UMD Fischell Department of Bioengineering 2017-2018 Year in Review

A. James Clark School of Engineering

ACADEMIC YEAR IN REVIEW: 2017-18

THE FISCHELL DEPARTMENT OF BIOENGINEERING

UNIVERSITY OF MARYLAND / FEARLESS IDEAS

THE FISCHELL DEPARTMENT RESEARCH TEAM DEVELOPS BREAKTHROUGH
OF BIOENGINEERING TECHNIQUE TO COMBAT CANCER DRUG RESISTANCE

Established in 2006 The ability for cancers to develop resistance to chemotherapy drugs – known as multidrug
resistance – remains a leading cause for tumor recurrence and cancer metastasis.
RESEARCH EXPENDITURES BY
SPONSOR FOR 2017-2018: New findings put forth by University of Maryland
National Institutes of Health Fischell Department of Bioengineering (BIOE)
Professor Xiaoming (Shawn) He and researchers
$5.31 million from five other academic institutions point to a
National Institute of Standards and technique that uses specially designed nanoparticles
Technology and near infrared laser treatment to cause cancer
cells to lose their multidrug resistance capabilities
$3.12 million for days at a time.This creates a therapeutic
National Science Foundation window for chemotherapy to combat even the
most drug-resistant cells left behind after surgery
$1.65 million or earlier treatment.The group’s findings were
Nonprofit & Individuals published in Nature Communications.

$1.53 million “By administering chemotherapy within this DR. XIAOMING (SHAWN) HE
Designated Research Initiative Fund ‘therapeutic window,’ oncologists could apply a
lower dose of chemotherapy drugs to patients,
$836,000 with the potential for an improved treatment
Department of Defense outcome – all while minimizing drug toxicity to
healthy organs,” He said.
$647,000
State One of the primary reasons cancer cells develop resistance is the overexpression of what
are known as efflux pumps – proteins that protect a cell by pumping out unwanted toxic
$510,000 substances before they can reach their intended target. In the same way that efflux pumps work
Industry hard to protect against toxins, they also expel virtually all clinically relevant chemotherapy drugs.

$379,000 Fortunately, efflux pumps require a source of chemical energy to perform their function.
Food and Drug Administration As such, by cutting off the energy supply to the efflux pumps, oncologists could lower – or
even eliminate – a cell’s resistance to drugs, such as those administered for chemotherapy.
$97,000 Recognizing this, He and his research team developed a way to reduce the amount of chemical
Department of Agriculture energy – adenosine triphosphate (ATP) – available to the efflux pumps in cancer cells.

$30,000 The team – which also included researchers from The Ohio State University, University of
Virginia, University of Missouri School of Medicine, Shanghai University of Traditional Chinese
TOTAL: $14.1 MILLION Medicine and Indiana University School of Medicine – targeted a specially designed nanoparticle
to the mitochondrion, the cell’s power generator wherein the cell converts oxygen and
Cover photo by John T. Consoli (UMD) nutrients into ATP. Once the nanoparticles reach the cancer cells’ mitochondria, the researchers
apply near infrared laser treatment to trigger a chemical reaction that reduces the amount of
ATP available to the pumps and, thus, cuts off their power supply. Such treatment both reduces
the expression of the efflux pumps and decreases their distribution on the cell plasma membrane.

He and his team assembled a unique lipid membrane-coated silica-carbon hybrid nanoparticle
capable of targeting mitochondria through pyruvate, a chemical compound naturally used
by cells to produce energy in the mitochondria. Using near infrared laser irradiation, He and
his team were able to trigger the nanoparticle to produce reactive oxygen species that could
oxidize NADH – an enzyme that is essential for cell metabolism in mitochondria to generate
ATP – and thereby halt production of ATP and cut off the power supply to the cell’s efflux
pumps. Furthermore, such treatment can reduce the expression of the efflux pumps and decrease
their distribution on the cell plasma membrane.

The research team’s findings demonstrate that the drug-laden nanoparticles – in combination
with near infrared laser treatment – can effectively inhibit the growth of multidrug-resistant
tumors with no evident systemic toxicity.While researchers have long worked with nanoparticles
for drug delivery, the findings put forth by He and his team represent a crucial breakthrough in
addressing multidrug resistance in cancer cells.

Dr. Xiaoming (Shawn) He was inducted into the American Institute for Medical
and Biological Engineering (AIMBE) College of Fellows in 2018.

THREE PROFESSORS AWARDED NATIONAL INSTITUTES OF HEALTH
RESEARCH PROJECT GRANTS (R01) IN AS MANY MONTHS

Three University of Maryland Fischell Department of
Bioengineering (BIOE) professors each received a National
Institutes of Health (NIH) Research Project Grant (R01)
between the months of February and April.The awards,
which collectively total $5.3 million, will support research in
the areas of immunology, optics, and biotherapeutics.

BIOE Associate Professor Christopher Jewell was awarded
a four-year, $1.4 million NIH R01 for his efforts to study the
immunology behind autoimmune disease and develop new
advanced therapies for diseases such as multiple sclerosis (MS).

Assistant Professor Giuliano Scarcelli was awarded a five-
year, $2 million NIH R01 towards developing an optical
technology that could improve diagnosis and management of
keratoconus, a progressive eye disease that often begins during
a person’s teens or early 20s.

Assistant Professor Steven Jay was awarded a five-year, $1.9 DRS. GIULIANO SCARCELLI, CHRISTOPHER JEWELL, AND STEVEN JAY
million NIH R01 award to investigate a new approach for
treating non-healing wounds using cell-derived structures cornea] as early as possible, current imaging techniques only assess the
known as exosomes. shape of the cornea and not corneal biomechanics.This leaves doctors
and patients with limited information when diagnosing keratoconus,
Advancing autoimmune disease research or when planning surgeries.

Autoimmune disease causes the body to identify its own “self ” cells To overcome current corneal screening limitations, Scarcelli and
as foreign and, in response, the immune system attacks healthy tissue. members of his Optics Biotech Lab have applied their own optical
In MS, the immune system incorrectly recognizes components of technique, known as Brillouin microscopy, to measure corneal
the central nervous system, causing inflammation and destruction of stiffness at a high three-dimensional resolution, without contacting or
myelin, the fatty substance that surrounds and protects nerve fibers. perturbing the eye.
When this happens, nerve fibers and cells are damaged, leading to a
loss of motor function and other complications. With support from the NIH, Scarcelli and clinical collaborator Dr.
J. Bradley Randleman of the University of Southern California will
To lessen the immune system’s attack against self cells, conventional work to validate Brillouin measurements for mechanical evaluation of
therapies rely on general immune suppression – a strategy that has the cornea, and characterize observed changes in cases of keratoconus.
proven effective, but can leave patients susceptible to disease or Moving forward, they also hope to determine the mechanical impact
infections. of refractive surgery on the cornea.

To explore new pathways toward MS treatments that would leave New approaches for treating non-healing wounds
the patient’s immune system intact, Jewell, collaborator Dr. Jonathan
Bromberg (University of Maryland School of Medicine Professor Exosomes are a type of small extracellular vesicle – ubiquitous,
of Surgery and Microbiology and Immunology), and the rest of his biologically-generated structures that naturally transfer nucleic acids
team are using degradable biomaterials and combinations of immune between cells. Decades ago, researchers believed that exosomes did
signals to study how local changes to the function of lymph nodes – the little more than offload cellular waste.Today, however, exosomes are
tissues that determine how immune responses develop – could affect better understood as “messengers” that carry out a range of important
the body’s ability to defend against foreign invaders while inflicting cellular functions such as the transfer of DNA, RNA, and proteins
minimal harm to itself. to other cells, where they are capable of altering the cell’s function.
Because of their role in cell-cell communication, exosomes are
Improving diagnosis and management of keratoconus attractive therapeutic candidates.After all, exosomes are already capable
of delivering functional biological cargo to cells – a task that has
Keratoconus and related eye diseases are a major cause of vision loss in proven quite challenging to achieve using synthetic systems.
young adults, the primary concern during refractive surgery screening
to treat nearsightedness, and the leading indication for corneal More pertinent to the treatment of non-healing wounds is the role
transplants in the United States. Keratoconus causes the cornea – that exosomes can play in mediating a process known as angiogenesis,
which is normally round – to thin and begin to bulge into a cone-like through which the body creates new blood vessels from preexisting
shape.This cone shape deflects light as it enters the eye on its way to vessels.Angiogenesis is vital to tissue formation and wound healing; a
the light-sensitive retina, causing distorted vision. healthy body controls this process using several “on” and “off ” switches
that either stimulate or inhibit blood vessel formation.
While it is critical to identify corneal ectasia [weakening of the
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Emerging evidence from numerous research groups around the world shows that exosomes play a crucial role in regulating angiogenesis, with
much of the current literature focused on identifying proteins and microRNAs (miRNAs) that contribute to exosome-mediated effects. Jay’s
research group has contributed to this body of work with a recent publication in Scientific Reports, identifying a critical regulatory role for
specific members of a different class of molecules, long non-coding RNAs (lncRNAs).

Unfortunately, exosomes have a number of shortcomings as potential therapeutic vectors, in particular, they have potentially low potency due to
the fact that they contain low amounts of nucleic acid cargo – such as lncRNAs and microRNAs – that are critical to defining their bioactivity.

To overcome this limitation, Jay is working with members of his Biotherapeutic Development and Delivery Laboratory, as well as with Dr.
John Harmon, professor of surgery at the Johns Hopkins University School of Medicine, to develop a novel technique to exert control over
exosomes derived from endothelial cells – cells that line the interior surface of blood vessels.This approach involves conditioning endothelial
cells by exposure to non-toxic concentrations of ethanol, a relatively cheap and readily available chemical compound.This conditioning has the
effect of enhancing the expression of specific lncRNAs that promote angiogenesis while diminishing the levels of certain miRNAs that work
to reduce angiogenesis.Thus, the overall effect yields production of exosomes with significantly enhanced angiogenic potential that Jay and his
team believe could be therapeutically beneficial for wound repair.

Moving forward, Jay and his team will explore how additional exosome production parameters can be integrated with ethanol conditioning to
produce highly potent exosomes for wound repair.

BRIDGING THE GAP BETWEEN MICROELECTRONICS, BIOLOGICAL SYSTEMS

Without a doubt, microelectronics devices – from pacemakers to cell phones – are shaping the course of human health and telecommunications.
Now, researchers at the University of Maryland (UMD) are working to create first-of-kind microelectronic devices that connect with biological
systems in ways that could revolutionize the future of electronic device design and computing systems.

“Devices that freely exchange information between the electronic and biological worlds would represent a completely new societal paradigm,” said
William E. Bentley, UMD Fischell Department of Bioengineering professor, director of UMD’s Robert E. Fischell Institute for Biomedical Devices
and the project’s principal investigator.“It has only been about 60 years since the implantable pacemaker and defibrillator proved what devices
could achieve by electronically stimulating ion currents. Imagine what we could do by transferring all the knowledge contained in our molecular
space, by tapping into and controlling molecules such as glucose, hormones, DNA, proteins, or polysaccharides in addition to ions.”

Bentley, Herbert Rabin Distinguished Chair in Engineering Reza Ghodssi (Department of Electrical and Computer Engineering/Institute for
Systems Research), Professor Gregory Payne (Institute for Bioscience and Biotechnology Research),Assistant Professor Massimiliano Pierobon
(University of Nebraska-Lincoln’s Department of Computer Science and Engineering), Biotechnology Scientist Jessica Terrell (U.S.Army Research
Laboratory), and a team of researchers are working to develop devices capable of facilitating the free exchange of information between the
electronic and biological worlds.

To support these efforts, the National Science Foundation (NSF) recently awarded the group a $1.5 million grant through the Semiconductor
Synthetic Biology for Information Processing and Storage Technologies (SemiSynBio) program. SemiSynBio, a partnership between the NSF and
the Semiconductor Research Corporation (SRC), seeks to lay the groundwork for future information storage systems at the intersection of biology,
physics, chemistry, computer science, materials science and engineering.

Despite recent advancements in microelectronics, there remains a technology gap between microelectronics and the biological world.

Today’s consumers, for example, cannot turn to their smart phones to uncover information about an infection or illness affecting their body, nor can
they use their phones to signal a device to administer an antibiotic or drug. One of the primary reasons for this disconnect between the body and

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everyday technology is that microelectronic devices process information using materials such as silicon, gold, or chemicals, and an energy source that
provides electrons; but, free electrons do not exist in biological systems.As such, scientists encounter a major roadblock in their efforts to bridge the
gap between biological systems and microelectronics.

But, Bentley and his team have found a loophole.

In biological systems, there exists a small class of molecules capable of shuttling electrons.These molecules, known as “redox” molecules, can transport
electrons to any location. But, redox molecules must first undergo a series of chemical reactions – oxidation or reduction reactions – to transport
electrons to the intended target.

By engineering cells with synthetic biology components, the research team has experimentally demonstrated a proof-of-concept device enabling
robust and reliable information exchange between electrical and biological (molecular) domains.

Even more, the research group is now working to develop a novel biological memory device that can be written to and read from via either
biological and/or electronic means. Such a device would function like a thumb drive or SD card, using molecular signals to store key information and
requiring almost no energy. Inside the body, these devices would serve the same purpose – except, instead of merely storing data, they could be used
to control biological behaviors.

“For years, microelectronic circuits have had limited capacities in maximizing their computing and storage capabilities, mainly due to the physical
constraints that the building-block inorganic materials – such as silicon – imposed upon them,” Ghodssi said.“By exploring and utilizing the world of
biology through an integrated and robust interface technology with the semiconductor processing, we expect to address those limitations by allowing
our researchers and students to design and develop first-of-kind innovative and powerful bioelectronic devices and systems.”

The research team will work to integrate subsystems and create biohybrid circuits to develop an electronically controlled device for the body that
interprets molecular information, computes desired outcomes, and electronically actuates cells to signal and control biological populations.The
group’s hope is that such a system could seek out and destroy a bacterial pathogen by recognizing its secreted signaling molecules and synthesizing a
pathogen-specific toxin. In this way, the group will, for the first time, explore electronic control of complex biological behaviors.

SemiSynBio builds upon a long history of NSF support for basic research in synthetic biology.This year’s awards address a range of potential
applications, including storing data by using DNA, automating the design of genetic circuits, creating bioelectronics and exploring methods for
molecular communication. Bentley’s group is one of eight new SemiSynBio projects to receive awards this year.

SCHIZOPHRENIA DRUG MONITORING DEVICE RESEARCH
FEATURED ON IEEE SENSORS LETTERS COVER

Research to build schizophrenia drug monitoring lab-on-a-chip devices by Fischell Department of
Bioengineering alumnus Thomas Winkler (Ph.D.‘17) and six colleagues was featured on the cover of
the March 2018 issue of the IEEE Sensors Letters. The paper is a culmination of a four-year collaboration
among researchers from the University of Maryland A. James Clark School of Engineering, the Institute for
Bioscience and Biotechnology Research (IBBR), and the Maryland Psychiatric Research Center (MPRC) at
the University of Maryland School of Medicine.

“The Role of Microsystems Integration Towards Point-of-Care Clozapine Treatment Monitoring in
Schizophrenia” present the first lab-on-a-chip device capable of label- and reagent-free concurrent sensing of
cellular and molecular markers.

The study is specifically geared toward schizophrenia treatment, where concurrent blood monitoring of the
antipsychotic clozapine and white blood cells could lead to improved treatment outcomes.

The researchers approach the challenge from a systems level, considering sensor integration both in parallel and
in series.They evaluate the critical system components for plasma skimming (parallel) and in-blood clozapine
detection (series).They find that plasma skimming is infeasible but, for the first time, demonstrate direct
detection of clozapine in whole blood.With a corresponding series-integrated microsystem, they demonstrate
downstream white blood cell analysis on the same samples using impedance cytometry.

The work was supported in part by the National Institutes of Health, the Robert W. Deutsch Foundation, and the Maryland NanoCenter.

This research builds on ongoing efforts to develop a tool to detect biological signatures in blood that measure the level of
oxidative stress for applications in schizophrenia diagnosis. Read more online at go.umd.edu/oxidativestress

STROKA NAMED OUTSTANDING YOUNG SCIENTIST BY
MARYLAND ACADEMY OF SCIENCES

Fischell Department of Bioengineering (BIOE) Assistant Professor Kimberly Stroka, an alumna of the department (Ph.D.
’11), was named a winner of the 2017 Outstanding Young Scientist (OYS) award by the Maryland Academy of Sciences
and the Maryland Science Center. Stroka was one of four honorees who were recognized for their contributions to
science and engineering at a ceremony hosted by the Maryland Science Center.

“The accomplishments of our 2017 honorees are impressive,” said Mark Potter, president and CEO of the Maryland
Science Center.“[The] four professionals are great examples of why Maryland is a hub of discovery and exploration,
and they are great role models for today’s STEM students.”

Stroka was recognized for discovering a new fundamental mechanism for tumor cell migration by combining
experimental techniques and theoretical modeling. Her efforts include using aquaporins – water channels that
allow water flux across the cell membrane – as possible druggable targets for tumor cell metastasis.

Most recently, Stroka and members of her Cell and Microenvironment Engineering Lab discovered a
connection between biochemical cues from cells in the brain environment and breast tumor cell migration.
Their findings, published in “Astrocytes from the brain microenvironment alter migration and morphology of
metastatic breast cancer cells” in the FASEB Journal, point to key factors that cause breast cancer to metastasize
to the brain.

DR. KIMBERLY STROKA “There is still so little researchers know about how and why tumor cells cross what is known as the blood-
brain barrier to enter the brain environment, commonly referred to as brain tissue,” Stroka said.

The blood-brain barrier is a semi-permeable barrier made up of brain endothelial cells that line the blood vessels in the brain.This barrier plays
a critical role in protecting the brain from foreign substances in the blood, while allowing essential nutrients to reach the brain. Unfortunately,
the BBB is so effective that it also hinders the delivery of potentially life-saving therapeutics to the brain.

To understand why breast tumor cells can overcome this barrier – while many targeted treatments cannot – Stroka and her team of researchers
looked to study astrocytes, one of the most abundant cell types found in the brain.Astrocytes play a key role in supporting the BBB and brain
homeostasis, but recent research indicates that they are also linked to brain metastasis and tumor cell survival across the BBB.

In fact, Stroka and her team have found that biochemical cues from astrocytes actually increase the speed of breast tumor cell migration by
changing their shape. Even more, the research group discovered that when they applied the same biochemical cues directly to the extracellular
matrix – the collection of proteins and carbohydrates that surrounds the cells – there was an even greater increase in tumor cell velocity.

FISHER NAMED TISSUE ENGINEERING CO-EDITOR-IN-CHIEF

University of Maryland Fischell Family Distinguished Professor and Fischell Department of Bioengineering (BIOE) Chair
John Fisher was named co-Editor-in-Chief of Tissue Engineering Parts A, B, and C, effective January 1.

Tissue Engineering is the preeminent biomedical journal advancing the field with cutting-edge research and applications on
all aspects of tissue growth and regeneration.The multidisciplinary journal brings together the principles of engineering and
life sciences in tissue development and regenerative medicine. Tissue Engineering is divided into three parts, providing a central
forum for groundbreaking scientific research and developments of clinical applications from leading experts in the field
that will enable contributions to the ultimate care of patients. Fisher serves alongside co-Editor-in-Chief Dr.Antonios
Mikos of Rice University’s Department of Bioengineering.

Fisher’s work focuses most specifically on Tissue Engineering, Part A, the authoritative peer-reviewed journal
centered on the convergence of the life sciences, engineering, and medicine for the generation of viable
biological tissues to better fundamentally understand and treat human disease. Part A publishes 24 issues per year.

In December 2017, Fisher was awarded the Tissue Engineering and Regenerative Medicine – Americas
(TERMIS-AM) Senior Scientist award for his contributions to the field.

In addition to his role as BIOE chair, Fisher serves as director of the newly established National Institutes of DR. JOHN FISHER

Health-funded Biomedical Technology Resource Center (BTRC) – the Center for Engineering Complex

Tissues – which is dedicated to advancing techniques to create complex tissues and parts of the body, such as for organs and bone.

POSTDOC RECOGNIZED FOR EARLY
COLON CANCER DETECTION RESEARCH

Fischell Department of Bioengineering postdoctoral research associate those of the gastrointestinal (GI) tract.
Qinggong Tang was recently named the recipient of a two-year, Today, white-light endoscopy-guided
$100,000 grant from the Prevent Cancer Foundation to develop an excisional biopsy and histopathology
endoscopic multi-modality optical imaging system for early colon remain the gold standard for GI cancer
cancer detection. diagnosis. Unfortunately, this standard
suffers from high false negative rates
Colorectal cancer is the third most common form of cancer diagnosed due to sampling errors, in large part
in both men and women in the United States, and the second- and because current endoscopy technology
third-leading cause of cancer-related deaths for men and women, cannot detect early-stage subsurface
respectively.When colorectal cancer is found at an early stage before lesions.
it has spread, it has a five-year survival rate of 90 percent. But, the
survival rate drops to less than 10 percent once the cancer metastasizes. To tackle this challenge,Tang, Chen, DR. QINGGONG TANG
Unfortunately, only 25 percent of colorectal cancer cases are discovered
in the early stage. and fellow lab members are working

Recognizing this,Tang is working with fellow members of BIOE to develop a new generation of endoscopic imaging technology by
Associate Professor Yu Chen’s Biophotonic Imaging Laboratory
to develop new diagnostic tools – including novel high-resolution combing two complementary optical imaging modalities: fluorescence
imaging techniques – that could aid early colorectal cancer detection,
and guide biopsy procedures to improve sampling accuracy. laminar optical tomography (FLOT) and optical coherence

When followed by preventative therapy, the new tools could lead to tomography (OCT).Their hope is that FLOT would provide depth-
significant improvement in patient survival and quality of life.
Like colorectal cancer, many cancers arise from epithelial layers such as resolved quantitative molecular information using molecular-specific

contrast agents, and OCT would provide high-resolution (micron-

level) morphological images. Put simply, the team believes that by

combining these two techniques, they can create a multi-modal

imaging technology capable of producing high-sensitivity and high-

specificity imaging for early detection of colorectal cancer as well as

other GI and epithelial cancers.

ANJANA JEYARAM NAMED PHRMA FOUNDATION PREDOCTORAL FELLOW

The Pharmaceutical Research and Manufacturers of America therapeutic cargo into EVs.
(PhRMA) Foundation awarded Fischell Department of
Bioengineering Ph.D. student Anjana Jeyaram a two-year, “Current exogenous loading methods
$20,000-per-year predoctoral fellowship in pharmaceutics. are inefficient and may damage
EV cargo, limiting therapeutic
Jeyaram, a member of BIOE Assistant Professor Steven Jay’s effectiveness,” Jeyaram said.
Biotherapeutic Development and Delivery Lab, was recognized for
her extensive research on engineering extracellular vesicles (EVs) to Recognizing this, Jeyaram envisioned
enhance therapeutic efficacy and clinical translatability. She recently
published a review article outlining key considerations in her work in a way to improve the therapeutic
AAPS Journal in a piece titled,“Preservation and Storage Stability of
Extracellular Vesicles for Therapeutic Applications.” efficacy of EVs. By delivering vesicles

EVs are ubiquitous, biologically-generated nanovesicles that are with controllably increased levels of ANJANA JEYARAM
released by cells and have the ability to naturally transfer nucleic specific miRNAs within a biomaterial
acids. Because of their role in intercellular communication, EVs have
emerged as potential therapeutic delivery vehicles. EVs may have the vehicle, Jeyaram proposes a way to
ability to cross biological barriers that often inhibit drug delivery,
such as the blood-brain barrier. But, researchers face a number of promote sustained retention at the target site. Moving forward, she
challenges when it comes to storing EVs for clinical use and loading
aims to enhance EV bioactivity through active loading of miRNAs,

and optimize extracellular storage protocols to enhance long-term

cargo retention and bioactivity.Additionally, Jeyaram is working

to increase EV retention time in the target area while enhancing

therapeutic outcomes using an injectable hydrogel-mediated delivery.

THE GRADUATE PROGRAM In addition to the Ph.D., Fischell Department of Bioengineering
program degree options include a Master of Engineering (M.Eng.)
80 graduate students currently enrolled degree, Graduate Certificate in Bioengineering, Doctor of Medicine/
3.61 average GPA for admitted students Master of Science (M.D./M.S.), and a Doctor of Medicine/Doctor of
161 average GRE Q Philosophy (M.D./Ph.D.).
40% newly enrolled were women
For more information:
www.bioe.umd.edu/graduate

SCARCELLI HELPS DEVELOP TECHNOLOGY TO DELIVER IMAGES OF
BIRTH DEFECT AS IT HAPPENS

In the first few weeks of pregnancy and often before a woman even Brillouin spectroscopy is a
realizes she’s pregnant, an embryo will have already developed a neural light scattering technology
tube, a hollow structure made of cells that will eventually become that will sense tissue
the brain and spinal cord. Now, with $3.2 million from the National mechanical properties,
Institutes of Health, Giuliano Scarcelli—an assistant professor in which growing evidence
the Fischell Department of Bioengineering—is part of an effort to has suggested is critical to
tackle the evolutionary anomaly of why the neural tube closes in most the neural tube’s success
embryos but remains open in others, leading to birth defects such as in closing. Scarcelli has
spina bifida and anencephaly. invented and led the
development of Brillouin
Neural tube defects are the second most common structural microscopy over the past
birth defect in humans, affecting upwards of 500,000 pregnancies 10 years.
worldwide and approximately 2,400 pregnancies each year in the
United States. Embryonic development involves the interplay of “Generally, to characterize
driving forces that shape the tissue and the mechanical resistance the stiffness of a material,
that the tissue offers in response. However, tissue biomechanics is not you need to stretch and
well understood because of the lack of techniques that can quantify pull that material—which
the stiffness of tissue in high resolution and without manipulating or usually destroys it.This
damaging the tissue. new Brillouin technology enables us to determine the mechanical
properties of embryonic tissue in a noninvasive way and as that tissue
Led by Professor Kirill Larin of the University of Houston and grows,” says Scarcelli.
together with Professor Richard Finnell of the Baylor College of
Medicine, the research team including Scarcelli will create new The work fills a significant data gap in understanding neural tube
technology combining Brillouin spectroscopy and optical coherence closure biomechanics.The research team says it could have a
tomography (OCT) to deliver 3D images of the mechanical factors dramatically positive impact on our understanding of neural tube
at play when the neural tube closes and—in so many cases—when it defects and drive novel treatments for at-risk embryos.
does not.
“It’s still one of the great mysteries of life—no one on Earth knows
Most commonly used to examine the retina, OCT is an imaging how this happens, and that is really exciting to us,” says Larin,“because
technology that uses light waves to take cross-section pictures. we will be the ones to find out.”

RESEARCHERS INVESTIGATE HOW TO PROTECT AN
EMERGING BIOFUEL CROP FROM DISEASE

Fischell Department of Bioengineering Associate Professor Edward development of transgenic poplars as a tool for the research
Eisenstein is part of a collaborative, multidisciplinary research project community to accelerate the evaluation of disease models.
awarded a $1.1M U.S. Department of Energy (DOE) grant to
elucidate the mechanism of rust pathogenesis in poplar trees in The limited understanding of how rust pathogens subvert host
an effort to engineer durable resistance for this important, second immunity to cause disease in poplar has constrained efforts to widely
generation biofuel crop. adopt poplar as a useful bioenergy feedstock. Recent developments in
bio-renewable energies including growth of poplar tree farms, more
The aim of the three-year project is to investigate the molecular basis efficient extraction of bioenergy on a commercial scale, and year-
for the virulence of leaf rust and other diseases toward Populus species round harvesting, have renewed interest in this woody crop. Poplars
in order to address the challenge of engineering resistance against the are more desirable for biofuels than many other crops because of their
pathogens. Genome-wide, high-throughput screens will be used to (i) rapid growth, ability to quickly produce a significant amount of plant
elucidate the mechanisms by which the rust pathogen, Melampsora biomass, and because they have high cellulose and low lignin contents.
larici-populina, suppresses host immunity, (ii) identify the host factors The high cellulose content provides the carbohydrates necessary
that are prime targets, and (iii) pinpoint the nutrient pathways that to produce bioenergy and the low lignin content makes it easier to
extract carbohydrates from the biomass for conversion into liquid
are hijacked by the pathogen to spread disease. This transportation fuels.
information will shed new light on rust-poplar
interactions and enable “Our unique team brings together the expertise needed to understand
the cellular and molecular mechanisms that rust pathogens deploy
to overtake the poplar immune system, which is precisely the

information we need to construct genetically engineered poplar
variants that would be more useful as a
biofuel feedstock,” said Eisenstein.

FISCHELL DEPARTMENT OF BIOENGINEERING LAUNCHES REU PROGRAM

This summer, the University of Maryland (UMD) Fischell Department the things you’re learning are new, and the types of researchers you’re
of Bioengineering (BIOE), with support from the National working with offer
Science Foundation (NSF), kicked off a new initiative to introduce new perspectives,”
undergraduates from institutions across the country to new approaches said Ekta Patel,
to engineering cells, tissues, and organs. a rising senior
studying biomedical
BIOE’s summer NSF Research Experience for Undergraduates (REU) engineering on
enlists undergraduates to investigate new engineering technologies a pre-medicine
for constructing and mimicking tissues and organs. In its inaugural track at Arizona
year, the 10-week BIOE REU team welcomed 10 students from State University.
bioengineering, mechanical engineering, pre-med, and materials Patel spent this
science and engineering programs across the country. summer working
in the UMD
This year’s students supported projects in cancer cell microenvironment Tissue Engineering
and migration on a chip, 3D printing and microsystems for extracellular and Biomaterials
vesicle biomanufacturing, and 3D-printed scaffolds for improved tissue Laboratory, for which
regeneration. Each research project is conducted as a collaboration BIOE Professor and
between UMD and the U.S. Food and Drug Administration, making Chair John Fisher is principal investigator.
the BIOE REU unlike any other available in the country.At the end
of the BIOE REU program, students take part in the FDA’s annual “I previously conducted a lot of research dealing with sensory systems
research fair, where they present their work to other undergraduate and circuitry, so I had never worked in a wet lab before,” she said.
researchers as well as FDA technical staff, non-FDA scientists, and even “Getting to the University of Maryland and being able to work in
the FDA Commissioner. tissue engineering was so different.The REU program is very nicely
designed and it offers an opportunity to immerse yourself in something
“REU programs in general offer a great opportunity for students to go that you might not have otherwise explored.”
to a completely different university, where the facilities are different,

UMD TO LEAD MILESTONE NSF HIGH SCHOOL ENGINEERING PILOT COURSE

With a nearly $4 million grant from the National Science Foundation will refine a curriculum developed by the American Society for
(NSF), the University of Maryland will lead a first-of-its-kind Engineering Education (ASEE) and the College Board.The curriculum
nationwide pre-college course on engineering principles and design. will integrate engineering principles and a student design project,
The pilot program, entitled Engineering For US All (E4USA), will and it will align to the Next Generation Science Standards for K–12
test the effectiveness of a standardized educational curriculum across education, developed by 26 states and other partners.
multiple states.The course is intended to lead to an eventual pathway
for high school students to earn college credit. Vanderbilt University will evaluate the curriculum, student learning,
and teacher training.Additional collaborators include NASA Goddard,
“Every student should have access to a high-quality pre-college Project Lead the Way, and the College Board. Over 1,000 students at
curriculum that teaches engineering principles and practices while approximately 40 high schools are expected to complete the pilot over
incorporating design-based experiences,” said Darryll J. Pines, principal the three-year period.
investigator (PI) and dean of the University of Maryland’s A. James
Clark School of Engineering.“The skills learned in engineering “E4USA provides guidelines for learning management systems and the
classrooms enable students from demographically and geographically online analytical tools for centralized data collection and protocols,”
diverse schools to not only become better prepared for the academic said Leigh Abts, co-PI and associate researcher with a joint appointment
challenges within science, technology, engineering, and math (STEM) in the Fischell Department of Bioengineering and UMD’s College
courses, but to become better prepared for life.” of Education. “E4USA will offer teachers online, mentored, video-
based professional development supported by online modules and
The project is in partnership with Arizona State University, Morgan mentoring.”
State University, and Virginia Tech. During the pilot, researchers

THE UNDERGRADUATE PROGRAM The undergraduate program of the Fischell Department of Bioengineering is
founded in biology,driven by human health issues,and emphasizes innovation.
453 students enrolled in 2017-18 Our objective is to merge the principles and applications embedded in
4.44 average GPA for admitted students engineering with the sciences of biology, medicine, and health.
731 average SAT Math for admitted students
55.2% newly enrolled were women For more information:
www.bioe.umd.edu/undergraduate

DUNCAN EARNS POWE AWARD FOR EARLY CAREER RESEARCH

Fischell Department of Bioengineering Assistant Professor Gregg Duncan was recently awarded the prestigious Ralph E.
Powe Junior Faculty Enhancement Award by Oak Ridge Associated Universities (ORAU). Duncan was recognized for
his efforts to optimize viral gene therapies that could one day be used to treat a variety of diseases such as Huntington’s
disease, retinal dystrophy, and cancer.

In gene therapy, bioengineers use what are known as viral vectors to deliver genetic material into cells. Recently, gene
therapy using adeno-associated virus (AAV) vectors has emerged as a leading viral gene delivery system because of
AAV’s ability to infect many types of cells and tissues.Additionally,AAV has a strong safety profile compared to
other clinically tested viruses.

DR. GREGG DUNCAN “With the growing usage of AAV for gene therapy, it is important to understand how AAV – once
administered – distributes through the body, as this will impact its effectiveness and long-term safety,” Duncan
said.

With this in mind, Duncan and members of his Nanoscale Interfacial Biology and Engineering Laboratory
are working to develop a hybrid AAV nanoparticle system for imaging in vivo with high contrast, near infrared-emitting nanoparticles placed
inside the virus core.This will allow for direct assessment of AAV biodistribution in vivo, offering a novel tool in the evaluation and testing of
AAV-based gene therapy approaches.

JEWELL NAMED AICHE 2018 NSEF YOUNG INVESTIGATOR, OWENS CORNING RECIPIENT

Fischell Department of Bioengineering (BIOE) Associate Professor and Associate Chair Christopher Jewell was named
the recipient of two national awards by the American Institute of Chemical Engineers’ (AIChE) in recognition of his
work in engineering and immunology.The AIChE Nanoscale Science & Engineering Forum (NSEF) selected Jewell
for the 2018 Young Investigator award, while the AIChE Materials Engineering and Sciences Division (MESD)
awarded Jewell the Owens Corning Early Career Award.

The NSEF Young Investigator Award recognizes one individual each year for outstanding scholarship,
commercialization, education, or service in nanoscience and nanotechnology by engineers or scientists in the
early stages of their professional careers.The Owens Corning Early Career Award recognizes outstanding
independent contributions to the scientific, technological, educational or service areas of materials
science and engineering for a faculty member under the age of 40.

Prior to the most recent AIChE awards, Jewell, a Robert E. Fischell Institute for Biomedical Devices DR. CHRISTOPHER JEWELL
faculty member, was named a Damon Runyon-Rachleff Innovator and a National Science Foundation
(NSF) CAREER Award recipient. He has authored more than 75 manuscripts and patents, including
papers in ACS Nano, Cell Reports, Nature Materials, Proceedings of the National Academy of Sciences, and
Nature.

JAY RECEIVES NATIONAL SCIENCE FOUNDATION CAREER AWARD

Fischell Department of Bioengineering (BIOE) Assistant Professor Steven Jay was selected for a five-year, $522,000 National
Science Foundation (NSF) Faculty Early Career Development (CAREER) award. Jay was recognized for his efforts to develop
a new class of biotherapeutics using cell-derived structures known as exosomes.

Exosomes are a type of small extracellular vesicle – ubiquitous, biologically-generated structures that naturally transfer nucleic
acids between cells. Decades ago, researchers believed that exosomes did little more than offload cellular waste.Today,
however, exosomes are better understood as “messengers” that carry out a range of important cellular functions such
as the transfer of DNA, RNA, and proteins to other cells, where they are capable of altering the cell’s function.

Increasingly, research has shown that exosomes are vital components of what is known as the paracrine secretome

of numerous cell types, meaning that these vesicles are key mediators of the effects that one cell has on other

cells. In particular, there has been significant interest in exosomes from mesenchymal stem cells (MSC) – adult

DR. STEVEN JAY stem cells that originate from many tissues in the body, including bone marrow, the liver, and the spleen. MSCs
are unique in that they have the capacity to produce several types of skeletal tissue cells such as cartilage, bone,

and fat; as such, they have garnered significant attention for their potential role in regenerative medicine, as

have exosomes from these cells. MSC exosomes have already been shown to be potentially useful for a wide variety of applications, including

therapeutic vascularization, drug delivery to tumors, and many others.

FISCHELL DEPARTMENT OF BIOENGINEERING ANNOUNCES TWO NEW FACULTY

The Fischell Department of Bioengineering and the A. James Clark Clyne received her bachelor’s degree in mechanical engineering from
School of Engineering are honored to welcome two new faculty Stanford University and later worked as an engineer in the GE Aircraft
members,Associate Professor Alisa Morss Clyne and Assistant Professor Engines Technical Leadership Program for four years, concurrently
Katharina Maisel. Both Clyne and Maisel will begin their appointments earning her master’s degree in mechanical engineering from the
in January 2019. University of Cincinnati. She received her doctorate in medical and
mechanical engineering from the Harvard-MIT Division of Health
Clyne is an expert in endothelial cell biology, biomechanics, and Sciences and Technology.

metabolomics. Leading up to her BIOE appointment, Clyne served

as an associate professor of mechanical engineering, with a courtesy Maisel is an expert on mucosal drug delivery, lymphatic endothelial

appointment in the School of Biomedical cell biology, and immunoengineering. Her

Engineering, Science, and Health Systems, at research interests include designing tools

Drexel University.There, Clyne also served as for investigating roles of stromal tissues – in

director of the Vascular Kinetics Laboratory, particular, the lymphatics – in disease pathology;

which investigates integrated mechanical and and developing novel immunomodulatory

biochemical interactions among cells and drug and drug delivery targets for improved

proteins of the cardiovascular system. She is treatment of mucosal diseases including, but not

particularly interested in how endothelial cell limited to, allergies, lymphangioleiomyomatosis

mechanotransduction changes in a diseased (LAM), and inflammatory bowel disease. Her

environment, and how fluid shear stress and doctoral research focused on the development of

substrate mechanics affect biochemical binding DR. ALISA MORSS DR. KATHARINA nanocarriers and fluid-absorption-inducing drug
kinetics, transport, and signaling. CLYNE MAISEL delivery vehicles for improving gastrointestinal
drug delivery. For her postdoctoral research,

Clyne received the National Science Foundation (NSF) CAREER Maisel studied the immunomodulatory roles of
award in 2008, an American Heart Association (AHA) National
Scientist Development Grant in 2010, and the Biomedical Engineering lymphatics in allergic airway inflammation and the immune response
Society-Cellular and Molecular Bioengineering (BMES-CMBE)
Rising Star award in 2011. She has received research and educational lymphangioleiomyomatosis, a rare lung disease, to develop new
funding from NSF, the National Institutes of Health (NIH),AHA, the
U.S. Department of Education, the Nanotechnology Institute, and molecular targets for treatment.
the State of Pennsylvania, and she has published in diverse journals
including Lab on a Chip, the Journal of Biomechanics, Annals of Biomedical Maisel earned a bachelor’s degree in materials science and engineering
Engineering, and Tissue Engineering. She is a fellow of the American from the University of Michigan, and a Ph.D. in biomedical engineering
Society of Mechanical Engineers (ASME) and the AHA, and a member from Johns Hopkins University.As a graduate researcher, she received
of the American Society for Engineering Education (ASEE), BMES, an NSF graduate research fellowship, and the JHU Center for
the North American Vascular Biology Organization (NAVBO), and Nanomedicine Award for Research Excellence.As a postdoc, Maisel
the Society of Women Engineers (SWE). Her teaching focuses on cell began as a T32 fellow in respiratory biology and then was awarded
and matrix biomechanics, with a particular focus on cardiovascular an F32 NIH NRSA postdoctoral fellowship. Maisel’s work has been
fluid mechanics, and she founded several programs to enhance diversity published in various journals including the Journal of Controlled Release,
within engineering. Advanced Drug Delivery Reviews, and the Journal of American Respiratory
and Cellular Biology. Maisel has also continuously supported enhancing
retention of women in STEM, and, as part of this effort, co-founded
the Graduate Women’s Empowerment Network (GWEN) at Johns
Hopkins University.

BIOENGINEERING CELEBRATES
OPENING OF A. JAMES CLARK HALL

The Fischell Department of Bioengineering and the Robert E.
Fischell Institute for Biomedical Devices formally moved into the
new A. James Clark Hall in Spring 2018. The 184,000-square-
foot facility fosters transformative engineering and biomedical
technologies to advance human health. It serves as the flagship
of University of Maryland bioengineering and a hub for new
partnerships and collaborations throughout the capital region.
Clark Hall has added 38,000 square feet of new department
space for bioengineering, and features 39,666 square feet of
lab space, including three bioimaging labs, a state-of-the-art
computational lab and the 240-seat Leidos Innovation Lab.

»LEARN MORE BY VISITING GO.UMD.EDU/CLARKHALL

4102 A. James Clark Hall
8278 Paint Branch Dr.
University of Maryland
College Park, MD 20742

The Fischell Department of Bioengineering at the University of Maryland
is the home of an emerging academic discipline, exciting interdisciplinary
degree programs, and faculty and students who want to make a difference
in human healthcare through education, research and invention.

For more information about the department, please visit:
www.bioe.umd.edu

Follow us on Twitter and Instagram: @UMDBIOE

FISCHELL DEPARTMENT OF BIOENGINEERING BY THE NUMBERS:

$14.1M in Research Expenditures in 2017-18 22 State-of-the-art Laboratories
184,000 Square-Foot Building Opened in 2018 24 Senior Capstone Projects in Spring 2018
38,000 Square Feet of New Department 3 NIH R01 Award Recipients in 2018

Space with Opening of A. James Clark Hall (Dr. Steven Jay, Dr. Christopher Jewell, and
Dr. Giuliano Scarcelli)
30 Invention Disclosures Filed in 2017-18
22 Tenure/Tenure-Track Faculty 1 AIMBE College of Fellows inductee in 2018

(Dr. Xiaoming He)