industrial innovation and experience in advanced biomedical

Johns Hopkins University Nano-Bio Magazine

Jordan Green

Kristin Weidemaier

Gabriele Putz Todd

Justin Hanes

technologies, including polymers, photo-imaging, fiber optics,

She has a PhD in physical chemistry from Stanford University and

and bone adhesives. He holds two master’s degrees, one from

an undergraduate degree from Duke University.

Johns Hopkins University in Biotechnology and another in Technology Management the University of Pennsylvania Wharton School

Gabriele Putz Todd

of Business.

Todd is a Senior Scientist at Osiris Therapeutics, Discovery and Development in Columbia, Md. She has wide range of technical

Jordan Green

skills and scientific background including stem cell research, cancer

Green’s Biomaterials and Drug Delivery Laboratory is acutely inter-

research, neurobiology, human genetics, and ecology. Todd has

ested in biomaterials, drug delivery, gene therapy, nanobiotechnol-

been a dedicated project and laboratory manager with more than

ogy, and cell engineering. Research findings — and the technologies

15 years of experience conducting complex research projects within

developed — are applied in the fields of ophthalmology, oncology,

the biological and medical field. She earned a PhD in Genetics and

and regenerative medicine. His lab works within the chemistry/

Neurobiology from the Julius-Maximilians-Universität Würzburg

biology/engineering interface to answer fundamental scientific

(Germany) and held a postdoctoral position at the Max Planck

questions, and to create innovative technologies and therapeutics

Institute of Molecular Cell Biology and Genetics.

that can directly benefit human health. Green earned his PhD in Biological Engineering at MIT and his bachelor’s degree in Chemi-

Justin Hanes

cal Engineering, Biomedical Engineering from Carnegie Mellon

Hanes is the Lewis J. Ort Family Professor and Director of the

University.

Center for Nanomedicine at the Johns Hopkins University School of Medicine with a primary appointment in Ophthalmology. He is

Kristin Weidemaier

a founder and is on the board of directors of Kala Pharmaceuticals,

Weidemaier is a Senior Manager in Becton Dickinson’s Biosensors

a company commercializing mucus penetrating particle nanotech-

department, where she has spent the past 10 years designing biosen-

nology. Hanes also founded and is CEO and Chair of the Board of

sors and in vitro diagnostics. Her group works on new technol-

Directors of GrayBug, a private company developing advanced drug

ogy development, with an emphasis on taking technology from

delivery systems with a special focus on the treatment of diseases

a feasibility stage through to product development. She currently

that affect vision. He received a PhD in Chemical Engineering from

leads BD’s nanotechnology R&D program, which is focused on

MIT and did postdoctoral training in Oncology and Neurosurgery

nanotechnology-based diagnostics for Point-of-Care applications.

at the Johns Hopkins University School of Medicine.

Spring 2013

Research

Perinuclear actin cap stress fibers in a mouse embryonic fibroblast.

Johns Hopkins University Nano-Bio Magazine

Photo by Dong-Hwee Kim

Beauty is in the Eye of the Microscopist By Mary Spiro

Scientists have been using microscopes to produce up-close views

the Biophysical Society’s, The Art of Science Image Contest for his

and gather data about cells and other tiny things for more than

dandelion-like representation of the geodesic actin network in a

400 years. Many times, however, those images are not just informa-

mouse fibroblast.

tive, they are beautiful. Dong-Hwee Kim, a postdoctoral fellow in the Institute for

Kim says his primary focus in collecting these images has always been purely for scientific purposes. “I am trying to better under-

NanoBioTechnology in the Whiting School of Engineering,

stand how cells recognize the physical properties of the cell envi-

frequently uses microscopy in his research on cell mechanics, a field

ronment and respond to them,” he said.

he describes as “one of the fastest growing interdisciplinary fields in biology.” Several of his images have not only yielded abundant quantita-

Engineers have developed theories about cell mechanics and about what they expect to happen at the single cell level. But instead of describing the cell’s response with a computational model

tive and qualitative data, but they have netted him awards for

or other simulation, Kim was determined to capture actual images

scientific imaging. In 2011 he earned an Image of Distinction

of live cells reacting to their surroundings.

Award from the Nikon Small World Competition for his photo

“Direct visualization of cell functions has become one of the most

of a disorganized perinuclear actin cap stress fibers in a mouse

effective ways to support scientific findings, since it is the simplest

embryonic fibroblast. That same year, he was awarded an Honor-

but most powerful way to convince others,” he said. Using various

able mention from the American Society for Cell Biology 7th

microscopy techniques, Kim has been able to visualize cell compo-

Annual Cell Biology film contest for his movie “Hurricane: Cell

nents, such as the nucleus or actin filaments, in very detailed ways.

Cytoplasm Movements”. And in 2013, Kim took second place in

“It is always exciting to become the first one to show something that others haven't seen yet,” he said.

Spring 2013

Research

Denis Wirtz, Kim’s advisor, noticed how beautiful the postdoc’s images were turning out and suggested that he enter some of his

gives them unparalleled power to support scientific findings and persuade others,” Kim said.

work into popular imaging contests. Each contest focuses on a

The old saying goes, “a picture is worth 1,000 words.” In this

different theme, but the bottom line is that the images must be

case an expertly executed scientific image “can overcome myriad

scientifically relevant as well as visually interesting. For example,

arguments,” Kim added.

the image of the geodesic actin network in the mouse embryonic

Kim said his favorite imaging tool is the “confocal laser scanning

fibroblasts, which were used for both the Nikon and Biophysical

microscopy, which allows high resolution images in cell biology, as

Society image contests, “directly visualized the mechanical and spa-

well as qualitative and quantitative analysis of images.” He empha-

tial coordinates of filamentous actin cytoskeleton in the cell,” said

sizes that he does not use any software enhancements, such as Pho-

Kim. But the images also happen to be reminiscent of dandelions

toshop, to beautify his images. However, by attempting to create a

and fireworks.

beautiful image, he has developed several new imaging protocols.

Even if making a pretty picture is not the intent of the image, Kim thinks that having an artistic eye is important in science. “I think artistic images in science should be based on a combination of aesthetic discrimination and scientific significance, which

“In challenging myself to create artistic images, it has sometimes led me to design new scientific methodologies that were not conventionally used in the field, and I think these efforts can contribute to the advancement of science,” Kim said.

Actin network in a mouse fibroblast.

Johns Hopkins University Nano-Bio Magazine

Photo by Dong-Hwee Kim

Amoebas Get Social When Times Get Tough By Rezina Siddique

How single-celled social amoebae respond to chemical signals is

mechanism of signal amplification that occurred in the amoeba,

shedding light on the processes and behavior of more complex

but there was no way to test it. However, using their microfluidic

organisms, including mammals. A recent paper suggests that there

pattern generator, Levchenko’s group was able to validate the

is a mechanism by which amoeba amplify a desirable chemical

model experimentally. “Understanding the dynamics of chemotaxis

stimulus in order to self-organize and collectively migrate.

within this system can shed insight into how other multicellular

Amoeba are single-celled organisms with the capability to ag-

organisms, as well as how mammalian cells interact,” Levchenko said.

gregate to form a multi-cellular organism, and later to a fruiting

During aggregation, cyclic AMP (cAMP), a molecule that

body. Andre Levchenko, professor of biomedical engineering and

stimulates hunger, serves as chemoattractant. A starving social

affiliated faculty member of Johns Hopkins Institute for NanoBio-

amoeba secretes cAMP to attract other amoebae to it, which all

Technology, used the social amoeba, Dictyostelium discoideum,

travel towards the central amoeba. These other cells also start

because as a multicellular organism it contains cells with different

releasing cAMP in a periodic fashion in order to amplify the signal

genotypes. Levchenko’s team sought to clarify how external signals

and attract additional amoebae, creating a pulsating and wave-like

were amplified by the organism to facilitate aggregation.

signal. An individual cell ends up seeing waves of activity. This

“The way [these organisms] detect signals and move are similar to how neutrophils, a natural part of our immune system, detect

is similar to pacemaker cells in the heart, where periodic activity regulates cell behavior.

and move to the site of infection…They share the ability to migrate

In a population of cells, some cells are more sensitive while oth-

in a very directed way to get where they are needed,” said Levchen-

ers are less sensitive. This discrepancy is not visible when averaging

ko. When resources are plentiful, Levchenko’s team found that

the response over the entire population or when examining a single

Dicty are content in remain alone. But when food supplies run

representative cell. By applying the hunger stimulus to cells within

low, they gather into a multicellular slug.

their device, Levchenko’s group found that there is a large differ-

As a slug, he said, “they can move together to find a more favor-

ence across cells in a given population. Some cells did not respond

able location,” said Levchenko. The cell-cell communication that

at all, while others responded very strongly to the same stimulus.

takes place during the transition relies on chemotaxis, which is the

They also found that at higher doses, the majority of cells re-

movement towards or away from a chemical stimulus along a con-

sponded, while at lower doses, smaller numbers of cells responded.

centration gradient. This behavior is similar in mammalian cells,

This indicates that the cells that respond strongly must have some

relevant in both healthy and pathological conditions. Their results,

ability to amplify the signal.

are published in volume 5, issue 213 of Science Signaling.

Differential sensitivity in the cells helps them to organize. Ad-

Levchenko’s team developed a microfluidic pattern generating

aptation allows them to transiently suppress their sensitivity long

device that allows the user to control the environment and stimulus

enough to be able to form a multi-cellular organism. The adaptive

duration in a highly tunable way, while still being able to visualize

and amplification properties of the amoeba resemble what occurs

cells under a microscope. Historically, Levchenko explained, these

in bacterial chemotaxis. The results have implications for the study

types of experiments were done with pipettes, but with the device

of cell decision making versus commitment to behavior within cells

his group was able to perform their experiments with the dynamic

of a given tissue, or different types of cells that work together.

signaling responses consistent with the known behavior of the amoeba. Previously, a mathematical model was developed to explain the

Rezina Siddique is a Ph.D. student in Biomedical Engineering at Johns Hopkins with an M.S. in Nanoscale Science and Engineering.

Spring 2013

Research

Pei-Hsun Wu of the Wirtz Lab examining pancreatic cancer cells.

Taking a Digital Perspective on Cancer By Bryan Kohrs

10 Johns Hopkins University Nano-Bio Magazine

Photo by Mary Spiro

Denis Wirtz lines up next to many other scientists in the war on

Over the course of the next five years, Wirtz plans to use HTCP

cancer. But while others battle with familiar technologies and ideas,

analysis as a clinically applicable tool that can help doctors treat

Wirtz has armed himself with a new imaging technology, a fresh

cancer patients with more personalized therapies.

strategy on how to better combat this dreaded disease and a fiveyear grant from the National Cancer Institute (NCI). Wirtz, a professor of Chemical and Biomolecular Engineering at

“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 cyto-

Johns Hopkins, is carving out a niche for himself in cancer research

toxic agents, the old agents that were made many years ago,” said

by focusing on the look and physical structure of cancerous cells

Maitra. But by using HTCP to see how cancers that look a certain

rather than the genes from which the cells originated. He believes

way respond to certain treatments, doctors will be able to better

that this technology will not only help doctors predict how cancer

personalize cancer treatments.

progresses, but will eventually change the way cancer is treated

To make the project clinically applicable, Wirtz, with the help

from a therapeutic standpoint. The technology is the keystone of

of Maitra and Ralph Hruban, also a professor of Oncology and Pa-

the new Johns Hopkins Center for Digital Pathology, which Wirtz

thology at Johns Hopkins School of Medicine who is collaborating

will direct.

with the team, will be working to create the first “phenotypic da-

To understand how this technology works, consider this analogy:

tabase,” or a cell-feature-focused database. It will combine patient

A cell is like a Lego brick. Just as individual Legos can come

data like age, sex, cancer type, progression, treatment used, genetic

together to create a building, millions of different cells come

sequencing results (analysis of tumor from a genetic standpoint),

together to make a human being. Certain bricks serve different

and so forth in an online, “cloud” database and then also add in

purposes in a building in the same way that distinctive cells carry

the structure score of the patient’s tumor performed from HTCP.

out certain functions in the body. The properties that make some

At the moment, Hopkins is the only university with Wirtz’s new

Legos better suited for one purpose over another are their size and

technology. The plan is for hospitals across the nation to begin

shape. For example, if a piece is flat and wide, it should go on

uploading patient information to the database online and sending

the base. Structural characteristics that make cells unique include

slides of cancer tumor cells to Hopkins or an alternate research

overall size, shape, the size and shape of the different cell parts or

facility using this technology. There, independent researchers will

organelles, the composition of certain organelles, and hundreds of

analyze the cells and add the HTCP analysis to the patient infor-

other parameters.

mation online.

Wirtz’s technology uses a modified scanning electron microscope

Doctors can upload all of this data into the cloud and help

and a process called high-throughput cell phenotyping (HTCP) to

the database grow initially. Eventually, an oncologist in Chicago,

instantly make hundreds of thousands of highly specific measure-

treating a 70-year-old man with lung cancer, and a HTCP score

ments defining each of these structural cellular characteristics

of X will be able to go online and find that there were two similar

of each single cell on a slide. Wirtz has software that uses an

patients, a 65-year-old man with lung cancer in Baltimore and

algorithm that adds up all of the different measurements and gives

a 75-year-old woman with lung cancer in California, both with

a cell a structural “score,” which quantifies the look of the cell with

a score of X as well. The physician would discover that the man

a number. The process will be automated and will take just minutes

in Baltimore was treated with chemotherapy A and died in six

for a slide of cells to be analyzed and given an overall structural

months, while the woman in California was treated with che-

score, which averages the scores of all the cells on the slide.

motherapy B and was cured. Doctors will be able to make more

Anirban Maitra, a professor of Oncology and Pathology at Johns Hopkins School of Medicine who is collaborating with Wirtz on

informed treatment decisions. Classifying the morphological characteristics of cancer is a shift

this project, explains the benefits of automating this process, “If

from the traditional genetic approach to categorizing cancer cells.

you were looking at a cell with the naked eye, you would say it has

Previously, scientists researched cancer from a genetic standpoint,

a large nucleus, medium sized nucleus, or a small nucleus. What

linking specific genetic mutations to specific cases of cancer. While

automation allows you to do is to spread that crude three-tiered

this has lead to gene-targeted therapies, Wirtz wants to take a dif-

category into hundreds of small denominational events that you

ferent approach to cancer research. He wants to look beyond the

could then objectively add up and get a score.”

genetic origin of cancer and focus on what cancerous cells look like.

Spring 2013 11

Research

Pancreatic tissue.

“We’ve come to realize that it is the heterogeneity – the diversity

“Millions of cells are shed by tumors every day, but only one or

of cells that have different characteristics – is also important in

two of them will have what it takes to become metastatic. These

evaluating a cancer case. In the end what matters are the cell prop-

are the decathlon cells. We need to figure out what the physical

erties. That’s what we measure,” Wirtz explained.

properties are that give these cells an edge,” Wirtz says.

The rationale for this new approach, Wirtz explained, is that

Maitra poses the question that guides the project in its appli-

while cells can be identical genetically, they can vary tremendously

cations towards therapeutic cancer treatment, “We have a lot of

in structure, just as two identical twins can develop to be very dif-

different drugs out there right now. Some work, some don’t. The

ferent people, both physically and personally. Cells from one tumor

problem is you only find out if they worked retroactively. You give

could become metastatic, latch onto a new organ, and start a new

it to a patient and six months later the metastasis keeps growing

tumor that eventually kills the patient, while a genetically identical

and you know if it’s worked or not. But wouldn’t it be nice if we

set of cells could remain localized and die as soon as they detach

knew going into the treatment that these patients would respond

from the original tumor.

to a particular regimen and these other patients respond to another

Wirtz’s theory is that the key to cancer treatment prognostication lies not in cancer genetics, but in the physical attributes of

regimen?” Maitra believes that conceptually, this project is paradigm shift-

cancerous cells. For example, you could say that muscle definition

ing. “Wirtz is analyzing cancer in a brand new way. Extending this

and physical fitness would be strongly correlated with athletics and

tool into an open-access cancer database, the project seems to have

would therefore be able to be used to predict who out of twenty

a bright future for helping doctors treat patients.”

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 trig-

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

gers cancer cells to metastasize. For example, do small, elliptical

this is a clinically applicable technology, but what we are doing

cells with large nuclei metastasize better than large, rod-like cells

right now is working our way up there.”

with small nuclei? He explained that cells that metastasize have to be super-cells, much like super-heroes are better, faster, and stron-

Bryan Kohrs is a junior in Biophysics at Johns Hopkins University

ger than other humans.

with a strong interest in science writing and science.

12 Johns Hopkins University Nano-Bio Magazine

Image by JHMI Pathology

The blood-brain barrier involves functional interactions between endothelial cells that form brain capillaries, astrocytes, and pericytes in a complex microenvironment.

Unlocking the Mysteries of the Blood-Brain Barrier By Mary Spiro

It might astonish you to know that, although we use our brains all

of helping to prevent and even cure neurological diseases, such

the time, science knows very little about how they actually work.

as Alzheimer’s or Parkinson’s, that affect as many as 100 million

That is why recently, President Barack Obama announced a $100

Americans.

million initiative to map the human brain. “We can identify galaxies light-years away; we can study particles

Johns Hopkins University is at the forefront of brain science research. The Brain Science Institute (BSi) at the Johns Hopkins

smaller than an atom; but we still haven’t unlocked the mysteries of

School of Medicine was launched to develop new multidisciplinary

the three pounds of matter that sits between our ears,” Obama said

research teams; create cutting edge-research cores for use by all

in a press conference on the announcement April 2.

brain researchers at Hopkins; and foster translation of discoveries

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 goal

Illustration by Martin Rietveld

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 engi-

Spring 2013 13

Research

neering and director of Johns Hopkins Institute for NanoBioTech-

nately, animal models are insufficient for use in understanding how

nology (INBT), joined forces with Jeffrey Rothstein MD, PhD,

the human blood-brain barrier functions or responds to drugs. In

director of the BSi, to create the Blood-Brain Barrier Working

addition, little is known about how disease, inflammation or stroke

Group. This group brings together researchers with diverse interests

disrupts or damages the blood-brain barrier.”

and expertise to address key problems associated with drug deliv-

With this in mind, the BBB working group has two primary

ery, to discover the role of the blood-brain barrier (BBB) in disease,

goals, Searson explained. “Our long-term goal is to build an arti-

and to elucidate the structure and function of the BBB.

ficial microvessel that will be the first platform that recapitulates

“The blood-brain barrier is a dynamic interface that separates the

a brain capillary in its local microenvironment. This will enable

brain from the circulatory system and protects the central nervous

fundamental studies as well as drug discovery and the development

system from potentially harmful chemicals while, at the same time,

of methods to cross the blood-brain barrier,” Searson said.

regulating transport of essential molecules and maintaining a stable

The second goal is to understand how the blood-brain barrier

environment,” Searson said. “It is formed from highly specialized

can be damaged or disrupted so that strategies can be developed to

endothelial cells that line the brain capillaries, which transduce

repair it. Injury and disease can disrupt the normal structure and

signals in two directions: from the vascular system and from the

function of the blood brain barrier.

brain. The structure and function of the BBB is dependent upon

Currently the BBB Working Group has 40 researchers from

the complex interplay between different cell types, specifically the

disciplines as diverse as anesthesiology, materials science and engi-

endothelial cells, astrocytes and pericytes, within the extracellular

neering, pharmacology and oncology. Three postdoctoral fellows

matrix of the brain and with the blood flow in the capillaries.”

and 12 pre-doctoral students are also involved. The group meets

Although the BBB serves the important purpose of tightly

monthly and hosts expert speakers on various topics. The working

regulating the environment of the brain and preventing sud-

group website also lists current funding opportunities to which

den changes, which the brain cannot tolerate, Searson said, “this

members can apply and conferences and workshops of interest.

interface also blocks the passage of drug molecules to treat disease,

Membership in the working group is open to any student, faculty

neurodegenerative disorders, inflammation or stroke. Unfortu-

member or staff at Johns Hopkins University in any discipline.

14 Johns Hopkins University Nano-Bio Magazine

Illustration by Martin Rietveld

Education

INBT Alumni: Where Are They Now? By Mary Spiro

A mission of Johns Hopkins Institute for

to learn skills outside of their primary

NanoBioTechnology since its founding in 2006 has been to edu-

degree area. They take specially de-

cate the next generation of scientists and engineers to work at the

signed courses such as Nano-Bio Labo-

interface of nanotechnology and medicine. Over the last seven years, INBT has partially funded the graduate educations of seven cohorts of doctoral students (more than 50 students so far) through a variety of nano-bio training programs. These programs have included a National Science Foundation IGERT (Integrative Graduate Education

ratory and Communication for Scientists and Engineers. And each cohort also meets for a weekly journal club, which gives them the opportunity for peer-to-peer training. How do all these added requirements and expanded experiences impact INBT graduates in their

and Research Traineeship), a Howard Hughes Medi-

professional careers. Some of the first INBT trainees are

cal Institution training program, the Cancer Nano-

making their way into the professional realm, so we wanted

technology Training Center and, in the case of one

to find out. To get to the heart of their experience, we asked

student, a partnership with Northrop Grumman.

the graduates several basic questions: What is your current

Usually after four to six years of hard work and the support of their advisors, these students complete

job? What was one of the most important lessons or experiences you had while working as an INBT doctoral trainee?

all their research and educational requirements

What nonacademic benefits did you derive as an INBT

and earn their PhDs. In the case of INBT, stu-

trainee? Some definite themes emerged. Here is what a

dents have two advisors from different depart-

few of them had to say about the benefits of an â&#x20AC;&#x153;INBT-

ments. They rotate working in the laboratories

brandedâ&#x20AC;? Johns Hopkins University doctoral degree.

of each of their advisors to offer them the chance

Spring 2013 15

Education

Maureen Wanjare, left, with Lauara Dickinson in the Gerecht Lab.

Laura Dickinson, (PhD, Chemical and Biomolecular Engineering) is postdoctoral researcher in the lab of Dr. Nynke Dekker at the Delft University of Technology in the Netherlands. “What I found rewarding was that I was able to do things in the

that is the case for most PhD students, but that is wrong. In the

Nano-Bio Lab, such as making quantum dots, that I wouldn’t

INBT cohort I was a part of, we were a hodgepodge of students

normally have been able to do. The extra requirements, although

from different research areas and departments (computer science,

interesting and very valuable in hindsight, added extra anxiety

chemistry, engineering). Through our weekly meetings, we taught

and stress. What I found most interesting was interacting with

and shared with each other important findings or fundamentals

PhD students that I might not have had the chance to otherwise

from our own fields of research. In the end, it made me realize that

because they were in different departments. When I started my

all our disciplines are interconnected in some way, and that we

PhD, I assumed that during my time at Hopkins I would always

were all just using different methods/technologies to solve the same

be within my small scientific niche, only interacting with those

societal/health problems. I also really enjoyed the chance to live

in my research group, or in very similar fields as my own, because

and work abroad for three months at IMEC in Belgium”.

that would be most beneficial to my specialization. And I believe

16 Johns Hopkins University Nano-Bio Magazine

Photo by Marty Katz

Jacob Koskimaki (PhD, Biomedical Engineering) is a postdoc-

was a really wonderful experience that I had with INBT. Not only

toral research fellow in the Department of Biomedical Engi-

was it academically challenging but interesting. And the personal

neering at the University of Virginia.

interaction with the INBT staff members was great. They are doing

“The INBT training program gave me exposure to course work,

an awesome job!

collaborations and other students outside of my immediate discipline of biomedical engineering. This proved to be a huge asset in planning my dissertation work. In addition, I had expertise in biomedical engineering and bioinformatics that was immediately useful to my collaborators. INBT taught me to read and learn broadly across scientific disciplines, and more importantly to see that as an asset for my professional development as a scientist and engineer. Often the most creative insights and discoveries occur through collaborations at the interface of different disciplines. I have kept in contact with several of my INBT friends and collaborators. We have referred one another to various job postings and prospects that have also widened the possible career choices I will consider after my postdoctoral fellowship. We also received training in effective science writing and communication, even with video. I found in graduate school many students received no formal training in such matters. Without an effective way to communicate the big picture of complex, difficult science, the greater impact is sometimes lost. I hope collaborative, interdisciplinary institutions such as INBT continue to thrive. I found it to be an instrumental part of my growth and development of professional skills at Hopkins.” Stephen Diegelmann

Tommy Tong (PhD, Chemical and Biomolecular Engineering) is a postdoctoral researcher at the Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain. “I had the opportunity to take challenging courses in addition to the ones that are required from our own department. We got to learn subjects ranging from cell biology to material science. It was rewarding to learn from professors who are the experts in their fields. The most important experience that I had was the interaction with my cohort. We met on a regular basis to discuss science and also our personal lives. We basically grew together during those years. In journal club, we would teach each other about our re-

Stephen Diegelmann (PhD, Chemistry) is a postdoc in the polymer engineering department at Case Western Reserve University. Since his contract is nearly complete, he’s actively interviewing for industrial polymer chemist jobs.

search fields and also help each other in many other ways. Through

“I think the best thing I was able to take away from the INBT

INBT, I had professional development training. We were exposed

training program was the interaction with so many other scientific

to useful workshops such as grant writing, job searching skills etc.

backgrounds. We all had very different interests, skill sets, training,

Speakers were invited to share their achievements with us. More-

and even scientific vocabularies, but throughout the four to five

over, there are many gatherings that INBT hosted that also invited

years of classes, labs, and journal club, we all were able to commu-

people from industry, which gave us a perspective that was differ-

nicate and appreciate and learn about everyone’s background. I also

ent from the academic setting. They were not only sharing their

made some good friends and had the opportunity to mentor two

experiences, but also serving as contacts for future job searches. It

summer research interns through the INBT program.”

Photo by Marty Katz

Spring 2013 17

Education

Shyam B. Khatau, (PhD, Chemical and Biomolecular Engineering) is a postdoctoral researcher at the Johns Hopkins Physical Sciences-Oncology Center and an intern in Business Development and Strategic Alliances at the Johns Hopkins Medical Institutions. “INBT gave me the opportunity to learn with and from scientists and engineers from all disciplines. Even when the material was over my head, or I didn’t pay attention in class, I was gaining an understanding of science beyond my own. Also, the focus on the bigger

picture was important for (a) shaping my scientific views and (b) staying motivated during grad school. The most important lesson I learned was the value of interdisciplinary teamwork. In terms of non-academic benefits, I have been able to network with peers and industry people. Plus INBT is a cool experience to talk about in interviews. Frankly, I think it should be the only way to learn.” Justin Galloway (PhD, Materials Science and Engineering) has started working for a recently launched start up company called Twistnostics, which was founded by another former INBT affiliate Alfredo Celedon. They are looking to manipulate the unique properties of DNA for biodetection and possible pointof-care diagnostics. “The program gave me lofty ideas about what could and should be accomplished in graduate school. With so many excellent faculty members, postdocs and other graduate students available to collaborate with and seek advice from it made setting lofty goals seem

Shyam Khatau with his advisor Denis Wirtz.

18 Johns Hopkins University Nano-Bio Magazine

attainable. I think it also made these discussions more exciting because ideas from different perspectives often generated unique solutions. Science performed by scientists is often narrow in scope and focus. Different fields often speak totally different languages and the opportunity for collaboration is often lost in the disconnect. Doing graduate work in both a biology lab and material science really made me appreciate how important it is just learning to communicate. I think the people I met were the best benefit of INBT. Interacting with people from the medical school and other engineering and natural science disciplines was a unique experience that I think more graduate students should have. INBT participated in the USA Science and Engineering Festival in 2010 on the National Mall. We interacted with a lot of kids, and it was exciting to see how excited these kids were doing simple science experi-

Janice Lin

ments. Likewise, I think INBT let me be a little kid for a few years and do fun and exciting cutting edge science.

Janice Lin (PhD, Materials Science and Engineering) works as a senior engineer for Becton Dickinson. She is currently at BD Biosciences in San Jose, Calif., but spent the last two years at BD Medical in Sandy, Utah. “I didn’t feel that the program made anything challenging, rather it gave me the opportunity to see what other students in other departments were doing. I really liked learning about that because it opened up doors for potential collaborations, but also just simply provided me more exposure to the different types of research being conducted. Just having two professors’ inputs and opinions on how research should be conducted and writing papers alongside them was invaluable. Everybody has a different take on it, but working with two professors with excellent publications records and seeing how they approach research (however differently) was something I greatly appreciated. As for nonacademic benefits: extra money for supplies? Sorry, but seeing the wealth of free Apple laptops surely made other grad students envious. There really wasn’t that much more work associated with being in INBT, certainly for me nothing to complain about. I thought the extra courses were interesting and sometimes really fun (the video course!).

sends Read more INBT alumni profiles online at http://inbt.jhu.edu/education/alumni/

Photos by Marty Katz

Spring 2013 19

Education

International Researchers Blog About Adventures in Belgium By Mary Spiro

Each summer, Johns Hopkins Institute for NanoBioTechnology

devices. Internships can last a few weeks to a couple of months

supports research internships abroad and what better way for those

depending on the project. Participants spend plenty of time in the

touring scientists and engineers to keep in touch with colleagues

lab, but they also have many opportunities to explore Belgium

back home than with a blog.

and the neighboring countries, such as England and France. Their

INBT’s International Research Experience for Students (IRES) program, funded by the National Science Foundation, sends students to work with researchers at The Inter-University Mircro-

adventures are featured on the blog INBT’s Summer at IMEC Research Program, http://inbt-summer-at-imec.blogspot.com/ During the summer of 2012, five students from Johns Hopkins

Electronics Centre (IMEC) in Leuven, Belgium. Students conduct

conducted research at IMEC. Gregg Duncan, a doctoral student

experiments at IMEC’s world-class microfabrication facility and

in the lab of Michael Bevan, associate professor of chemical and

learn to design, fabricate and test a wide range of biomedical

biomolecular engineering, used dark field microscopy to quantify nanoparticle-cell interactions. Colin Paul, doctoral student in the lab of Konstantinos Konstantopoulos, professor and chair of the Department of Chemical and Biomolecular Engineering, brought cell migration devices fabricated in the Konstantopoulos lab to IMEC to perform proof-of-concept experiments with Nicolas Barbera, a rising senior working in the same lab. Barbera gained skills in fluorescence microscopy, dark field microscopy and hyperspectral imaging. Sarah Friedrich, a doctoral student from the laboratory of Andre Levchenko, professor of biomedical engineering, worked on a plat-form that could expose cells to both chemical and topographical stimulation at the same time. And Peter Nelson, a rising sophomore working in the lab of Jordan Green, assistant professor of biomedical engineering, was developing a polymer-nanoparticle with the ability to apply hyperthermia (heat) and chemotherapy treatments. They also hit the beach, toured museums, sampled international cuisine, road bikes and bought waffles from vending machines. You know you are in Belgium when waffles are served fast food style. Now what did you do on your summer vacation?

20 Johns Hopkins University Nano-Bio Magazine

Outreach

Christopher Miller, left, with his mentor Hoku West-Foyle.

Internships Thwart Summer “Brain Drain” By Mary Spiro

For most teenagers, finding a summer job is almost a rite of pas-

The Summer Academic Research Experience (SARE) program,

sage into adulthood. It’s a chance to learn responsibility and time

an opportunity funded in part by Johns Hopkins Institute for

management and practice how to get along with coworkers. It also

NanoBioTechnology and the School of Medicine, trains students

helps earn money for college or fun. A group of specially selected

from “disadvantaged” homes throughout the state. Some students

teens, however, were able to take the concept of the summer job a

may have a parent in prison or struggling with addiction. Others

step further as summer research scholars in Johns Hopkins Univer-

may face extreme financial hardship or even have been homeless.

sity laboratories.

Photo by Mary Spiro

Spring 2013 21

Outreach

SARE scholars have a chance to overcome obstacles to academic

learning curve is steep. But with mentoring from graduate students

success by working in academia under the guidance of a mentor.

and postdoctoral fellows, the scholars find their way. At the end of

They improve their writing and mathematics skills through tutor-

the summer, the scholars present their findings in a poster session

ing. And they learn how to keep good laboratory records, how to

for their peers, faculty and staff.

follow safety protocols, and how to make a professional presentation.

“At the beginning of the summer, I didn’t know what the heck

“This is way better than flipping burgers,” exclaimed Stephanie

I was talking about, but now I get it!” laughed Christopher Miller,

Keyaka, as she prepared an image of a Western Blot performed on

a tenth grader from The SEED School. Miller studied the motor

Drosophila eye genes. Keyaka is a tenth grader from The SEED

protein myosin in the Robinson lab.

School of Maryland, the state’s only public boarding school. She

Miller’s mentor, cell biology doctoral student Hoku West-Foyle,

studied rhodopsin in the eyes of flies in the lab of professor Craig

said working with students during the summer helps to re-energize

Montell during the summer of 2012.

the lab. “At first, it is a bit of extra work, but it gives you teaching

SARE, launched in 2009 through a collaboration between

experience, and when you are explaining your project to other

INBT and School of Medicine cell biology associate professor

people, it helps to reinforce why the larger research question matters.

Doug Robinson, recruits students from the private nonprofit Boys

It fires you up to work harder,” West-Foyle said.

Hope Girls Hope of Baltimore, from The SEED School, and now

Shaolin Holloman, an eleventh grader at Baltimore Polytechnic

also from The Crossroads School, operated by the nonprofit Living

Institute and Girls Hope scholar, worked in the cell biology lab of

Classrooms Foundation. While the partnership with Boys Hope

professor Carolyn Machamer. Her project sought to understand why

Girls Hope has been in place from the beginning, working with

the SARS coronavirus localizes to the Golgi apparatus of the cell.

The SEED School and The Crossroads School has expanded the

“I liked the work experience because we actually got to do hands-

potential pool of qualified and interested applicants. “Expanding

on experiments,” said Hollomon, who hopes to become an ortho-

the applicant pool makes the program more competitive, which

pedic surgeon. “The biggest challenge for me was to keep up with

is a worthwhile experience—to have to compete for something,”

my weekly essays, my summer reading and the work in the lab.”

Robinson said.

Robinson hopes the program can become self-sustaining and

During their time at Hopkins, each SARE scholar focuses on a

even scalable to accept more students. “We are at a juncture where

mini research project that advances the larger goals of the lab where

we are seeking additional funding, so we are systematically assess-

they are placed. No prior laboratory work is expected, and the

ing our impact,” Robinson said. One would judge that the SARE program’s impact is significant, since all five alumni who have graduated from high school, or who will do so this spring, have

Shaolin Holloman with Carolyn Machamer.

gone on to university, Robinson reported. Two students have declared biology as their major and the other three still in high school are interested in science, technology, mathematics or health-related disciplines. Five new scholars will join SARE this summer. Khalek Kirkland, The SEED School headmaster said summer internships of this kind are important to help keep students motivated and on track academically. “We do believe in the ‘summer brain drain,’ in that students do lose something over the summer,” Kirkland explained. “Doug and I are in talks about writing a grant together to expand the program not only to SEED School students, but to additional students as well.” Anyone with interest in supporting the efforts of the SARE program can contact Robinson via email a drobin15@jhmi.edu.

22 Johns Hopkins University Nano-Bio Magazine

Charli Dawidczyk helping students attach magnets to their foam plate speakers.

Mentors Model Academic Pathway By Colin Paul

When I was in high school, I had an inspiring chemistry teacher.

magazine of the School of Advanced International Studies, Hop-

He was funny, he rewarded hard work, and he let us light salt fires

kins president Ron Daniels stated the need for Hopkins to help

in paths around the soapstone lab benches in his classroom. He

revitalize Baltimore and outlined some of the initiatives to do so.

stayed after school to help my twin brother and me build a “ChemE

Faculty, staff, and trainees at Johns Hopkins Institute for Nano-

Car” that used a chemical reaction to stop after a given distance,

BioTechnology (INBT) are challenged to become more involved

and we placed second in a competition for local high schools held

in mentoring pre-college students. Recently, INBT partnered with

by the University of Tulsa. He made the subject interesting, and his

the Incentive Mentoring Program (IMP) to hold a “Science Day”

passion for it was contagious.

for students at the Academy for College and Career Exploration

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

(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

science. Mentorship is particularly important to underrepresented

graduating. The program has grown to incorporate several hundred

groups in the sciences, such as minorities or women. It’s so important

volunteers from the East Baltimore and Homewood Hopkins cam-

that the National Institutes of Health supports science education and

puses. IMP provides comprehensive mentoring and tutoring

outreach through its Office of Science Education, and the National

to enrolled students, offering educational, legal, and career support

Science Foundation has made it a goal “to expand efforts to increase

to the students and their families. IMP is not merely a tutor-

participation from underrepresented groups and diverse institutions

ing program in which volunteers help students with homework.

throughout the United States in all NSF activities and programs.”

Instead, it provides students with the social support they may

Johns Hopkins University is also increasingly leading efforts to improve Baltimore communities. In an editorial published in the

Photo by Mary Spiro

otherwise lack. Teams of five to six mentors are assigned to each student, and these mentors coalesce into an extended family

Spring 2013 23

Outreach

around the student, many of whom come from environments

liquid ice cream mix. The students made excellent chefs and were

where even graduating from high school is an obstacle. So far,

excited to see water vapor roil over the lip of the bowl as liquid

all of the students enrolled in IMP have earned their high school

nitrogen was stirred in to freeze the cream. The recipe got several

diplomas or equivalent degree.

thumbs up, and the demonstration really held their attention.

As IMP grew, students from the laboratories of INBT-affiliated

I hope the students saw how science comes up in everyday life,

faculty members Peter Searson, Konstantinos Konstantopoulos,

even in things we don’t always think about, like music and cooking.

Hai-Quan Mao, Justin Hanes, and Andre Levchenko started

By having fun and doing experiments with their mentors and

to get involved. INBT sought to unite the groups for an event to

friends, they may realize that a career in science is an option for them.

encourage science education among the IMP students. The idea

In many ways, IMP is an experiment on how to provide extended

to hold a joint event came from Andrew Wong of the Searson lab,

families for at-risk students. Problems are tackled on a trial-and-

an INBT trainee who has been instrumental in IMP’s community

error basis by volunteers from a variety of backgrounds. Often,

Colin Paul, center, watches students making ice cream with liquid nitrogen.

service activities. I led the event, held on February 27, with Charli

an initial solution does not work; but, just like in the lab, we think

Dawidczyk, a doctoral student from the Searson lab.

about what went wrong and try to improve our approach. The

Our first activity was to build a simple speaker using foam

PIs at INBT have encouraged us to make a difference in the com-

plates, magnets, and wire. Students learned how electromagnetic

munity. I’m grateful that my education at Hopkins has included

forces, whose strength and frequency vary depending on the song,

IMP and the wonderful students and volunteers comprising

deflect the foam plate to create sound waves when the plate is glued

the organization.

to a magnet with a coil of wire around it. The speakers weren’t loud, but everyone participated, even though they might have been

Colin Paul is a third-year graduate student at Johns Hopkins Uni-

more interested in the strong neodymium magnets.

versity in the Konstantopoulos lab. He invites anyone with questions

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

24 Johns Hopkins University Nano-Bio Magazine

about or interest in the Incentive Mentoring Program to contact him at colin.paul@incentivementoringprogram.org.

Bringing Hopkins Solutions to the World By Mary Spiro

Global Engineering

“We had to answer

Innovation, a program

many questions,” said