The Magazine of Johns Hopkins Institute for NanoBioTechnology | Winter 2015
Stem Cell Potential Training Across Disciplines
Nano Day!
Stem Cells in 3D!
A closer look
(full page research image and
caption)
Adipose-derived (that is, from fat tissue) stem cells sprout densely connected vascular networks when aggregated into multicellular spheroids prior to fibrin encapsulation. Colors: CD31 (green), alpha-smooth muscle actin (red), laminin (blue). This image comes from the laboratory of Warren Grayson, assistant professor of biomedical engineering at the Johns Hopkins School of Medicine. (http://online.liebertpub.com/toc/tea/19/17-18)
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 http://inbt.jhu.edu Leadership Peter C. Searson DIRECTOR, REYNOLDS PROFESSOR
STORIES
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Stem Cell Advances Highlighted
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I Got My PhD...Now What?
Cells with Potential
at 2014 Symposium
Denis Wirtz VICE PROVOST FOR RESEARCH, ASSOCIATE DIRECTOR, SMOOT PROFESSOR
Staff Ashanti Edwards
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ACADEMIC PROGRAM MANAGER
Tom Fekete DIRECTOR OF CORPORATE PARTNERSHIPS
Boarding the Research Bandwagon
Ellie Boettinger-Heasley
Nanotech Knowledge Shared with Talented Youth
SENIOR ADMINISTRATIVE COORDINATOR
Gregg Nass SENIOR ADMINISTRATIVE MANAGER
Martin Rietveld DIRECTOR, WEB/ANIMATION
Mary Spiro SCIENCE WRITER
ADDITIONAL STORIES 2
Save the Date for Neuro-X
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Letter from the Directors
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Cross-disciplinary Facilities Expand
EDITOR, NANO-BIO MAGAZINE
Photography Lye Lin Lock Mary Spiro Michael Newman (NIST) Will Kirk of Homewood Photography Yi-an Lin Graphic Design Danielle Peterson BRIO DESIGN
ON THE COVER A visual approximation of scientists demonstrating the pluripotency of stem cells. Illustration by Martin Rietveld
LETTER from the DIRECTORS Welcome to the Winter 2015 Nano-Bio Magazine and the ninth year for Johns Hopkins Institute for NanoBioTechnology (INBT) as a University research institute dedicated to creating new knowledge and new technologies to solve problems in health and medicine. Now more than ever, we find the tools that we have created with nanobiotechnology can offer our affiliated faculty and students unique opportunities to answer challenging questions in medicine, engineering and basic science. This fifth edition of the Nano-Bio Magazine showcases some of the Institute’s leading edge research from talks given during our annual symposium, which focused on stem cell technology. You can also read about how our interdisciplinary pre-doctoral education programs have helped prepare our graduates for the job market. We also include a feature story about the Nano-Day for young scientists and engineers, which was coordinated by students from our labs. Peter Searson
The future holds many new and exciting challenges for INBT researchers. We continue to work on solutions that will help diagnose and treat cancer. Questions about the blood-brain barrier remain a top priority for many researchers working in our affiliated laboratories. But we also are moving into new disciplines that we think have not been fully addressed using the tools of nanobiotechnology. On May 2, 2015, we will hold our ninth annual symposium at the Johns Hopkins School of Medicine on the topic of neuroscience. We are calling this symposium Neuro-X, where the X indicates many disciplines in medicine, science, and engineering. Please save the date and join us then! In the meantime, we hope you enjoy this edition of Nano-Bio Magazine.
Peter Searson Director, INBT Denis Wirtz
Reynolds Professor, Materials Science and Engineering
Denis Wirtz Vice Provost for Research Associate Director, INBT Smoot Professor, Chemical and Biomolecular Engineering
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Johns Hopkins University Nano-Bio Magazine
PHOTO BY YI-AN LIN
Stem Cell Advances Highlighted at 2014 Symposium The annual symposium for Johns Hopkins Institute for NanoBioTechnology (INBT) was held May 2, 2014 in the Owens Auditorium on the Johns Hopkins School of Medicine Campus. The theme of the symposium was Stem Cell Science and Engineering and brought together six experts in the area of stem cell research and technology. Graduate student reporters from INBT affiliated laboratories prepared synopses of each presentation. Linzaho Cheng—Human Cell Engineering: Recent Progress in Reprogramming Cell Fates and Editing the Nuclear Genome Linzaho Cheng is a founding member of the Stem Cell Program in the Johns Hopkins Institute for Cell Engineering and the Edythe Harris Lucas and Clara Lucas Lynn Chair in Hematology at Johns Hopkins Medicine. The driving goal for Cheng’s research reads like science fiction. Cheng and his team are working on understanding how stem cell manipulation could lead to a cure for genetic diseases. This cure would follow a conceptually simple but technically challenging chain of events: differentiated somatic cells (that is, fully matured cells) would be collected from the patient, reprogrammed to become induced pluripotent stem cells (iPS cells), genetically engineered to fix the defect, differentiated to a specific cell type in which the defect manifested, and then transplanted back to the patient. With the genetic abnormality fixed, the patient would cease to experience symptoms of the disease. The first three steps in this cure are becoming increasingly attainable. Specifically, Cheng described his team’s progress in generating and editing hematopoietic (blood-derived) stem cells. Because these cells are derived from blood cells, they can be routinely obtained. Cheng’s lab has done pioneering work on the reprogramming of somatic cells into iPS cells, demonstrating that a reprogramming method called
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episome-mediated reprogramming does not create mutations
These challenges drive the need for engineered bone grafts with
associated with cancer development. Furthermore, their work on
anatomical shapes and vigorous blood supply. If these goals can be
editing the genome of iPS cells using CRISPR/Cas9 nucleases
met, patients requiring facial bone grafts will have greatly improved
has shown that the CRISPR/Cas9 procedure is highly specific
outcomes.
and capable of changing a single DNA nucleotide or larger DNA
Warren Grayson is the director of the Laboratory for Craniofacial
segment. Cheng classified these steps as breakthroughs in genetic
and Orthopaedic Tissue Engineering in the Translational Tissue
engineering that can now be implemented even in labs without
Engineering Center at Johns Hopkins Medicine and Assistant
stem cell expertise.
Professor of Biomedical Engineering at Johns Hopkins University.
Ultimately, Cheng hopes to couple these reprogramming capa-
Grayson’s lab is working to engineer bone grafts that become
bilities with the generation of red blood cells and platelets from
incorporated into the blood vessel network of the patient and form
iPS cells for patients that are dependent on blood transfusions. For
intact bone and that are customizable and anatomically correct.
safety reasons, stem cells would most likely not be injected directly
He presented his exciting work on fat cell derived stem cells
for fear of differentiation into cancerous or other non-desirable
at the eighth annual symposium of the Johns Hopkins Institute
cells. Therefore, to complete the vision of a genetic cure, iPS cells
for NanoBioTechnology.
need to be differentiated into the desired cell type before engraft-
To accomplish this goal, the Grayson lab is using adipose-de-
ment in the body. Cheng’s lab has developed a strategy to produce
rived stem cells (ASCs), which are readily available from lipoaspi-
red blood cells from iPS cells in a bioreactor with 10 to 30 percent
rates (the material removed during lipsuction). These ASCs behave
differentiation efficiency. Ongoing work in the lab aims to increase
differentially than bone marrow-derived mesenchymal stem cells in
the efficiency of this process.
a manner that appears to promote blood vessel and bone formation.
Cheng’s presentation began with what he described as a “pro-
The population of ASCs obtained from a patient is heteroge-
vocative” statement—that animal models of human disease aren’t
neous, enhancing differentiation into cell types that form either
good enough, and that well-understood mouse models that have
blood vessels or bone. For example, ASCs expressing a surface
dominated the field for the past 30 years must be improved upon
protein called CD31 are responsible for growing blood vessels.
to advance human health. The take home message from his work,
Grayson and his team have demonstrated that when ASCs are
however, may be even more provocative. If physicians and engi-
treated with platelet-derived growth factor (PDGF), the generation
neers can control the genetic code of an individual’s cells, genetic
of blood networks is further increased. After vessels form, ASCs
diseases may one day be a thing of the past.
that have differentiated to bone forming cells lay down the mineral
—Colin Paul
building blocks of bone, using the vessels as a kind of template. Therefore, ASCs that are properly treated with PDGF are capable Warren Grayson—Regenerating Musculoskeletal Tissues from Fat
of producing the precursors of healthy bone. With this promising knowledge of the cues that ASCs need to develop, Grayson’s lab is now engineering a scaffold to deliver the
Each year hundreds of thousands of
cells and platelet-derived growth factor to the site of injury. By
medical procedures require bone grafts
using polycaprolactone, a biodegradable polymer, in a 3D printer,
to the skull. Traditionally, these grafts
Grayson’s team can construct anatomically correct scaffolds in
are performed by breaking up the
which ASCs can differentiate into vascularized bone. Using the 3D
fibula and trying to reconstruct the
printer, a scaffold in the shape of a jaw or nasal cavity can be made
bone structure of the skull.
to accommodate a patient’s specific injury.
Because the skull dictates facial features, this process is extremely
The scaffold is initially coated with a hydrogel amenable to cell
important to patient appearance and function. But the process of
growth. Following a period of cell growth and vascular differentia-
reconstruction comes with challenges. Imagine trying to build a
tion in the lab, these scaffolds can be implanted. Grayson’s lab has
human jaw from an inflexible cylinder.
already demonstrated that cells implanted in these scaffolds can
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Johns Hopkins University Nano-Bio Magazine
PHOTO BY YI-AN LIN
survive implantation into mice and maintain structural integrity,
Linda Resar—Hitting the
both in the scaffold and in the cell-formed structures formed
Bull’s Eye: Targeting HMGA1
within. Their work on scaffold engineering was recently published
in Stem Cells for Cancer Therapy
in the Journal of Biomedical Materials Research Part A.
or Regenerative Medicine
Grayson’s exciting work innovatively combines stem cell and
using Nanotechnology
biomedical engineering. They are now working to incorporate “oxygen tanks” into their scaffolds to increase oxygen transport to
Linda Resar is internationally recog-
the cells and further improve cell survival. These advances hold
nized for pioneering studies on the role
great promise for musculoskeletal regeneration from accessible and
of High Mobility Group A (HMGA)
abundant stem cell populations.
proteins in cancer. In 1992, she received an American Society of
—Colin Paul
Clinical Oncology Young Investigator Award and was recruited to the faculty of the Johns Hopkins University School of Medicine.
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Resar is board certified in Pediatric Hematology/Oncology and
It is critical to find methods that control this differentiation into
is an attending physician in the Hematology Clinic at the Johns
a desired specific cell type for the application of interest. Interestingly, nanotechnology methods have shown great promise
Hopkins Hospital. Resar’s research provides great promise for blocking progression
in overcoming these challenges. Specifically, combining topographical
of cancer. Her talk focused on a family of proteins termed “high
cues, such as engineered nanofibers, with biochemical growth factors
motility group A1.” These small proteins alter chromatin structure
can greatly increase efficiency of desired differentiation.
in the nucleus and thus regulate transcription of proteins. A particular gene encoding for these proteins, HMGA1, is
Mao’s group has prepared electrospun fibrous scaffolds that highly resemble the body’s natural extracellular matrix. These scaffolds
enriched in stem cells of embryonic development as well as in
have proven successful in enhancing stem cell survival in addition
poorly differentiated cancers. In fact, the gene’s expression strongly
to directing specific stem cell fates. In another fascinating study,
correlates with poor prognosis in cancer. For instance, cancer
Mao collaborated with the laboratory of INBT affiliate Sharon
cells derived from the most metastatic cancers exhibit the highest
Gerecht, associate professor of chemical and biomolecular engi-
expression levels of HMGA1.
neering, in the development of a novel three-dimensional fibrin
Additionally, patients who relapse after cancer treatment tend to have high levels of the gene, and patients with the highest expres-
microfiber scaffold to engineer a small blood vessel. ~Allison Chambliss
sion levels have the lowest survival probability. HMGA1 also may drive a cancer stem cell phenotype. Consequently, there is hope
Mark Powers—Engineering Human
that targeting the gene may lead to the discovery of effective cancer
Pluripotent Stem Cells for Disease
therapeutics. In breast cancer cells, silencing the gene induced a more
Modeling and Applications:
normal breast cell phenotype and prevented metastatic progression.
Perspectives from a Tools Provider As Senior Director of Research and
Resar is currently working on an exciting collaboration with INBT affiliated professor Justin Hanes from the Johns Hopkins
Development for Cell Biology at
School of Medicine to develop a nanoparticle delivery method that
Thermo Fisher Scientific, Mark Powers
would block HMGA1 activity.
gave a vivid introduction about how
~Allison Chambliss
the R&D group in this top biotechnology company supports bioengineering research and society. His Hai-Quan Mao—Engineering
lecture showed the effort Powers’ research term made to develop
Biomaterials to Enhance
more reliable reagents, optimize the conditions, and help in hands-
Stem Cell Potential
on education and training for researchers.
Hai-Quan Mao is a professor
others to build a human induced pluripotent stem cell model of
of materials science and engineering
Parkinson’s disease (PD) in a dish to elucidate the molecular basis
at Johns Hopkins Whiting School
of PD and to identify compounds that impact disease phenotypes.
of Engineering and an INBT affiliated
They took fibroblast biopsies from the patients, derived iPSC lines
faculty member. He opened his talk
using Sendai viral vector, performed TALEN-based gene editing
Powers also gave an example of the company’s collaboration with
by explaining several of the biggest technical hurdles that often
and correction on alpha-synudein and LRRK2 genes, and then
prevent translation of stem cell-based therapies.
differentiated the iPSCs into neuron stem cells to measure the
One such obstacle is cell delivery. Implementing a stem cell therapy to a new source can have risks, and methods must be developed that increase cell survival while preventing inflammation and scar formation.
PD-related phenotype and the pharmacological rescue with known effective drugs. All the key reagents and kits used in the experiments were from
Another major obstacle is the cell source. Stem cells are pluripotent,
the company’s own product catalog in order to stand in the cus-
meaning they have the capability to progress into several cell types.
tomer’s shoes to find any defects and make improvements. Powers
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Johns Hopkins University Nano-Bio Magazine
said he believed that by doing this his team would not only be able
Writers
to contribute their findings to the PD study, but also to take the
Allison Chambliss recently completed her PhD under Denis Wirtz
challenges and opportunities that occur along the entire workflow
in the Chemical and Biomolecular Engineering Department. She is
of pluripotent stem cell research and provide better products and
now a clinical chemistry postdoctoral fellow with the Department
service to customers.
of Pathology at the Johns Hopkins Hospital.
—Ying Wang Colin Paul is a fifth-year PhD student in the laboratory of Konstantinos Guo-li Ming—Understanding the function of risk genes
Konstantopoulos in the Department of Chemical and Biomolecular
for mental disorders using iPSC
Engineering and Institute for NanoBioTechnology. His thesis project
model
examines tumor cell migration in engineered microenvironments.
Guo-li Ming is currently a professor at
Ying Wang is currently a fifth-year PhD student in Sharon Gerecht’s
the Institute for Cell Engineering the
lab in the Chemical and Biomolecular Engineering Department,
Johns Hopkins School of Medicine.
co-advised by Dr. Linzhao Cheng in the Institute for Cell Engineering
Her work focuses on the mechanisms
in the Johns Hopkins School of Medicine.
of neurological diseases arising from aberrant neural development and circuitry formation. Ming’s lecture detailed the courageous, ongoing research into schizophrenia, one of the most common and devastating psychiatric diseases with neural developmental origin affecting about 1 percent of the population in the U.S. She described their study in a familial mutation in Disrupted-In-Schizophrenia 1 (DISC1) gene locus, which is involved in multiple psychiatric disorders and cognitive disorders. Four patients from the same family were studied who shared the unique four base pair deletion in the DISC1 locus and developed schizophrenia. Patients’ fibroblasts were reprogramed into iPSC lines. All these cell lines showed a heterozygous mutation in one allele. Using these iPSC lines, Ming’s group generated forebrain specific neural progenitor cells (NPCs)—cortical neuronal subtypes—that represented the phenotype of schizophrenia. The results showed that the neural progenitor cells with the DISC1 mutation showed defects in the morphological development, decreased density of SV2+ synaptic boutons, defects in presynaptic vesicle release, and decreased glutamatergic synaptic transmission. They also performed TALEN-induced gene correction and mutation correction, looking for the recovery of phenotype. Based on the gene expression changes in disease cell lines, they found that many upregulated genes actually were proved to be involved in various mental disorders.. Ming said she hopes their studies of the mechanism of schizophrenia can shed light on potential therapeutic targets for correcting synaptic defects to cure schizophrenia. —Ying Wang
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10 Johns Hopkins University Nano-Bio Magazine
I Got My PhD... Now What? BY ALLISON CHAMBLISS AND MARY SPIRO
On the National Science Foundation’s website, there is a definition
What could help a graduate student stand out among others
of interdisciplinary research; but there is also one caveat: “What is
is an interdisciplinary training background that spans multiple
considered interdisciplinary today might be considered disciplinary
scientific areas. Johns Hopkins Institute for NanoBioTechnology
tomorrow.” With this in mind, Johns Hopkins Institute for
paves the way for innovative ways to approach these challenges
NanoBioTechnology is at the forefront of interdisciplinary training
in graduate education. Students associated with INBT’s Nano-Bio
methods, creating a template to keep up with these continually
Graduate Training Programs are provided with a needed advantage
emerging new “fields” of study.
through interaction with cross-departmental co-advisors and re-
However, many universities still cling to a thesis-based graduate training model, which can be very topic-specific and prove to be limiting for new PhDs ready to get a jump on the job market.
search collaborators, as well as a slew of unique training courses in everything from laboratory techniques to communication. Only a few extra courses beyond the departmental requirements
Doctoral students often spend five or more years deeply examin-
for a PhD are necessary to complete the Certificate of Advanced
ing a narrow research topic, only to find that companies and other
Study in Nanobiotechnology developed by INBT. They include
academic institutions are looking for scientists to work in vastly
two courses specific to nanobiotechnology, a course in advanced
different areas. Indeed, the true value of the doctorate degree is not
cell biology, a weekly journal club, nanobio tutorial workshops and
necessarily in becoming an expert in a specific research area, but
a course in communication. And the testimonies of the impact of
more in developing the logical and critical thinking skills and col-
this extra training from students who have been through the pro-
laborative attitudes required to succeed in any scientific field.
gram are powerful. Alumni and current students attest to the fact
Winter 2015 11
Angela Jimenez
that INBT’s interdisciplinary training both accelerates scientific
Craig Copeland
In the process, Angela has gained new knowledge that she
discovery and creates the most prepared and experienced scientific
wouldn’t have otherwise obtained from day-to-day experiences
researchers.
in the Wirtz Lab. “I was excited to learn about the dynamics of collaboration and how to work with people from different cultural
Collaboration offers discovery insight
and scientific backgrounds, as well as what types of projects are
Angela Jimenez, is a nano-bio training grant graduate student in
interesting and important to model mathematically.”
the lab of Denis Wirtz, professor in the Department of Chemical
What’s more, those perks won’t end once Angela finishes her
and Biomolecular Engineering and also vice provost for research
PhD. “All of these skills will benefit my career, regardless of what
for JHU. Angela is interested in measuring tumor growth in a
path I choose to pursue after I graduate,” she added.
novel three-dimensional cell culture system. Her experiments seek to define the relationship between invasiveness of cancer cells and
Journal clubbing into the job market
the dense collagen matrix that surrounds them, with hopes that
Kate Malachowski, a 2013 graduate of INBT from the lab of
this insight could potentially develop therapeutics to stop cancer
David Gracias, also an affiliated faculty member and professor in
from metastasizing.
the Department of Chemical and Biomolecular Engineering, has
But Angela’s experiments can only look at a few biological
seen first-hand how an interdisciplinary background can propel a
conditions out of hundreds of possible scenarios within the body.
career. Through INBT, Kate developed a collaborative relationship
Angela’s co-advisor, Sean Sun, an INBT affiliated faculty member
with Northrop Grumman, a large aerospace and defense contract-
and professor in the Department of Mechanical Engineering, has
ing company who provided her with a multi-year corporate spon-
helped Angela expand her experimental data into a mathematical
sored fellowship during her time as a Hopkins graduate student.
model that, with the input of a few parameters, could be valid to
INBT’s Director of Corporate Partnerships, Tom Fekete, facilitated
characterize cancer cell movement for any desired condition.
this fellowship.
“There are experiments that are not feasible except through
Kate’s fascinating project combined microfabrication and
modeling, so the collaboration helps us gain further insight into
engineering principles with medical expertise to create novel
what is going on within the tumors,” explained Angela.
“microgripper” surgical tools. She credits much of what she learned during her graduate years to INBT’s biweekly journal club.
12 Johns Hopkins University Nano-Bio Magazine
PHOTO BY MARY SPIRO; RIGHT: PHOTO BY MICHAEL NEWMAN (NIST)
Kate Malachowski
“Having the opportunity to meet biweekly allowed me to bounce
physics training, my biology/bio-engineering training, or both. In
ideas and brainstorm with peers who had diverse skill sets and
particular, when interviewing for my current position, I spent the
knowledge bases,” she said. Kate now works full-time at Northrop
day meeting with various members of the Center for Nanoscale
Grumman. Although her current work is based on the company’s
Science and Technology and found it surprisingly easy to talk sci-
electronics programs, she is eager to use her interdisciplinary knowledge
ence with folks working in a broad range of research areas.”
in order to introduce novel biological applications to these projects.
Craig also noted that interdisciplinary training provided valuable opportunities to learn things far beyond scientific facts from other
Broader understanding leads to better opportunities Students from disciplines outside of engineering are also attracted
areas of science. “Not only the laboratory techniques required for biological
to the benefits of INBT’s multidisciplinary graduate training
work, but also problem solving techniques, teaching methodolo-
programs. Applicants for the Certificate of Advanced Study in
gies, and the simple broadening of my scientific vocabulary have
NanoBioTechnology come from several departments in the Krieger
all proved quite valuable to me; the latter especially with all the
School of Arts and Sciences, School of Medicine and even from the
attention that biological systems are currently getting,” he said. “I
Bloomberg School of Public Health.
believe that having an open mind and a flexible willingness to learn
In 2013 Craig Copeland earned his PhD in Physics in the laboratory of Daniel Reich, professor of Physics and Astronomy.
are valuable attributes for any professional, and my INBT training allowed me to gain experience putting these qualities to work.
He is now a postdoctoral researcher at the National Institute for Standards and Technology Center for Nanoscale Science and
Allison Chambliss recently completed her PhD under Denis Wirtz in
Technology. Craig is developing optical microscopes and methods
the Chemical and Biomolecular Engineering Department. She is now
for tracking nanoparticles as indicators of the motion of microme-
a clinical chemistry postdoctoral fellow with the Department of Pathol-
chanical and nanomechanical devices.
ogy at the Johns Hopkins Hospital.
“My interdisciplinary education has certainly been an asset moving beyond graduate school,” Craig said. “I was quite comfort-
Mary Spiro is INBT’s science writer and media relations director.
able looking for positions that required experience from either my
PHOTO BY WILL KIRK
Winter 2015 13
Adipose (fat tissue)-derived stem cells undergo vascular morphogenesis when seeded at high density and in the presence of angiogenic factors.Vessels express CD31 (green) and are surrounded by pericyte-like cells expressing alpha-smooth muscle actin (red). Nuclei are counterstained with DAPI (blue). This photo was created by Warren Grayson laboratory, assistant professor of biomedical engineering at the Johns Hopkins School of Medicine. (http://online.liebertpub.com/toc/tea/18/15-16)
Cells with Potential BY REZINA SIDDIQUE
Stem cells, cells in the body that can develop into practically any
and the Lucas and Lynn Chair in Hematology. Cheng has been at
tissue or organ, have been heralded for their potential therapeutic
the forefront of stem cell technology for more than 20 years, and
qualities to treat disease, but they are rare and difficult to expand.
can shed light on the history of stem cell medicine at Johns Hopkins.
Human embryonic stem cells that are made from early embryos,
In 1991, Cheng received his Ph.D. in Molecular Biology and
full of potential (called pluripotent) and able to expand in the labo-
Genetics from the Johns Hopkins School of Medicine, where he
ratory, however, carry some scientific as well as ethical concerns.
worked on human DNA replication models and transcriptional
In 2006, a group in Japan developed a method to generate what
factors, including one of the first two DNA-binding proteins from
are called “induced pluripotent” stem cells (iPSCs) using mouse skin
mammalian cells (NF-I/CTF), and published landmark papers in
cells. Before long, these engineered stem cells were being created by
Cell and PNAS. The young researcher was drawn to the emerging
genetically modifying human adult skin or blood cells. They also
field of stem cell technology.
exhibited exhibit the same qualities as embryonic stem cells. Johns Hopkins University researchers have a long history of con-
Before joining the Johns Hopkins faculty, he was exposed to the challenges of researching stem cells in industry and in NIH.
tributions to stem cell technology. One of the university’s leaders
Cheng’s stem cell research career started as a postdoctoral fellow
in the field is Linzhao Cheng, professor of Medicine and Oncology
helping to establish the mouse pluripotent stem cell lines from pri-
and a founding member of the Stem Cell Biology Program at the
mordial germ cells, which was published in Nature in 1992. Since
Johns Hopkins Institute for Cell Engineering. He is also the As-
1994, his research has focused on human stem cell biology and
sociate Director for Basic Research in the Division of Hematology
cell engineering after he joined a pioneering stem cell company.
14 Johns Hopkins University Nano-Bio Magazine
However, one of the issues with these types of cells
Cheng joined the Johns Hopkins faculty in 1999 and received the Presidential Early Career Award for Sci-
is something called epigenetic memory, which means
entists and Engineers in 2003. In 2012, Dr. Cheng
that genetic information outside of the DNA strand
was elected as a Fellow of the American
persists. This can affect how the genes within the
Association for the Advancement of Sciences (AAAS).
DNA are expressed in future cultures of these cells. These epigenetic memories can be negative or they can
Cheng says his early work in stem cells helped to cement his perspective that, “Good science should
also be positive but become particularly relevant in
not only be beautiful, but also useful.” He learned
cloning studies.
to approach science with the mindset of using it as a
In Cheng’s stem cell laboratory, the focus is on
tool to solve real world problems. In his lab, Cheng
blood disease modeling and its treatment. They use induced pluripotent blood stem cells to develop appli-
believes in integrated versus discrete research, and has a multidisciplinary team consisting of both biologists and
cations for blood disease. Fortunately for Cheng and his colleagues,
engineers, including a PhD student Ying Wang who is from
blood cells have a fairly low rate of mutation as compared to cell
Department of Chemical and Biomolecular Engineering.
types exposed to sunlight and environmental toxins. There is also a
In 2002, Cheng helped found the Johns Hopkins’ Stem Cell Biology Program in the then newly formed Institute for Cell Engineering. The program has two goals: first to understand how stem
relatively unlimited supply of blood cells from the patient or their best match. The precise genetic engineering used to create iPSCs allows for
cells work and second, to find ways to use stem cells as tools to treat
tailored disease modeling and drug screening. Where previously
human disorders. But before long, he realized that working with
animal models were used and researchers tried to focus on the simi-
human stem cells was a lengthy process. To avoid the ethical, regu-
larities instead of the differences, induced pluripotent stem cells
latory, and practical constraints involved with using human em-
from blood allow for more elaborate and precise modeling using
bryonic stem cells, researchers were beginning to seek alternatives.
human cells to study humans, Cheng explained.
Then in 2006, researcher Shinya Yamanaka at Kyoto University in
Despite their advantages, using induced stem cells is not without
Japan developed the first “induced” pluripotent stem cells (iPSCs).
challenge, Cheng said. “For example, even induced stem cells can
Yamanaka later won the Nobel Prize for Physiology or Medicine
have complications comparable to adult human stem cells. For
in 2012 for his stem cell discoveries.
example, iPSCs as well as embryonic stem cells can form teratoma
Induced means that cells that are not originally stem cells, but other tissue cells, are genetically modified to behave like stem cells.
(a benign tumor composed of multiple tissue types generated from pluripotent cells),” he said.
Induced pluripotent stem cells can be developed from adult cells by
In the short term, such complications may shift in the way
introducing a set of genes into a particular cell type. As pluripotent
research on disease and drug testing is performed with induced
stem cells, they have the powerful ability to propagate indefinitely
stem cells. But in the long term, iPSC-based research can lead to
and can be induced to become any other type cell in the body:
regenerative therapies, such as cell transplantation and transfusion.
from to blood to neurons to tissue.
The Cheng lab is actively working on generating large numbers
Cheng recalls attending a lecture where induced pluripotent stem
of red blood cells from human iPSCs in the laboratory. This may
cells were first discussed. “They described inducing pluripotency as
provide a new solution for transfusion-dependent patients who
essentially reversing the biological clock of a cell within a test tube,” he said.
developed immune rejection to a donor’s red blood cells and lack
The procedure of introducing the pluripotency genes was first
other alternatives for obtaining needed red blood cells. Through an
performed successfully in mice, followed by humans, as is often
integrated, multidisciplinary approach, Cheng said, he expects the
the case with biological research. Using only a few drops of human
induced pluripotent stem cell technologies to have a bright future
blood, scientists were able to create stem cells nearly identical to
with many potential therapeutic applications.
embryonic stem cells. Rezina Siddique earned her Ph.D. in biomedical engineering at Johns Hopkins University.
Winter 2015 15
Cross-disciplinary Facilities Expand BY MARY SPIRO
Croft Hall on the Homewood campus houses the headquarters for
Hristova and Martin Ulmschneider from Materials Science and
Johns Hopkins Institute for NanoBioTechnology. INBT offices
Engineering; and Feilim Mac Gabhann from Biomedical Engineer-
and laboratories have occupied most of the building except for the
ing and the Institute for Computational Medicine.
second floor, which, up until a couple of months ago, had been
Along with lab and office space, there will be an imaging core
used for offices in the computer science department. Now INBT
composed of a suite of specialty microscopes managed by the
is set to expand once more to create a highly interdisciplinary and
Integrated Imaging Center (IIC) led by Michael McCaffery, whose
flexible environment for nanobio research.
main facilities are located in Dunning Hall on the Homewood campus. Student office space and gather-
In total, the renovation creates a little more than 12,500 square feet of space for INBT use in both Croft and Shaffer Halls.
ing areas are also part of the plans. In total, the renovation creates a little more than 12,500 square feet of space for INBT use in both Croft and Shaffer Halls. “This expansion will establish a vibrant community for nanobiotechnology
By the fall of 2015, new facilities for a group of INBT affiliated faculty members will open on the second floor of Croft Hall and also encompass part of Shaffer Hall. The new space allows INBT
research and education for INBT affiliated faculty, students and staff,” said INBT director Peter Searson. The faculty members involved in the expansion all have primary
to continue as a model for integrated research and education at
lab and office space in their respective departments, noted Searson.
Johns Hopkins, and will further enhance INBT’s reputation and
But by providing these researchers with secondary laboratory
visibility. The expansion includes laboratory space for two faculty
spaces, Searson added, “we will be able to leverage their comple-
members from the Johns Hopkins School of Medicine, Martin
mentary expertise and further our commitment to interdisciplinary
Pomper, MD, PhD from Radiology and Oncology and Laura
research, as well as generate new resources for the Whiting School
Wood, MD, PhD from Pathology and Oncology, both of whom
of Engineering and the University as a whole.”
are contributing to ongoing INBT programs. In addition, INBT will house laboratory space for five engineering faculty including Sean Sun and Jeff Wang from Mechanical Engineering; Kalina
16 Johns Hopkins University Nano-Bio Magazine
Watch the INBT blog for updates on the renovations as they occur at this link http://inbt.jhu.edu/blog.
Boarding the Research Bandwagon BY PRANAY TYLE
Pranay Tyle (left) credits his laboratory mentor Hasini Jayatilaka as being a key to his undergraduate research success.
PHOTO BY MARY SPIRO
Winter 2015 17
The story of how I joined Johns Hopkins Institute for NanoBio-
The best part of being involved in research, apart from the work
Technology (INBT) is actually one of those moments where it
you do, is sitting in class in a lecture hall and suddenly tune in to
just hits you – Why haven’t I thought about doing this before?
the professor talking about something that you do in lab each day.
It started with me being back at home during the winter of my
That moment cements your understanding of why you did what
sophomore year, meeting friends of my parents and answering the
you’ve been doing for so many days, it connects the dots in your
most common question: Where do you study? One of the reactions
mind, and that moment is when you’ve completed the full circle
that stuck with me the whole night was “Wow, how does it feel to
between theory and practice.
be in the center of the most cutting-edge research?” This made me
For me personally, having to come to lab got me into a disci-
realize how I’d been oblivious to one of the things I would love to
plined schedule. I had a fixed time for all days of the week now to
get involved in.
wake up (which for me used to be the latest possible time), since if
Better one and a half years late than never, I decided to join the
I had no morning classes, I was in lab. It helped me a lot with my
research bandwagon as well. I started going through the profiles of
time management skills, with me cutting down on TV shows and
labs on Homewood campus, looking for a topic that would make
sporadic naps. To my surprise, it did not affect the amount of time
me want to be there in lab every free minute during the year. I
I spent with my friends, as the reduction in TV shows and naps
finally found one that sparked my curiosity: the Denis Wirtz Lab.
was (extremely) disturbingly enough to keep every other aspect of
Dr. Wirtz is the Smoot Professor in the Department of Chemi-
my daily schedule the same. Being surrounded in lab by people in
cal and Biomolecular Engineering and also the University’s Vice
similar academic disciplines also gets me a ton of advice on classes.
Provost for Research.
It’s like my own little “rate-my-professor” that encourages me to
Though at the time most of the stuff I read about the Wirtz lab
definitely take some class if it is “the best class I will take at Hop-
went over my head, I knew that cancer was something I had always
kins”. At times, it’s also a ‘learning den’ where I can get help with
wanted the world to be rid of. Seeing near and dear ones succumb
classes if I need to. Getting involved in a research lab also came
to it was one of the most excruciating things which I wanted no
with social outings with the team, with our dinners enabling us to
one to experience in the future. Fascinated by the approach taken
get to know each other on a more personal level. I feel that this in a
by Dr. Wirtz, I shot him off an email and to my amazement, I got
big way contributed to the chemistry we have while working with
an email back within the hour, “Sent to my grad students, look
each other, made us comfortable spending time with each other at
forward to working with you.” The next day I was scheduled to be
work.
back in Baltimore, and the day after that, I was a part of Wirtz lab. During my training, I remember asking one of my peers “How
At this point, after nine exciting months, including a fully lab-packed summer, I feel that this continues to be one of the
in the world can I remember all these procedures, let alone do
best decisions I made so far. I do not regret being here every day,
them?” She simply smiled and said, “You’ll see.” In a few weeks, I
but take pride in saying “I need to be in lab.” One of the most
found myself doing those very procedures, one step after another as
cherished take-away for me is developing a sense of accountability
if it were a reflex action. I would most definitely attribute me being
for my actions, which I feel is an important aspect in life. I would
able to do this to my grad student Hasini Jayatilaka. At the end of
definitely encourage being involved in research while at Hopkins as
the day, what I felt it boiled down to, was realizing that the person
you have nothing to lose but so much to gain.
I work for was in the same shoes five-seven years ago as I was now, and she wouldn’t expect anything unrealistic out of me. Once you
Pranay Tyle, is a junior in Chemical and Biomolecular Engineering
embrace the challenge ahead, knowing that there is no need to be
minoring in Economics, and hopes to one day manufacture low cost
intimidated, you’re good to go.
medicine accessible to those in dire need across the globe.
18 Johns Hopkins University Nano-Bio Magazine
Assistant Professor Chao Wang demonstrates renewable energy project.
Nanotech Knowledge Shared with Talented Youth BY MARY SPIRO
PHOTO BY LYE LIN LOCK
Winter 2015 19
Plant-based solar cells.
Assistant Professor Honggang Cui helps a CTY student in nano-drug delivery project.
One way to encourage more kids to be interested in science and
“This clinically relevant experiment demonstrated how some
engineering is to offer them fun ways to learn about it. Johns
chemotherapy drugs need an extra ingredient to make them more
Hopkins Center for Talented Youth creates such opportunities
soluble, and therefore, more effective in treating cancer.” Zhang
throughout the year. Students and postdoctoral fellows from Johns
said. “Many cancer drugs have poor solubility and this is a big issue
Hopkins Institute for NanoBioTechnology-affiliated laboratories
for biomedical applications. Since many molecules do not dissolve
recently had the chance to help budding young scientists and engi-
very well, we have to use a carrier, in this case a surfactant, to make
neers by developing hands-on projects for CTY’s nanotech day.
them dissolve. We used a model molecule that is similar to a cancer
The event, “Small is Big: Using Nano-Sized Objects to Address
drug and compared how well the molecules dissolved with and
Global Problems,” offered five different nano-related projects for
without the surfactant. With the surfactant, it remained stable and
middle school aged children (and their curious parents) to try
in solution much longer.”
out. Project leaders came from the laboratories of professor David
Zhang said a clear color change associated with the experiment
Gracias, and assistant professors Honggang Cui and Chao Wang
made it easier to mark results. If the molecule did not dissolve, the
from the Department of Chemical and Biomolecular Engineering;
particles remained bright yellow. If the molecules dissolved, the
Michael McCaffery, director of the Integrated Imaging Center;
solution became bright green.
and Beverly Wendland, professor of Biology and acting dean of
“The kids were not really familiar with basic science, so you had
the Krieger School of Arts and Sciences. Project topics included
to tell them everything from the beginning,” said Ran Lin, one of
designing nanomedicines, nano-enabled renewable energy, micro-
Cui’s predoctoral students who helped lead the project. “But they
and nano-patterning, using fluorescence in biological imaging and
were really curious. Some of the parents were even more curious
Mendelian genetics. Groups of students and their parents rotated
about the projects because they had had experience working in
through each project that was set up in various locations on the
laboratories.” Another graduate student from the Cui lab who
Homewood campus.
helped present the experiment to the students, Lye Lin Lock, took
The project on nanomedicine from the Cui lab, which was
photos throughout the day (shown here).
developed by postdoctoral fellow Pengcheng Zhang, used a simple chemistry experiment to drive home its message.
20 Johns Hopkins University Nano-Bio Magazine
PHOTOS BY LYE LIN LOCK
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