2017 Nano-Bio Report

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Table of Contents translation

education 4 From Graduate Student to Recognized Cancer Fighter

22 Hai-Quan Mao Featured as Tech Entrepreneur

8 Several INBT Students Announced as Siebel Scholars

23 NexImmune Receives $23 Million for AML Trials

outreach

24 Masters Co-Op Unlocks True Engineering Careers

10 National Nanotechnology Day

by the numbers

12 Highlights of the 11th Annual Nano-Bio Symposium

26 Awards

14 Virginia Tech Tours INBT

27 Education/Training

research 16 Core Research Areas: New Directions in Nanoscience 18 New Insights on the Role of Bioelectricity on Cell Migration and Metastatic Disease 19 Serendipity Leads to Simpler Method for Analyzing DNA 20 Combating Heart Disease with Stem Cells

Johns Hopkins Nano-Bio Report Editor-in-Chief Gina Wadas Art Director Martin Rietveld Graphic Designer Maureen Punte Photographers and Illustrators Michael Ciesielski, Cara Conley, Allan Doyle, Jon French, Martin Rietveld, Sarvenaz Sarabipour, Gina Wadas

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We encourage your comments and feedback. Send correspondence to: Johns Hopkins University Institute for NanoBioTechnology Suite 100, Croft Hall 3400 North Charles Street Baltimore, MD 21218 inbt@jhu.edu 410-516-5634 inbt.jhu.edu Follow INBT on social media:

Letter from the Directors Welcome to the latest edition of the INBT Nano-Bio Report.

We are delighted to share the exciting developments from 2017, which strengthen our abilities in research, education, translation, and outreach.

INBT’s central mission brings scientists, physicians, and en-

gineers across disciplines together in a collaborative effort to solve global challenges in healthcare and the environment.This past year, we continued to consolidate our core research areas.

In addition, we made improvements to our annual symposia.

Engineering Vascularization (2017) and Advanced Biomanufacturing (2018) are evidence that we have become more adept at facilitating integration and collaboration among disciplines.

Translating our research and technologies from laboratory to marketplace has also been successful. We celebrate the accomplishments of our faculty and students who work collaboratively with industry, and we encourage and support them to pursue their own entrepreneurial goals.

We are incredibly pleased to showcase the growth of our Masters Co-Op Program. Companies across the Mid-Atlantic are expressing interest in this unique and mutually beneficial program. In addition, students are interested in the exceptional educational experience the program offers.

The INBT team is poised for an exciting future of scientific discovery.We hope you join and engage with us in our pursuits.

Sharon Gerecht Director

Hai-Quan Mao Associate Director

“ we continued to consolidate our core research areas” Engineering for Cancer Therapies Unraveling the life of both normal and cancerous cells at a precise level of detail, through INBT’s Physical SciencesOncology Center.

Stem Cells and Regenerative Engineering Harnessing the power of stem cells to repair and regenerate damaged tissues due to injury or disease.

Diagnostic Tools Engineered for Early Detection Integrating technologies and tools to diagnose and treat disease earlier and quicker with higher levels of accuracy and specificity.

Learn about our research on page 16.

From Graduate Student to Recognized Cancer Fighter For a young scientist, Hasini Jayatilaka has reached the kind of success that takes many researchers an entire career to achieve. During her training at the Institute for NanoBioTechnology (INBT), she discovered mechanisms that cause cancer cells to separate from tumors and spread throughout the body, a process known as metastasis. She also discovered a cocktail of drugs that slows, and in some cases, stops metastasis.

These discoveries have received international recognition and attracted the attention of many media outlets, organizations, professionals, and audiences.

Story sponsored by the Physical Sciences-Oncology Center

4  education

Jayatilaka completed her bachelor’s degree in 2013 and her PhD in 2017, both in chemical and biomolecular engineering at Johns Hopkins University. During her sophomore year, she found herself performing the early stages of her famed work under the mentorship of Denis Wirtz, co-founder and core faculty member of INBT, Johns Hopkins University Vice Provost for Research, and Theophilus Halley Smoot Professor of Engineering Science.

Her research culminated in a May 2017 article that has become one of the top-read pieces in Nature Communications’ history. It sparked widespread interest and garnered coverage

research. That really inspired me to take risks and test my theories, which turned out to be correct,” said Jayatilaka.

in more than 70 media outlets. Not long after, she was nominated for the 2018 Forbes’ “30 Under 30” list, and spoke about her re-

“ From the moment I entered his lab, Dr. Wirtz encouraged me to think deeply about the field and the observations “From the moment I entered his lab, Dr.Wirtz I witnessed in encouraged me to think deeply about the field and the observations I witnessed in my my research.”

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search at TEDxMidAtlantic’s “Superpowers” themed event. Jayatilaka will also be featured in HERstories, a short form series from Lifetime that profiles women who are breaking boundaries, defying stereotypes, and making a difference in their communities.

Now, Jayatilaka conducts research in the laboratory of Kara Davis at Stanford University School of Medicine’s Department of Pediatrics in the Division of Hematology and Oncology. She is working to develop better immunotherapies for pediatric cancers such

as neuroblastoma. While her research has received widespread media attention, her focus is unchanged.

Her hashtag, #hasinieffect, which began as a way of keeping track of the activities with her team of undergraduate students, has now become a recognized symbol of her research. “I love my work on developing new methods to target this terrible disease. While the attention has been great, my interests and goals remain on improving patients’ health,” she says.

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Several INBT Students Announced as Siebel Scholars Siebel scholarships are prestigious awards that honor about 100 of the top graduate students nationwide in business, bioengineering, computer science, and energy science programs. The 2018 recipients include five students from Johns Hopkins University, and four of them are from the Institute for NanoBioTechnology (INBT).

INBT awardees include Daniel Lewis from

Sharon Gerecht’s lab, Alyssa Kosmides from Jonathan Schneck’s lab, Randal Meyer from Jordan Green’s lab, and Sarah Friedrich from Jeff Wang’s lab. The recipients are selected during their final year of studies based on their outstanding academic performance and leadership and will receive a $35,000 award.

Photo caption: Siebel scholar awardees include Boombim Limpitikul (top left), Randal Meyer (top middle), Daniel Lewis (top right), Sarah Friedrich (bottom left), and Alyssa Kosmides (bottom right).

Photo courtesy of Will Kirk, Homewood Photography.

8 education

National Nanotechnology Day

10  outreach

National Nanotechnology Day is intended to raise awareness of nanotechnology, and celebrates not only how it enriches lives, but also the opportunities it holds for the future. Held each year on October 9, the event honors the nanometer scale of 10–9 meters. Attendees of INBT’s event enjoyed nano-themed food, a selfie booth, a raffle prize, socializing with numerous INBT lab members, and practicing their building skills with Nano-blocks.

outreach 11

Highlights of the 11th Annual Nano-Bio Symposium Blood vessels play a dual role in providing healing, as well as spreading diseases throughout the body.

While vascular systems carry vital nutrients, they are also a pathway for malignancies to infiltrate other body systems. Researchers face the challenge of encouraging blood vessel formation in one instance, while inhibiting formation in another.

Such was the theme of “Engineering Vascularization,” the 11th annual Nano-Bio Symposium, jointly organized by INBT and the Physical Sciences-Oncology Center. The event, held May 5, 2017, featured 60 posters from student and post-doctoral fellows from labs across the Johns Hopkins community, and attracted about 125 attendees.

“The yearly symposium is a reminder of the importance of sharing discoveries in research,” says Sharon Gerecht, Director INBT, Kent Gordon Croft Investment Management Faculty Scholar, and professor in the Department of Chemical and Biomolecular Engineering. “Research at the interface of biotechnology and medicine has and continues to make great advances, but the field still has many challenges. That is why we need the collective forces of those in academics, clinics, industry, and government to work together on interdisciplinary challenges. INBT is passionate about these collaborations and advancements and this is why we continue to host this symposium,” she said.

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The 12th Annual Nano-Bio Symposium will be held Friday, May 4, 2018 on the Johns Hopkins Homewood Campus. The theme of the symposium will be Advanced Biomanufacturing.

outreach 13

Virginia Tech Tours INBT INBT hosted 10 undergraduate nanosci-

and exposed students to the direct impact ence students from Virginia Tech’s Division of nanotechnology and bringing new techof Nanoscience, along with their associ- nologies to market. The students toured ate professor of biological sciences, Carla several INBT labs on the Homewood Finkielstein, and academic advisor, Cara campus and at the School of Medicine, atConley, on November 6, 2017. tended INBT’s 3rd Annual Undergraduate Symposium, and listened to lectures by facThe visit highlighted several of INBT’s re- ulty in which they discussed their research search projects and education programs, accomplishments and challenges.

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Core Research Areas:

New Directions in Nanoscience The Johns Hopkins Institute for NanoBioTechnology is an exceptionally diverse, multidisciplinary team of faculty, researchers, and students. This ambitious team uses its collective skills and knowledge, combined with the collaborative research environment, to push the boundaries of nanoscience. Their results produce innovations that address fundamental and complex topics in basic science, engineering, and medicine.

Engineering for Cancer Therapies Most cancer research is viewed from a clinical perspective, whereas INBT researchers use an engineering approach. This method provides a fresh perspective to diagnosing and treating cancer. INBT brings together engineers and clinicians to unravel the mysteries of how cancer cells move, grow, divide, and interact with their surroundings in a threedimensional environment. Such work is also performed in our Physical Sciences-Oncology Center (PS-OC).

Diagnostic Tools for Early Detection Time is an important variable to effectively diagnose and treat diseases.

INBT researchers are developing new technologies to diagnose diseases quickly, accurately, and using minute sample sizes. This technology allows researchers to better understand diseases, pre-screen potential drugs, and help physicians choose the most effective treatments for the best patient outcomes.

Stem Cells and Regenerative Engineering While the body is proficient at tissue repair, sometimes the severity of certain diseases or injuries are beyond the body’s capability to repair.

INBT researchers are innovating approaches to grow and manage stem cells to repair and regenerate various tissue types damaged by injury and disease, such as blood vessels, bone, cartilage, and muscles.

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  research  17

New Insights on the Role of Bioelectricity on Cell Migration and Metastatic Disease The electrical potentials and currents generated within living organisms are known as bioelectricity. Electrical fields in the body direct many biological processes such as embryo development, wound healing, immune responses, and the spread of cancer and other diseases. However, how cells sense and respond to electrical fields is unknown.

Research performed in INBT labs

by Yu-Ja Huang, Peter Searson, and Jordan Green, along with Alfredo Quiñones-Hinojosa of the Mayo Clinic in Jacksonville, Florida, discovered that this process is regulated by charged polymers, called heparin sulfate, on the cell’s membrane. The polymers sense the electrical field and direct the cell to migrate toward the field.

By observing brain cells in a microfluidic device, researchers can study the directional movement of cells using an external electrical field. The research offers significant insights into understanding the mechanism of cell migration and the spread of cancer, and the role of bioelectricity on cell function. It also shows further potential to using external electrical fields as a possible therapeutic in the treatment of cancer and other diseases.

18 research

Serendipity Leads to Simpler Method for Analyzing DNA

A team lead by INBT faculty member Jeff Tza-Huei Wang and PhD student Sarah Friedrich, experienced great excitement when they unintentionally discovered a new method that improves the process of testing DNA. In many fields, such as healthcare, forensics, and homeland security, concentrating DNA is a critical step in preparing samples for further testing in different devices. In standard practices, DNA is concentrated by applying an external electric field because the molecules are highly charged and this easily manipulates them. While the team was working to refine this practice, they observed the DNA spontaneously concentrating without using the electric field.

What the team observed was a phenomenon they call molecular rheotaxis (MRT).

Rheotaxis refers to an organism’s movement toward or away from a fluid current.

“The reason we called it MRT is because it

reminded us of how fish orient their bodies with the water current,” said Friedrich.

The team’s method uses a pressure-driven fluid flow, which creates a secondary force acting in the opposite direction. It is the secondary force that concentrates the DNA. The new method is simple and offers a range of potential applications when testing for diseases or DNA abnormalities. It could reduce the time needed to test samples, improve DNA sensitivity to reduce the possibility of false-negative results, and could be used in conjunction with other DNA testing devices. Furthermore, the method offers new possibilities for designing new devices since electricity is not required.

research 19

Combating Heart Disease with Stem Cells Cardiovascular disease, also called heart disease, are umbrella terms for disorders that effect the heart and blood vessels, and are the number one cause of death worldwide.

Damage to these tissues can have devastating effects on the cardiovascular system (CVS) and other body systems as they depend on the CVS to supply them with vital nutrients. Therefore, restoring damaged heart and blood vessel tissues is a major research focus.

One promising area of study is using hydrogels and stem cells to create 3-D vascular systems in a lab that can later be grafted into a patient’s body to replace damaged tissues.

Hydrogels are a matrix of materials that mimic a natural tissue environment and act as a scaffold for stem cells to grow. However, there are different hydrogel constructions and stem cells used in research.

Hydrogels need to mimic the natural tissue environment and are created using synthetic materials, natural materials, or a mixture

20  research

of both. Stem cells are derived from a variety of sources, including adults and embryos. In a review by PhD student Bria Macklin and INBT Director Sharon Gerecht, they compared the recent cardiovascular advances in stem cells and hydrogels to find the best approaches for engineering the most efficient vascular networks.

Macklin and Gerecht found that a synthetic hydrogel offers more controlled, customized, and predictable blood vessel formation.

They also noted that using a stem cell type called induced human pluripotent stem cells, which are derived from patients, offer opportunities to generate the various cell types needed to grow complete vascular tissues.

When combined, these characteristics allow for a more defined, healthy vasculature system and show potential to further advance personalized cell-based therapies to combat cardiovascular disease. 

Cells communicate using a network of pathways, which includes chemical and physical interactions. Understanding these pathways provide researchers important details about how healthy and unhealthy cells function. However, their complexity makes researching them challenging.

That is where computational modeling can help. When combined with experimental measurements, computational biochemistry models allow researchers to view and study cell signaling networks in a new way. This is an important tool in healthcare to create personalized cell models for patients.

The illustration, by Martin Rietveld and Allan Doyle, shows an artistic impression of cell signaling pathways. Created for INBT postdoc Sarvenaz Sarabipour and the MacGabhann lab and appears in Biochemistry.

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Hai-Quan Mao Featured as Tech Entrepreneur INBT Associate Director Hai-Quan Mao was featured in the winter issue of JHU En-

cells in the surrounding damaged tissue repair or grow new tissue.

gineering Magazine about technology entrepreneurship. With the creation of the Johns Hopkins Technology Ventures, the university has been strongly advocating and supporting Hopkins community members to engage in enterprise to accelerate technology transfer and commercialization.

Founded in 2015 by Mao, Justin Sacks, Sashank Reddy, and Russell Martin, with seed funding from Johns Hopkins Technology Ventures’s FastForward program, LifeSprout LLC specializes in a synthetic regenerative material of biodegradable nanofibers infused in a hydrogel.

The materials mimics the body’s natural tissue microenvironment and acts as a scaffold in wounds or soft tissue space. The scaffold helps

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Mao attributes his success to close collaboration with his market audience. Making sure a product can survive on the market, the product needs to be designed with clear understanding of how it will be used in the clinic. Such a product is more likely to be successful when you can engage surgeons and practitioners to build it from scratch and include critical features from the users’ perspectives.

NexImmune Receives $23 Million for AML Trials What started as an idea built from the basic principles of immunotherapy by Jonathan Schneck, INBT affiliate faculty, and his lab, has turned into NexImmune, an emerging biopharmaceutical company aimed at using precision nanotechnology to activate the body’s own immune system to treat cancer and other diseases.This technology is still being explored in Schneck’s lab by INBT PhD candidates John Hickey and Alyssa Kosmides.

In December 2017, NexImmune received a $23 million investment from ArrowMark Partners, Piedmont Capital Partners, and existing investor Barer & Son Capital Partners to bring the study of acute myelogenous leukemia (AML) and/or myelodysplastic syndromes through phase I/II of clinical trials using adoptive cellular therapy (ACT) techniques originally developed in Schneck’s lab.

“ Personally, there is nothing more rewarding in medicine than to be able to offer new treatment design and potentially help those in need.”

Myelodysplastic syndromes are a group of disorders characterized by the disruption of blood cell production, which includes AML. AML is a

cancer of the blood and bone marrow and has about 20,000 new cases diagnosed every year.

The clinical trial encompasses taking healthy T cells from donors, use the ACT technology to target and activate specific cancer-fighting T cells, and then inject them into AML patients.

Schneck’s research-based work in immunotherapy transformed into clinical manufacturing is an example of the importance of investing in technology-based platforms in medicine. “To see Neximmune close a series A funding and now advance into clinical trials is very exciting. We are starting to see the fruits of our research and development efforts take form and offer new treatment and hope to patients. Personally, there is nothing more rewarding in medicine than to be able to offer new treatment design and potentially help those in need,” said Schneck.

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Masters Co-Op Unlocks True Engineering Careers Training engineering students for a successful career is challenging. Students need a well-balanced curriculum that includes fundamental science and engineering theory, as well as opportunities to apply their knowledge to everyday issues. While learning in classrooms or laboratories teaches technical skills, it is the tangible experience gained through practical work that teaches them what a real engineering career feels like.

to their classroom education, students spend six months at a leading company to obtain industry experience and gain a broad practical, hands-on background in disciplines such as operations, pilot plants, safety and environmental management, or regulatory affairs. Students are supported through this experience by their department advisor, INBT’s Director of Corporate Partnerships, and supervisor at their mentoring company.

For this reason, INBT created the Masters Co-Operative Education Program. In addition

The program began in the fall of 2016 with one student and one company: Andrew Beamsder-

Students need a well-balanced curriculum that includes learning fundamental science and engineering theory, as well as, knowing how to apply their knowledge to resolve everyday issues.

24  translation

fer working at Becton Dickinson (BD), a medical technology company that manufactures medical devices and instruments. “The people and project management was an eye-opening experience. I designed experiments, as well as created and tested solutions to problems. My team treated me as a full contributing member to the project and not just a student,” said Beamsderfer. He now works full-time for BD.

Company participation has also increased to include MedImmune, WR Grace, and Lonza; all leading companies in pharmaceuticals, specialty materials and chemicals, and biotech and pharmaceutical products and services, respectively.

Since then, eight students have finished the program and recruitment is ongoing. Company participation has also increased to include MedImmune, WR Grace, and Lonza: all leading companies in pharmaceuticals, specialty materials and chemicals, and biotech and pharmaceutical products and services, respectively.

The program offers students more than the development of technical skills. It also gives them a chance to build critical skills such as communication and team collaboration. “I worked on a multidisciplinary team with people who understood different aspects of what it takes to develop a product for clinical needs and bring it to market. They were very involved and invested in my professional development and making the most of my experience at the company,” said Shirley Ng, former Masters Co-Op participant at BD.

The program benefits all participants. Students not only get to experience the thrill of applying their education in a real-world laboratory, but also build their resumes. The participating The program is still in the pilot phase and open to Chemical and Biomolecular Engi- companies not only receive support with a neering and Materials Science and Engineer- project they may not be able to staff, but also ing students. The next phase is to broaden the gain a recruiting advantage for new graduates. interest of other engineering departments and Finally, INBT and Hopkins not only estabbring new corporate partners into the program. lishes a unique engineering program, but also Companies that have expressed interest in par- benefits from a closer collaborative relationticipating include Paragon Bioservices, Air Liq- ship with local industry. uide, and Hopkins Applied Physics Lab (APL).

C-Care will begin hosting students in 2018.

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By The Numbers Proposals Submitted FY17

federal non-federal 43 awards 15 awards

$51.5 Million

$2.9 Million

New & Competing Award Received FY17

federal non-federal 10 awards 6 awards

$1.9 Million

$2.9 Million

10%

20%

37.5%

of all collected awards at the Whiting School of Engineering (FY17) were received by INBT

of all awarded dollars to the Whiting School of Engineering (FY17) were received by INBT

success rate of proposals submitted in FY17

26  by the numbers

Education/Training Research Experience for Undergraduate Applications Received 1,000

950

900

850

800

750

2015

2016

2017

2017 Trainee Classification 15%

6%

205

total trainees

47% Undergraduates

32%

Graduates Post-docs REU students (NSF-funded)

  by the numbers  27

Institute for NanoBioTechnology Suite 100, Croft Hall 3400 North Charles Street Baltimore, md 21218

When designing microfluidic devices, laser scanning microscopes are necessary to view and measure their micron-sized features. PhD candidates, Chrissy O’Keefe and Sarah Friedrich, use the microscopes to view the 3-D surface of a mold of a potential new device.