2021 CAREER Award recipient: Alex Hughes, Assistant Professor in Bioengineering

by Melissa Pappas

Alex Hughes (illustration by Melissa Pappas)

The National Science Foundation’s CAREER Award is given to early-career researchers in order to kickstart their careers in innovative and pivotal research while giving back to the community in the form of outreach and education. Alex Hughes, Assistant Professor in Bioengineering and in Cell and Developmental Biology, is among the Penn Engineering faculty members who have received the CAREER Award this year.

Hughes plans to use the funds to develop a human kidney model to better understand how the development of cells and tissues influences congenital diseases of the kidney and urinary tract.

The model, known as an “organoid,” is a lab-grown piece of human kidney tissue on the scale of millimeters to centimeters, grown from cultured human cells.

“We want to create a human organoid structure that has nephrons, the filters of the kidney, that are properly ‘plumbed’ or connected to the ureteric epithelium, the tubules that direct urine towards the bladder,” says Hughes. “To achieve that, we have to first understand how to guide the formation of the ureteric tubule networks, and then stimulate early nephrons to fuse with those networks. In the end, the structures will look like ‘kidney subunits’ that could potentially be injected and fused to existing kidneys.”

The field of bioengineering has touched on questions similar to those posed by Hughes, focusing on drug testing and disease treatment. Some of these questions can be answered with the “organ-on-a-chip” approach, while others need an even more realistic model of the organ. The fundamentals of kidney development and questions such as “how does the development of nephrons affect congenital kidney and urinary tract anomalies?” require an organoid in an environment as similar to the human body as possible.

“We decided to start with the kidney for a few reasons,” says Hughes. “First, because its development is a beautiful process; the tubule growth is similar to that of a tree, splitting into branches. It’s a complex yet understudied organ that hosts incredibly common developmental defects.

“Second,” he says, “the question of how things form and develop in the kidney has major medical implications, and we cannot answer that with the ‘organ-on-a-chip’ approach. We need to create a model that mimics the chemical and mechanical properties of the kidney to watch these tissues develop.”

The fundamental development of the kidney can also answer other questions related to efficiency and the evolution of this biological filtration system.

“We have the tendency to believe that systems in the human body are the most evolved and thus the most efficient, but that is not necessarily true,” says Hughes. “If we can better understand the development of a system, such as the kidney, then we may be able to make the system better.”

Hughes’ kidney research will lay the foundation for broader goals within regenerative medicine and organ transplantation.

Read the full story in Penn Engineering Today.

Bioengineering Graduate Gabriel DeSantis Awarded Fulbright Grant

Gabriel DeSantis (BSE 2020, MSE 2021)

Congratulations to recent Penn Bioengineering graduate Gabriel DeSantis on being awarded a Fulbright grant for the 2021-22 academic year:

“The Fulbright Program is the United States government’s flagship international educational exchange program, awarding grants to fund as long as 12 months of international experience.

‘As an avenue for building cross-cultural understanding, the U.S. Student Fulbright Program is an unparalleled opportunity for American students to represent our country and our University across the world,’ says Jane Morris, executive director of Penn’s Center for Undergraduate Research and Fellowships, which supports applicants. ‘We are so proud of all our Penn Fulbright students who will be contributing to this important mission through their study, research, and English teaching as Fulbrighters.’

Gabriel DeSantis, from Wellesley, Massachusetts, received his bachelor’s degree from Penn Bioengineering in 2020 and will graduate in May with a master’s degree in bioengineering from the School of Engineering and Applied Science. He was awarded a Fulbright to conduct research in Portugal at the International Iberian Nanotechnology Laboratory. There he will be creating a 3D bio-printed model to optimize the texture and nutritional profiles of cultivated meat. At Penn his academic interests included biology, food science, and sustainability, which he hopes to use to develop new systems of food production. On campus, DeSantis was a Penn Abroad Leader and board member of the Graduate Association of Bioengineers. He is a past chair of the Mask and Wig Club. He currently works as a research assistant for Allevi, a Philadelphia-based bioprinting company at Pennovation Works.”

Read the full list of Fulbright awardees in Penn Today.

Engineering and Medicine Researchers Collaborate on Studies of Genome Folding in Health and Disease

(Left to right) Top row: Jennifer E. Phillips-Cremins, Rajan Jain, and Eric Joyce. Middle row: Melike Lakadamyali, Golnaz Vahedi, and Gerd Blobel. Bottom row: Bomyi Lim, Arjun Raj, and Stanley Qi.

Popular accounts of the human genome often depict it as a long string of DNA base pairs, but in reality the genome is separated into chromosomes that are tightly twisted and coiled into complex three-dimensional structures. These structures create a myriad of connections between sites on the genome that would be distant from one another if stretched out end-to-end. These “long range interactions” are not incidental — they regulate the activity of our genes during development and can cause disease when disrupted.

Now two teams of researchers at the Perelman School of Medicine at the University of Pennsylvania, each led by Jennifer E. Phillips-Cremins,  associate professor and Dean’s Faculty Fellow in the Department of Bioengineering at the School of Engineering and Applied Science and of Genetics at the Perelman School of Medicine have been awarded grants totaling $9 million from the National Institutes of Health (NIH), as part of a major NIH Common Fund initiative to understand such 3D-genomic interactions.

The initiative, known as the 4D Nucleome Program, broadly aims to map higher-order genome structures across space and time, as well as to understand how the twists and loops of the DNA sequence govern genome function and cellular phenotype in health and disease.

Read the full story in Penn Engineering Today.

N.B.: In addition to Phillips-Cremins, collaborators include Arjun Raj, Professor in Bioengineering and Genetics, and Bioengineering Graduate Group Members Melike Lakadamyali, Associate Professor in Physiology, and Bomyi Lim, Assistant Professor in Chemical and Biomolecular Engineering.

Postdoctoral Fellow Linden Parkes Wins BBRF Young Investigator Grant

Linden Parkes, PhD

The Department of Bioengineering at Penn is thrilled to congratulate Linden Parkes on receiving a Brain & Behavior Research Foundation (BBRF) Young Investigator Grant for 2021-2022. This grant will support Parkes’ continued postdoctoral research under the supervision of Danielle S. Bassett, J. Peter Skirkanich Professor of Bioengineering and Electrical and Systems Engineering in the School of Engineering and Applied Science (SEAS),  Theodore D. Satterthwaite, Associate Professor of Psychiatry in the Perelman School of Medicine (PSOM), and Raquel E. Gur, the Karl and Linda Rickels Professor of Psychiatry in PSOM.

Originally from Australia, Parkes did his undergraduate B.Sc. (Hons.) in Psychology and Psychophysiology at the Swinburne University of Technology in Melbourne. He went on to receive his Ph.D. in Neuroscience from the Turner Institute for Brain and Mental Health at Monash University (also in Melbourne) under the supervision of Murat Yucel, Professor of Psychology, Alex Fornito, Professor of Psychology, and Ben Fulcher, Senior Lecturer in the School of Physics at the University of Sydney. After finishing his doctorate, Parkes moved to Philadelphia to take up a position as a postdoctoral fellow in Danielle Bassett’s Complex Systems Lab.

Parkes will use the BBRF’s support to continue his research examining the link between the symptoms of mental illness and the brain. In particular, he seeks to uncover how individual patterns of abnormal neurodevelopment link to, and predict, the emergence of psychosis symptoms through childhood and adolescence using longitudinal data. In turn, Parkes’ work will discover prognostic biomarkers for the psychosis spectrum that will help inform clinical outcome tracking.

“I am honored to have been selected for a Young Investigator Grant from the BBRF this year,” Parkes says. “This award will support me to conduct research that I believe will make real inroads into understanding the pathways that link abnormalities in neurodevelopment to the symptoms of psychosis. I feel grateful for the opportunity to complete my postdoctoral training at Penn. Penn has connected me with wonderful people who I’m sure will be lifelong mentors, colleagues, and peers.”

The BBRF Young Investigator Grants are valued at more than $10.3 million and are awarded annually to 150 of the world’s most promising young scientists to support the work of early career investigators with innovative ideas for groundbreaking neurobiological research seeking to identify causes, improve treatments, and develop prevention strategies for psychiatric disorders.

Read more about the BBRF 2020 Young Investigators here.

Penn Bioengineering’s Tsourkas Lab and Penn Start-up AlphaThera Awarded $667,000 SBIR Phase II Grant to Improve COVID-19 Detection Assays

To combat the COVID-19 pandemic caused by the SARS-CoV2 virus, Dr. Andrew Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine (Titan) Lab in Penn Bioengineering, in collaboration with the Penn-based startup, AlphaThera, was recently awarded a $667,000 SBIR Phase II Grant Extension to support its efforts in commercializing COVID-19 detection technology. The grant supports work to address the growing need for anti-viral antibody testing. Specifically, the Tsourkas Lab and AlphaThera hope to leverage their expertise with antibody conjugation technologies to reduce the steps and complexity of existing detection assays to enable greater production and higher sensitivity tests. AlphaThera was founded in 2016 by Andrew Tsourkas, PhD, Professor of Bioengineering and James Hui, MD, PhD, a graduate of the Perelman School of Medicine and Penn Bioengineering’s doctoral program.

During this pandemic it is crucial to characterize disease prevalence among populations, understand immunity, test vaccine efficacy and monitor disease resurgence. Projections have indicated that millions of daily tests will be needed to effectively control the virus spread. One important testing method is the serological assay: These tests detect the presence of SARS-CoV2 antibodies in a person’s blood produced by the body’s immune system responding to infection. Serological tests not only diagnose active infections, but also establish prior infection in an individual, which can greatly aid in forecasting disease spread and contact tracing. To perform the serological assays for antibody detection, well-established immunoassay methods are used such as ELISA.

A variety of issues have slowed the distribution of these serological assays for antibody testing. The surge in demand for testing has caused shortages in materials and reagents that are crucial for the assays. Furthermore, complexity in some of the assay formats can slow both production and affect the sensitivity of test results. Recognizing these problems, AlphaThera is leveraging its novel conjugation technology to greatly improve upon traditional assay formats.

With AlphaThera’s conjugation technology, the orientation of antibodies can be precisely controlled so that they are aligned and uniformly immobilized on assay detection plates. This is crucial as traditional serological assays often bind antibodies to plates in a non-uniform manner, which increases variability of results and reduces sensitivity. See Fig 1 below. With AlphaThera’s uniform antibody immobilization, assay specificity could increase by as much as 1000- fold for detection of a patient’s SaRS-CoV2 antibodies.

Fig 1: Uniform vs Non-Uniform Immobilized Antibodies on Surface: Top is AlphaThera improvement, showing how antibodies would be uniformly immobilized and oriented on a plate for detection. Bottom is how many traditional serological assays immobilize antibodies, resulting in variability of results and lower specificity.

Furthermore, AlphaThera is addressing the shortage of assay reagents, specifically secondary antibody reagents, by removing certain steps from traditional serological assays. Rather than relying on secondary antibodies for detection of the patient antibodies, AlphaThera’s technology can label the patient SaRS-CoV2 primary antibodies directly in serum with a detection reagent. This eliminates several processing steps, reducing the time of the assay by as much as 50%, as well as the costs.

The Tsourkas Lab and AlphaThera have initiated their COVID-19 project, expanding into the Pennovation Center and onboarding new lab staff. Other antibody labeling products have also become available and are currently being prepared for commercialization. Check out the AlphaThera website to learn more about their technology at https://www.alphathera.com.

NIH SBIR Phase II Grant Extension— 5-R44-EB023750-03 (PI: Yu)  — 10/07/2020 – 10/07/2021

Jennifer Phillips-Cremins Wins CZI Grant to Study 3D Genome’s Role in Neurodegenerative Disease

The Chan Zuckerberg Initiative’s Collaborative Pairs Pilot Project Award is part of its Neurodegeneration Challenge Network

Jennifer Phillips-Cremins, Ph.D.

Read the full story on the Penn Engineering blog.

Dan Huh Receives Chan Zuckerberg Initiative Grant for Placenta-on-a-chip Research

CRI huh
Dan Huh, Ph.D.

The Chan Zuckerberg Initiative (CZI) has announced $14 million in funding to support 29 interdisciplinary teams who are investigating the role of inflammation in disease. Among these recipients is Dan Huh, Associate Professor in Bioengineering, whose placenta-on-a-chip research will “explore how maternal and fetal cells respond to specific inflammatory signals and analyze the network of placental cells and immune cells that impact pregnancy outcomes in chronic inflammatory diseases.”

Kellie Ann Jurado, Presidential Assistant Professor in the Perelman School of Medicine’s Department of Microbiology, will lead the research team. She and Huh will collaborate with Monica Mainigi, William Shippen, Jr. Assistant Professor of Human Reproduction in Penn Medicine.

A version of the Huh Lab’s placenta-on-a-chip from 2018

Huh’s placenta-on-a-chip consists of a small block of silicone containing microfluidic channels separated by a membrane of human cells. Variations in designs and cell types allow researchers to study how different molecules cross that barrier, allowing for experiments that would be otherwise impossible or unethical. For example, Huh and his group previously used a placenta-on-a-chip designed to model the placental barrier to research the effect of maternally-administered medications on the fetal bloodstream.

In this new study, Huh, Jurando and Mainigi were motivated by even more fundamental questions of pregnancy.

“It has been known for quite some time that women with chronic inflammatory diseases are at increased risk of developing various complications during pregnancy,” Huh says. “Despite accumulating clinical evidence, we understand little about how inflammation contributes to adverse pregnancy outcomes.”

Read the full story on the Penn Engineering blog.

BE Senior Design Team Wins Berkman Prize

Senior Design Group MeVR

We would like to congratulate Penn Bioengineering Senior Design team MeVR on winning a Berkman Prize. MeVR consists of current BE seniors Nicole Chiou, Gabriel DeSantis, Ben Habermeyer, and Vera Lee. Awarded by the Penn Engineering Entrepreneurship Program, the Berkman Opportunity Fund provides grants to support students with innovative ideas that might turn into products and companies.

Bioengineering Seniors Ben Habermeyer (top left), Nicole Chiou (top right), Gabriel DeSantis (bottom right), and Vera Lee (bottom left)

MeVR is a bioresponsive virtual reality platform for administering biofeedback therapy. Biofeedback is the process of gaining greater awareness of involuntary physiological functions using sensors that provide information on the activity of those bodily systems, with the goal of gaining voluntary control over functions such as heart rate, muscle tension, and pain perception. This therapy is used to treat a variety of conditions such as chronic pain, stress, anxiety, and PTSD. These treatments cost on the order of hundreds to thousands of dollars, require the presence of a therapist to set up and deliver the therapy session, and are generally not interactive or immersive. MeVR is a platform to reduce these limitations of biofeedback therapy through an individualized, immersive, and portable device which guides users through biofeedback therapy using wearable sensors and a virtual reality environment which responds in real-time to biological feedback from the user’s body.

As part of the two-semester Senior Design course (BE 495 & BE 496), MeVR and the rest of the Bioengineering B.S.E. seniors will continue to develop their projects throughout the remainder of the academic year in George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, culminating in their final presentations and the annual SEAS Senior Design Project Competition at the end of the spring 2020 semester.

 

Lee Bassett and Andrew Tsourkas Awarded Grainger Foundation Grant for Interdisciplinary Research

Lee Bassett and Andrew Tsourkas

By Lauren Salig

The National Academy of Engineering (NAE) has awarded two Penn Engineers with The Grainger Foundation Frontiers of Engineering Grant for Advancement of Interdisciplinary Research. Lee Bassett, assistant professor in the Department of Electrical and Systems Engineering, and Andrew Tsourkas, professor and undergraduate chair in the Department of Bioengineering, will be using the $30,000 award to kick-start their research collaboration.

The NAE describes the Frontiers of Engineering program as one that “brings together outstanding early-career engineers from industry, academia, and government to discuss pioneering technical work and leading-edge research in various engineering fields and industry sectors. The goal is to facilitate interactions and exchange of techniques and approaches across fields and facilitate networking among the next generation of engineering leaders.”

Bassett and Tsourkas fit the grant’s description, as their proposed research requires them to combine their different areas of expertise to push the state of the art in engineering. The pair plans to engineer a new class of nanoparticles that can sense and differentially react to particular chemicals in their biochemical environment. This new class of nanoparticles could allow scientists to better study cellular processes and could eventually have important applications in medicine, potentially allowing for more personalized diagnoses and targeted treatment of disease.

To design and create this type of nanoparticle is no small task. The research demands Bassett’s background in engineering quantum-mechanical systems for use as environmental sensors, and Tsourkas’ ability to apply these properties to nanoscale “theranostic” agents, which are designed to target treatments based on a patient’s specific diagnostic test results.

By combining forces, Bassett and Tsourkas hope to introduce a new nanoparticle tool into their fields and to connect even more people in their different areas to promote future interdisciplinary work.

Originally posted on the Penn Engineering Medium Blog.

Week in BioE (August 16, 2018)

Microscopic Magnets Reduce Pain

A new approach uses “mechanoceuticals” to treat pain.

Drugs are commonly injected directly into an injury site to speed healing. For chronic pain, clinicians can inject drugs to reduce inflammation in painful joints, or can inject nerve blockers to block the nerve signals that cause pain. In a recent study, a group from UCLA developed a technique to deform a material surrounding nerve fibers to trigger a response in the fibers that would relieve pain. The combination of mechanics and treatment – i.e., ‘mechanoceuticals’ – is a clever way to trick fibers and reverse painful symptoms. Done without any injections and simply controlling magnetic fields outside the body, this approach can be reused as necessary.

The design of this mechanoceutical was completed by Dino Di Carlo, PhD, Professor of Bioengineering, and his team at UCLA’s Sameuli School of Engineering. By encasing tiny, magnetic nanoparticles within a biocompatible hydrogel, the group used magnetic force to stimulate nerve fibers and cause a corresponding decrease in pain signals. This promising development opens up a new approach to pain management, one which can be created with different biomaterials to suit different conditions, and delivered “on demand” without worrying about injections or, for that matter, any prescription drugs.

Understanding the Adolescent Brain

It’s no surprise that adults and adolescents often struggle to understand one another, but the work of neurologists and other researchers provides a possible physical reason for why that might be. Magnetic resonance elastrography (MRE) is a tool used in biomedical imaging to estimate the mechanical properties, or stiffness, of tissue throughout the body. Unexpectedly, a recent study suggests that brain stiffness correlates with cognitive ability, suggesting MRE may provide insight into patients’ behavior, psychology, and psychiatric state.

A new paper in Developmental Cognitive Neuroscience published the results of a study using MRE to track the relative “stiffness” vs. “softness” of adult and adolescent brains. The University of Delaware team, led by Biomedical Engineering Assistant Professor Curtis Johnson, PhD, and his doctoral student Grace McIlvain, sampled 40 living subjects (aged 12-14) and compared the properties to healthy adult brains.

The study found that children and adolescent brains are softer than those of adults, correlating to the overall malleability of childhood development. The team hopes to continue their studies with younger and older children, looking to demonstrate exactly when and how the change from softness to stiffness takes place, and how these properties correspond to individual qualities such as risk-taking or the onset of puberty. Eventually, establishing a larger database of measurements in the pediatric brain will help further studies into neurological and cognitive disorders in children, helping to understand conditions such as multiple sclerosis, autism, and cerebral palsy.

Can Nanoparticles Replace Stents?

Researchers and clinicians have made amazing advances in heart surgery. Stents, in particular, have become quite sophisticated: they are used to both prop open clogged arteries as well as deliver blood-thinning medication slowly over days to weeks in the area of the stent. However, the risk of blood clotting increases with stents and the blood vessels can constrict over time after the stent is placed in the vessel.

A recent NIH grant will support the design of a stent-free solution to unclog blood vessels. Led by Shaoqin Gong, PhD, Vilas Distinguished Professor of Biomedical Engineering at UW-Madison, the team used nanoparticles (or nanoclusters) to directly target the affected blood vessels and prevent regrowth of the cells post-surgery, eliminating the need for a stent to keep the pathways open. These nanoclusters are injected through an intravenous line, further reducing the risks introduced by the presence of the stent. As heart disease affects millions of people worldwide, this new material has far-reaching consequences. Their study is published in the September edition of Biomaterials.

NIST Grant Supports

The National Institute of Standards and Technology (NIST) awarded a $30 million grant to Johns Hopkins University, Binghamton University, and Morgan State University as part of their Professional Research Experience Program (PREP). Over five years, this award will support the collaboration of academics from all levels (faculty, postdoc, graduate, and undergraduate) across the three universities, enabling them to conduct research and attend NIST conferences.

The principal investigator for Binghamton U. is Professor and Chair of the Biomedical Engineering Department, Kaiming Ye, PhD. Dr. Ye is also the Director of the Center of Biomanufacturing for Regenerative Medicine (CBRM), which will participate in this collaborative new enterprise. Dr. Ye hopes that this grant will create opportunities for academics and researchers to network with each other as well as to more precisely define the standards for the fields of regenerative medicine and biomaterial manufacturing.

People and Places

The A. James Clark Scholars Program has been established in the School of Engineering and Applied Science at the University of Pennsylvania with an extraordinary $15 million gift from the A. James & Alice B. Clark Foundation. It is the largest one-time gift to undergraduate support in the University’s history. The Clark Scholars Program will provide financial aid and create a new academic program for undergraduate engineering students.

The gift honors the late A. James Clark, former CEO of Clark Enterprises and Clark Construction Group LLC, one of the country’s largest privately-held general building contractors. It is designed to prepare future engineering and business leaders, with an emphasis on low income families and first-generation college students. Clark never forgot that his business successes began with an engineering scholarship. This has guided the Clark family’s longstanding investments in engineering education and reflects its commitment to ensure college remains accessible and affordable to high-potential students with financial need.

Read the full story at Penn Today. Media contact Evan Lerner and Ali Sundermier.

We are proud to say that three incoming Clark Scholars from the Freshman Class of 2022 will be part of the Bioengineering Department here at Penn.

And finally, our congratulations to the new Dean of the School of Engineering at the University of Mississippi: David A. Puleo, PhD. Dr. Puleo earned his bachelor’s degree and doctorate in Biomedical Engineering from Rensselaer Polytechnic Institute. Most recently he served as Professor of Biomedical Engineering and Associate Dean for Research and Graduate Studies at the University of Kentucky’s College of Engineering. Building on his research in regenerative biomaterials, he also founded Regenera Materials, LLC in 2014. Over the course of his career so far, Dr. Puleo received multiple teaching awards and oversaw much departmental growth within his previous institution, and looks poised to do the same for “Ole Miss.”