University of Notre Dame Bioengineering Annual Review/2019

2019 ANNUAL REVIEW

IN THIS ISSUE From the Director . . . . . . . . . . . . . . 2 Faculty News . . . . . . . . . . . . . . . . . . . 3 Student Spotlights . . . . . . . . . . . . . 6 Alumni Spotlights . . . . . . . . . . . . . . 7 Participating Faculty . . . . . . . . . . . 8

Weber Receives 2019 3M Non-tenured Faculty Award Earlier this year Matthew J. Webber, assistant professor of chemical and biomolecular engineering at the University of Notre Dame, was named a recipient of the 2019 3M Non-tenured Faculty Award. Presented annually by 3M’s Research and Development Community in partnership with 3Mgives, the award recognizes young faculty who excel in research, experience, and academic leadership. It also includes an invitation to 3M’s Science & Engineering Faculty Day. Webber’s work focuses on supramolecular biomaterials, “smart” drug delivery and diagnostics, bioinspired materials, and supramolecular chemistry in order to develop novel healthcare strategies and devices for improved therapeutics, including the tailoring of materials with

predictable and tunable properties.

A faculty member since 2016, he holds appointments in the Department of Chemistry and Biochemistry, Mike and Josie Harper Cancer Research Institute, Advanced Diagnostics and Therapeutics at Notre Dame, Warren Family Research Center for Drug Discovery and Development, and the University’s Center for Nano Science and Technology.

In addition to the 3M award, he was recently honored with the American Diabetes Association’s Accelerator 1

Award. In 2017, Webber was named “One of 35 Under 35” by the American Institute of Chemical Engineers and was selected as one of the Emerging Investigators by Biomaterials Science.

He also received the National Institutes of Health Ruth L. Kirschstein National Research Service Award in 2013, the Dudley Childress Award in 2012 from Northwestern University, and the Acta Biomaterialia Student Award in 2011.

For more information on Professor Webber’s work in supramolecular engineering, visit webberlab.com.

From the Director The Notre Dame Bioengineering program has completed another successful year of research and graduate education. In this annual update, we are highlighting the achievements of some of our young faculty, who continue to gain accolades from funding agencies and through society awards. This year, Pinar Zorlutuna was honored with a Presidential Early Career Award for Scientists and Engineers. She was also promoted from assistant to associate professor with tenure in the Department of Aerospace and Mechanical Engineering. Assistant Professor Matt Webber received a 3M Non-tenured Faculty Award in recognition of his efforts in the laboratory and the classroom. In addition, Assistant Professor Donny Hanjaya-Putra received a Career Development Award from the American Heart Association for his work studying the use of biomaterials and stem cells to regenerate the lymphatic system for therapeutic applications, and Assistant Professor Maria Holland received a National Science Foundation Computer and Information Science and Engineering Research Initiative grant as she continues her work in the computational modeling and analysis of brain development.

Collaborations with biologists and biochemists, on and off campus, have been a major driver of new research. At the same time, new collaborations have been forged with our colleagues in physics and engineering, emphasizing the cross-cutting nature of bioengineering research and education. Some examples include imaging technologies (ranging from nanoparticle contrast agents to superresolution microscopy), mechanobiology of metastasis, tissue-on-a-chip systems, and microfluidic analytical devices. We are also fortunate to be associated with the Indiana Clinical and Translational Sciences Institute, a National Institutes of Health supported institute. This institute has been the catalyst for multiple collaborations with researchers at Purdue and the Indiana University School of Medicine through seed grants and access to core facilities, further fostering the collaborative approach and breadth of our program.

We have developed several industry collaborations that are leading to commercialization opportunities. In particular, a second Notre Dame team was awarded an Advanced Regenerative Manufacturing Institute project, with multiple industry collaborations. This broad research portfolio offers opportunities for students with career paths in industry, government, and academia.

Several of these collaborations and programs are highlighted later in this newsletter.

Currently, we have 24 Ph.D. students who are advised by 11 different engineering faculty members across three departments. Several students are co-advised by engineering and science faculty. We are welcoming seven new students to the program this fall and look forward to integrating them into our research community.

At the same time we welcome new students, we say farewell to five Ph.D. students, who graduated over the past calendar year. They have gone on to postdoctoral positions at Princeton and Harvard and to companies such as Exponent. Part of our ninth graduating class, they are the best indicators of the depth of our program as they hold a wide range of academic and industry positions across the country.

We are continually striving to be a hub for engineering applications in the life sciences at Notre Dame and are looking forward to a new year of exciting research and discovery.

Glen L. Niebur Professor, Aerospace and Mechanical Engineering Bioengineering Graduate Program Director Phone: 574.631.3327 Email: gniebur@nd.edu 2

Faculty News $2.9 NIH Grant Targets Timelines for Cancer Diagnoses Researchers at the University of Notre Dame have received $2.9 million to develop a new diagnostic platform that could identify cancer in as little as three hours by using only one or two drops of blood.

With the award from the National Institutes of Health, the research team will begin integrating a suite of micro- or nanofluidic technologies to improve the analysis of extracellular RNA (exRNA), which are molecules critical to disease development. The role of exRNA is to carry information about cellular makeup. Therefore, the release of exRNA from tumor cells may offer important details such as tumor type and size.

The new diagnostic platform aims to separate nanoparticle carriers from their exRNAs and to identify the different carriers of exRNA, in order to decipher the “information” these exRNAs carry and pinpoint their cell origin.

Go, the Rooney Family Collegiate Professor in the Department of Aerospace and Mechanical Engineering, for pancreatic and liver cancers.

Chang, along with Ceming Wang, postdoctoral scholar in the Chang lab, and Larry Cheng, associate professor of electrical and computer engineering at Oregon State University and former postdoctoral scholar at Notre Dame, previously invented nanofluidic technologies that actually separate the nanoparticles. Go also worked with Senapati and Chang on a technology that releases the exRNA from sorted nanoparticles by using surface acoustic waves.

“Current technology has allowed for the identification of exRNA, but slowly, and the results are typically inefficient and lack the quality needed to determine a diagnosis,” said Hsueh-Chia Chang, the Bayer Professor of Chemical and Biomolecular Engineering and project lead. “Our proposed diagnostic platform will separate the nanoparticle carriers, release their exRNA cargo, and then identify the disease biomarkers, all by integrating an array of technologies invented by our research team here at Notre Dame.”

Melanoma cells surrounded by shed extracellular vesicles. Photo courtesy of Alanna Sedgwick, D’Souza-Schorey Laboratory.

Crislyn D’Souza-Schorey, the Morris Pollard Professor and Chair in the Department of Biological Sciences, is the cancer biologist on the team. She provides research experience in understanding the transport and roles of exRNAs to the project. Her work on the biological processes of how cancer spreads will be essential for scaling up the previously developed technologies as a holistic diagnostic platform.

With this new funding, the Notre Dame researchers will integrate technologies and expertise to more efficiently identify and quantify biomarkers for multiple types of cancer. The interdisciplinary research team is affiliated with Notre Dame’s Harper Cancer Research Institute and the Advanced Diagnostics and Therapeutics initiative.

The diagnostic platform builds on technologies Chang developed with Satyajyoti Senapati, research assistant professor in chemical and biomolecular engineering, and David

For more information on Notre Dame research in extracellular vesicles, visit www3.nd.edu/~changlab.

About the ND Bioengineering Graduate Program The Bioengineering Graduate Program at Notre Dame is an interdisciplinary Ph.D. program based in the College of Engineering. It encompasses faculty from across the University with expertise in biomaterials, cancer, computational and systems biology, drug delivery and therapeutics, environmental science, genomics/DNA/RNA, health robotics and technology, imaging, mechanobiology and physical effects on cells, orthopaedics, regenerative medicine, rehabilitation and motor control, and sensors and diagnostics. For information about the Notre Dame Bioengineering Program, visit bme.nd.edu.

3

Faculty News continued

CoMMaND Lab Receives $172K to Continue Brain Development Studies

The human brain, the most complex and least understood organ, plays a major role in every body system. Due to the recent proliferation of large public neuroimaging data repositories, researchers have access to an unprecedented amount of data concerning the brain. In many ways, however, the amount of data has surpassed researchers’ abilities to analyze it. With pressing health questions attracting the interest of scientists, clinicians, and engineers, there is an urgent need for computational tools that integrate the methods and expertise of different fields.

This is the need that Maria Holland, the Clare Boothe Luce Assistant Professor of Aerospace and Mechanical Engineering and director of the Computational Mechanics of Morphology at Notre Dame lab (CoMMaND), and her team are addressing. Their most current project, which was awarded $172,879 through the National Science Foundation’s Computer Information Science and Engineering Research Initiation Initiative, seeks to advance the analysis of big brain data by developing, using, and sharing novel open-source computational tools for the modeling and analysis of cortical thickness, an indicator of healthy brain development. Through the analysis of two large data sets containing more than 500 individual scans, a baseline for cortical thickness variation throughout healthy development will be generated.

Numerical simulations will also shed light on the effect of the mechanical forces that give rise to the brain’s unique shape.

The computational tools developed in the CoMMaND lab will be made available for use by other researchers to further leverage existing open access databases of MRI scans. Beyond that, this project has the potential to produce new insights with clinical applications in the analysis of neurological disorders such as ASD, Alzheimer’s Disease, and Parkinson’s Disease. Alongside this trans-disciplinary project, Holland and her team are developing a studentwritten blog for the general public (sites.nd.edu/biomechanics-in-the-wild), which focuses on interesting investigations in the field of biomechanics.

For more information on brain development studies, visit commandlab.nd.edu.

Zorlutuna Receives 2019 PECASE Pinar Zorlutuna, the Sheehan Family Associate Professor of Engineering, was named one of the recipients of the 2019 Presidential Early Career Award for Scientists and Engineers (PECASE).

myocardial infarction, tissue aging, and breast cancer.

She has received a number of awards as a young faculty member. Most recently, in 2017 she received the National Science Foundation’s CAREER Award. In 2016, she was one of six young researchers selected to receive the “Rising Star” Award from the Biomedical Engineering Society.

In addition to her work in the Department of Aerospace and Mechanical Engineering and with the Notre Dame Bioengineering program, Zorlutuna is an affiliated faculty member of Notre Dame’s Advanced Diagnostics and Therapeutics Initiative and the Mike and Josie Harper Cancer Research Institute.

A faculty member since 2014, Zorlutuna explores the design of biomimetic environments to understand and control cell behavior, as well as cell-to-cell and cell-to-environment interactions through tissue engineering, genetic engineering, and micro- and nanotechnology. Leveraging her extensive experience in tissue engineering, biomaterials, stem cells, and microfabrication, Zorlutuna creates tissue and disease models in order to address clinically important problems such as

To find out more about Zorlutuna and her research, visit tissueeng.nd.edu.

4

Notre Dame Bioengineering Leading Two ARMI Projects Notre Dame Bioengineering graduate students and faculty are engaged in two projects sponsored by BioFabUSA (armiusa.org), a program of the Advanced Regenerative Manufacturing Institute (ARMI). BioFabUSA, under the auspices of Department of Defense (DoD), is one of 14 Manufacturing Innovation Institutes authorized by the federal government as part of the Manufacturing USA Network (manufacturingusa.com/).

Veral, physics; Glen Niebur, aerospace and mechanical engineering; and Pinar Zorlutuna, aerospace and mechanical engineering, at Notre Dame.

Advances in Tissue Engineering and Regenerative Medicine (TERM) have the potential to repair injured tissues, overcome a shortage of donor organs, and facilitate novel drug development, thereby enhancing health care and enabling new treatments for previously intractable injuries and diseases. The mission of ARMI|BioFabUSA is to make the scalable, consistent, and cost-effective manufacturing of engineered tissues and tissue-related technologies practical and to benefit existing industries and grow new ones.

A second critical need for the TERM industry is the rapid, robust, and non-invasive in-line monitoring of biomolecules produced by cells during the course of tissue and organ development. Earlier this year, a second Notre Dame team was approved for a $2.8 million BioFabUSA project to develop an automated process analytic technology for in-line monitoring of protein biomarkers to monitor maturation of TERM products at low cost and short detection time.

This multidisciplinary research team is led by Hsueh-Chia Chang (CBE), and includes Satyajyoti Senapati (CBE), Donny Hanjaya-Putra (BioE/AME), and Tengfei Luo (AME), in addition to industrial partners EpiBone, Vascugen, Cellink, and FCubed. By the end of this two-year BioFabUSA project, the team hopes to deliver a prototype of the multiplexed process analytic technologies, which will be tested in industrial bioreactors to monitor tissue-engineered bone at EpiBone, as well as stem cell-derived blood vessels at Vascugen. The team will also work with Cellink and FCubed to scale-up and commercialize the final products.

Notre Dame is engaged in a $3.2 million BioFabUSA project in collaboration with Louisiana State University, The University of Texas at Arlington, and Johnson & Johnson to develop an automated cell expansion bioreactor for incorporation into a TERM production line. TERM products require enormous numbers of multipotent or pluripotent cells that can be seeded into appropriate biomaterials or decellularized matrix in order to form new functional tissues. Expansion of cells can be one of the largest expenses for TERM products, and current methods are not well developed. The goal of the project is to develop a reactor to produce cells on demand, at low cost, and with minimal human intervention. The project is being led by Professors Richard Billo, computer science and engineering; Dervis Can

Funding agencies:

1 National Science Foundation GRF

NIH, NSF, American Heart Association, ARMI, Craig H. Neilsen Foundation, DARPA, Juvenile Diabetes Research Foundation, Kelly Cares Foundation, Walther Cancer Foundation

2 Fulbright Fellowships 1 China Scholarship Council Fellowship 1 Science Foundation Ireland Visiting Fellowship 2 Whitaker Fellowships

Awards: Laura Alderfer — Lymphatic Forum Travel Award 2019 from Lymphatic Education & Research Network (LE&RN)

7 Countries 13 Women

3 Engineering Departments

24 Students

Kimberly Curtis — ORS Collaborative Exchange Award

11 Men

Commercialization and corporate partners: Cubed Laboratories, Happe Spine LLC, IBM, Johnson & Johnson, Mars Bioimaging, Merck, Spinesmith LLC 5

11 Laboratories

Student Spotlights neoadjuvant chemotherapy, and the diagnosis of ischemic and hemorrhagic stroke.

The Bioengineering Graduate program at Notre Dame provides an exceptionally interdisciplinary environment for students throughout the College of Engineering. Ola Abdalsalam, for example, is pursuing her doctorate in bioengineering through the Department of Electrical Engineering. “I work in the field of diffuse optical imaging (DOI), a non-invasive optical imaging technique that uses near-infrared light to capture images of tissue,” she said.

Since DOI can measure chromophore concentrations in tissues, such as hemoglobin, water, and lipids, it is useful in the diagnosis of breast and brain tumors, evaluations of the therapeutic response of breast cancer patients undergoing

Abdalsalam is working to develop a new and more convenient technique for DOI based on creating distinct illumination patterns inside the tissue using the interference of photon density waves. Her goal is to be able to generate more accurate information about the specific tissue composition, which in conjunction with the structural imaging modalities of a mammogram or MRI, can eliminate the need for a biopsy.

Co-advisers Associate Professor Scott Howard and Assistant Professor Thomas O’Sullivan, are providing additional insights to Abdalsalam as she continues her work. “My advisers each have a particular focus — one in diffuse optics and the other in microscopy. This blending of the two worlds of optical imaging gives me a unique perspective that’s proving very valuable.”

A graduate research assistant in the Tissue Mechanics Laboratory, Kimberly Curtis has been able not only to tailor her research to her interests but also to take advantage of the many collaborative opportunities within the Bioengineering Graduate Program. Most recently, she received the Leiva Graduate Fellowship in Precision Medicine from Advanced Diagnostics & Therapeutics at Notre Dame and was awarded an Orthopaedic Research Society Collaborative Exchange Grant.

where she worked on a cutting-edge project with the collaborator, Professor Laoise McNamara. While there Curtis studied how the biophysical environment affects 3D cancer cell growth and migration. Using a custom bioreactor developed at NUIG, she mechanically compressed hydrogel constructs containing breast cancer cells to study how the cancer cells responded to both stiffness of the hydrogel and the compressive loading applied. The work integrated perfectly with her overall dissertation research, which was focused on identifying how the local mechanical environment influences breast cancer metastasis to bone.

According to her adviser Professor Glen Niebur, Curtis has been integral to multiple collaborations — at Memorial Hospital and the Harper Cancer Research Institute in South Bend — investigating biochemical and mechanical factors that might influence breast cancer cell behavior.

This funding allowed her the opportunity to spend six months as a visiting research scholar in the Biomechanics Research Center at the National University of Ireland-Galway (NUIG),

uses theoretical and computational models to better understand how different impedance-based biosensors, such as nanopores and ion-selective membranes, work.

The main goal of the lab is to develop biosensors for early cancer detection.

Upon completion of his Ph.D., Sebastian Sensale, a graduate student in the Department of Aerospace and Mechanical Engineering, plans on staying in academia and continuing his work at the intersection of fundamental and applied research. “I believe that early detection of diseases is essential for the future of healthcare,” he said. “For that reason, I’d like to contribute as much as possible toward advancing DNA sensing and sequencing.”

Sensale’s efforts there focus on the optimization of solidstate nanopores for nucleic acid sensing and sequencing.

“Nanopores are small holes drilled in an insulating membrane,” he said. “Through the detection of changes in the electrical current produced as biomolecules like DNA and RNA cross through this hole, we can count and, hopefully, characterize individual molecules.” The ability to sequence DNA and RNA at the single-molecule level has broad applications to healthcare, from basic research to precision clinical diagnoses of a variety of diseases.

Sensale works in the lab of Bayer Professor of Chemical and Biomolecular Engineering Hsueh-Chia Chang, where he

6

Alumni Spotlights As a graduate student, Aylin Acun was part of the research team in the Zorlutuna Lab. She designed and developed primary and stem cell-based myocardial tissue models using a variety of materials in order to better understand and control the microenvironmental cues, cell-extracellular matrix interactions, and cell-to-cell interactions that occur within the body. Using techniques such as CRISPR/Cas9 gene editing, she studied the effects of aging and reperfusion injury conditions on tissue survival, function, and failure.

Acun completed her Ph.D. in May 2018 and joined the Center for Engineering in Medicine (CEM) at Massachusetts General Hospital-Harvard Medical School as a postdoctoral research fellow. Her current work on large-scale vascularized tissue and

In 2007 when we established the Bioengineering Graduate Program, we wanted to provide an educational experience for graduate students who would be working at the interfaces of engineering, biology, and medicine ... students who would make an impact in the biomedical community. Jacqueline Garrison was one of the first students to graduate from our program. As a graduate student she studied trabecular bone in osteoporotic animal models to understand the competing toughening mechanisms of trabecular density and architecture versus microdamage. She did this by evaluating the trabecular architecture, developing and implementing strain-based multi-axial loading scenarios and quantifying microdamage initiation and propagation. She has certainly put the experiences she gained while at Notre Dame to use.

whole organ engineering is geared toward clinical applications, such as repurposing whole human organs that have been rejected for transplantation. The organs with which she works, although not approved for transplants, can still be used (through decellularization and repopulation with induced pluripotent stem cells) for patient-specific organ engineering.

Working at CEM has proven a good fit for Acun. During her first year there, she received a Shriners Children’s Hospital Postdoctoral Research Fellowship to develop vascularized skin grafts for large-scale skin transplantation.

She credits her time at Notre Dame and in the Bioengineering program — especially the highly collaborative and supportive environment in the Zorlutuna Lab and among all other bioengineering faculty and graduate students — for helping her make a smooth transition to the next step in her career.

platforms. Her duties include driving the innovation and successful strategic development and execution of engineering projects and organizational initiatives within the portfolios.

She is also a vice chair and committee member of multiple associate resource groups within the company focusing on inclusion and diversity.

Prior to joining BD Medical, Garrison worked as a non-clinical bench testing manager at Cook Research Institute in West Lafayette, Indiana. At Cook she supported technical evidence creation for Class III device submissions to the FDA and other global regulatory bodies for product launches within the Aortic Intervention and Peripheral Intervention platforms. Her other work at Cook included the development and implementation of novel, accredited validation methods based on ASTM standards, ISO standards, and FDA guidances for GLP non-clinical testing of medical devices.

In 2016 she signed with the Becton Dickinson and Company (BD Medical) team in Sandy, Utah, where she currently serves as a research and development program manager responsible for the company’s Sustaining Engineering portfolio, which includes three Peripheral Intervention Vascular Catheter

Alumni news spotlights We love to hear from our alumni. Please send information about new positions, honors, awards, and more to Professor Glen Niebur at gniebur@nd.edu.

7

Bioengineering Graduate Program University of Notre Dame 153 Multidisciplinary Research Building Notre Dame, IN 46556-4634 bme.nd.edu

Participating Faculty Biomaterials Donny Hanjaya-Putra Maria Holland Ryan Roeder Tim Ovaert Joshua Shrout Matthew Webber Cancer Hsueh Chia Chang Glen Niebur Ryan Roeder Sharon Stack Sangpil Yoon Computational Biology and Bioinformatics Greg Madey Tijana Milenkovic Drug Delivery/Therapeutics Basar Bilgicer Hsueh Chia Chang Donny Hanjaya-Putra Ryan Roeder Matthew Webber Sangpil Yoon Environmental Science Robert Nerenburg Joshua Shrout

Genomics, DNA, RNA Gregory Timp Health Robotics and Technology James Schmiedeler Patrick Wensing Imaging Paul Bohn Danny Chen Scott Howard Thomas O’Sullivan Ryan Roeder Bradley Smith Sangpil Yoon Mechanobiology and Physical Effects on Cells Donny Hanjaya-Putra Maria Holland Glen Niebur Sangpil Yoon Pinar Zorlutuna Orthopaedics Glen Niebur Tim Ovaert Matt Ravosa Ryan Roeder Joshua Shrout

Regenerative Medicine Donny Hanjaya-Putra Glen Niebur Gregory Timp Matthew Webber Sangpil Yoon Jeremiah Zartman Pinar Zorlutuna Rehabilitation and Motor Control James Schmiedeler Patrick Wensing Sensors and Diagnostics Basar Bilgicer Paul Bohn Hsueh Chia Chang David Go Thomas O’Sullivan Joshua Shrout Bradley Smith Sangpil Yoon