Category: faculty

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Penn Bioengineers Develop Implantable Living Electrodes

Living Electrode Panels (image courtesy of the Cullen Lab)

Connecting the human brain to electrical devices is a long-standing goal of neuroscientists, bioengineers, and clinicians, with applications ranging from deep brain stimulation (DBS) to treat Parkinson’s disease to more futuristic endeavors such as Elon Musk’s NeuraLink initiative to record and translate brain activity. However, these approaches currently rely on using implantable metallic electrodes that inherently provoke a lasting immune response due to their non-biological nature, generally complicating the reliability and stability of these interfaces over time. To address these challenges, D. Kacy Cullen, Associate Professor in Neurosurgery and Bioengineering, and Dayo Adewole, a doctoral candidate in Bioengineering, worked with a multi-disciplinary team of collaborators to develop the first “living electrodes” as an implantable, biological bridge between the brain and external devices. In a recent article published in Science Advances, the team demonstrated the fabrication of hair-like microtissue comprised of living neuronal networks and bundled tracts of axons — the signal sending fibers of the nervous system — protected within soft hydrogel cylinders. They showed that these axon-based living electrodes could be fully controlled and monitored with light — thus eliminating the need for electrical contact — and are capable of surviving and forming synapses with the brain as demonstrated in an adult rat model. While further advancements are necessary prior to clinical use, the current findings provide the foundation for a new class of “living electrodes” as a biological intermediary between humans and devices capable of leveraging natural mechanisms to potentially provide a stable interface for clinical applications.

Cullen has a primary appointment in the Department of Neurosurgery in the Perelman School of Medicine, with a secondary appointment in the Department of Bioengineering in the School of Engineering and Applied Science, and an appointment in the Corporal Michael J. Crescenz VA Medical Center in Philadelphia.

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Penn Engineering and CHOP Researchers Identify Nanoparticles that Could Be Used in Therapeutic mRNA Delivery before Birth

by Evan Lerner

William H. Peranteau, Michael J. Mitchell, Margaret Billingsley, Meghana Kashyap, and Rachel Riley (Clockwise from top left)

Researchers at Children’s Hospital of Philadelphia and the School of Engineering and Applied Science at the University of Pennsylvania have identified ionizable lipid nanoparticles that could be used to deliver mRNA as part of fetal therapy. The proof-of-concept study, published today in Science Advances, engineered and screened a number of lipid nanoparticle formulations for targeting mouse fetal organs and has laid the groundwork for testing potential therapies to treat genetic diseases before birth.

“This is an important first step in identifying nonviral mediated approaches for delivering cutting-edge therapies before birth,” said co-senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at CHOP. “These lipid nanoparticles may provide a platform for in utero mRNA delivery, which would be used in therapies like fetal protein replacement and gene editing.”

Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, is the other co-senior author of the study. The co-first authors are Mitchell Lab members Rachel Riley, a postdoctoral fellow, and Margaret Billingsley, a graduate student, and Peranteau Lab member Meghana Kashyap, a research fellow.

Recent advances in DNA sequencing technology and prenatal diagnostics have made it possible to diagnose many genetic diseases before birth. Some of these diseases are treated by protein or enzyme replacement therapies after birth, but by then, some of the damaging effects of the disease have taken hold. Thus, applying therapies while the patient is still in the womb has the potential to be more effective for some conditions. The small fetal size allows for maximal therapeutic dosing, and the immature fetal immune system may be more tolerant of replacement therapy.

Read the full story in Penn Engineering Today.

NB: Rachel Riley is now Assistant Professor in Biomedical Engineering at Rowan University.

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Studying ‘Hunters and Busybodies,’ Penn and American University Researchers Measure Different Types of Curiosity

by Melissa Pappas

Knowledge networks were created as participants browsed Wikipedia, where pages became nodes and relatedness between pages became edges. Two diverging styles emerged — “the busybody” and “the hunter.” (Illustrations by Melissa Pappas)

Curiosity has been found to play a role in our learning and emotional well-being, but due to the open-ended nature of how curiosity is actually practiced, measuring it is challenging. Psychological studies have attempted to gauge participants’ curiosity through their engagement in specific activities, such as asking questions, playing trivia games, and gossiping. However, such methods focus on quantifying a person’s curiosity rather than understanding the different ways it can be expressed.

Efforts to better understand what curiosity actually looks like for different people have underappreciated roots in the field of philosophy. Varying styles have been described with loose archetypes, like “hunter” and “busybody” — evocative, but hard to objectively measure when it comes to studying how people collect new information.

A new study led by researchers at the University of Pennsylvania’s School of Engineering and Applied Science, the Annenberg School for Communication, and the Department of Philosophy and Religion at American University, uses Wikipedia browsing as a method for describing curiosity styles. Using a branch of mathematics known as graph theory, their analysis of curiosity opens doors for using it as a tool to improve learning and life satisfaction.

The interdisciplinary study, published in Nature Human Behavior, was undertaken by Danielle Bassett, J. Peter Skirkanich Professor in Penn Engineering’s Departments of Bioengineering and Electrical and Systems Engineering, David Lydon-Staley, then a post-doctoral fellow in her lab, now an assistant professor in the Annenberg School of Communication, two members of Bassett’s Complex Systems Lab, graduate student Dale Zhou and postdoctoral fellow Ann Sizemore Blevins, and Perry Zurn, assistant professor from American University’s Department of Philosophy.

“The reason this paper exists is because of the participation of many people from different fields,” says Lydon-Staley. “Perry has been researching curiosity in novel ways that show the spectrum of curious practice and Dani has been using networks to describe form and function in many different systems. My background in human behavior allowed me to design and conduct a study linking the styles of curiosity to a measurable activity: Wikipedia searches.”

Zurn’s research on how different people express curiosity provided a framework for the study.

Read the full story in Penn Engineering Today.

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One Step Closer to an At-home, Rapid COVID-19 Test

Created in the lab of César de la Fuente, this miniaturized, portable version of rapid COVID-19 test, which is compatible with smart devices, can detect SARS-CoV-2 within four minutes with nearly 100% accuracy. (Image: Courtesy of César de la Fuente)

The lab of Penn’s César de la Fuente sits at the interface of machines and biology, with much of its work focused on innovative treatments for infectious disease. When COVID-19 appeared, de la Fuente and his colleagues turned their attention to building a paper-based biosensor that could quickly determine the presence of SARS-CoV-2 particles from saliva and from samples from the nose and back of the throat. The initial iteration, called DETECT 1.0, provides results in four minutes with nearly 100% accuracy.

Clinical trials for the diagnostic began Jan. 5, with the goal of collecting 400 samples—200 positive for COVID-19, 200 negative—from volunteers who also receive a RT-PCR or “reverse transcription polymerase chain reaction” test. This will provide a comparison set against which to measure the biosensor to determine whether the results the researchers secured at the bench hold true for samples tested in real time. De la Fuente expects the trial will take about a month.

If all goes accordingly, he hopes these portable rapid breath tests could play a part in monitoring the COVID status of faculty, students, and staff around Penn.

César de la Fuente earned his bachelor’s degree in biotechnology, then a doctorate in microbiology and immunology and a postdoc in synthetic biology and computational biology. Combining these fields led him to the innovative work his lab, the Machine Biology Group, does today. (Photo: Eric Sucar)

Taking on COVID-19 research in this fashion made sense for this lab. “We’re the Machine Biology Group, and we’re interested in existing and emerging pathogens,” says de la Fuente, who has appointments in the Perelman School of Medicine and School of Engineering and Applied Science. “In this case, we’re using a machine to rapidly detect SARS-CoV-2.”

To this point in the pandemic, most SARS-CoV-2 diagnostics have used RT-PCR. Though effective, the technique requires significant space and trained workers to employ, and it is costly and takes hours or days to provide results. De la Fuente felt there was potential to create something inexpensive, quicker, and, perhaps most importantly, scalable.

Continue reading “One Step Closer to an At-home, Rapid COVID-19 Test,” by Michele Berger, at Penn Today.

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Penn, Carnegie Mellon and Johns Hopkins to Develop New Turing Tests, Investigate How AI Can Become More Like Biological Intelligence

by Evan Lerner

While artificial intelligence is becoming a bigger part of nearly every industry and increasingly present in everyday life, even the most impressive AI is no match for a toddler, chimpanzee, or even a honeybee when it comes to learning, creativity, abstract thinking or connecting cause and effect in ways they haven’t been explicitly programmed to recognize.

This discrepancy gets at one of the field’s fundamental questions: what does it mean to say an artificial system is “intelligent” in the first place?

Konrad Kording, Timothy Verstynen, Joshua T. Vogelstein, and Leyla Isik (clockwise from top left)

Seventy years ago, Alan Turing famously proposed such a benchmark; a machine could be considered to have artificial intelligence if it could successfully fool a person into thinking it was a human as well. Now, many artificial systems could pass a “Turing Test” in certain limited domains, but none come close to imitating the holistic sense of intelligence we recognize in animals and people.

Understanding how AI might someday be more like this kind of biological intelligence — and developing new versions of the Turing Test with those principles in mind — is the goal of a new collaboration between researchers at the University of Pennsylvania, Carnegie Mellon University and Johns Hopkins University.

The project, called “From Biological Intelligence to Human Intelligence to Artificial General Intelligence,” is led by Konrad Kording, a Penn Integrates Knowledge Professor with appointments in the Departments of Bioengineering and Computer and Information Science in Penn Engineering and the Department of Neuroscience at Penn’s Perelman School of Medicine. Kording will collaborate with Timothy Verstynen of Carnegie Mellon University, as well Joshua T. Vogelstein and Leyla Isik, both of Johns Hopkins University, on the project.

Read the full story on Penn Engineering Today.

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Bioengineering Faculty Contribute to New Treatment That “Halts Osteoarthritis-Like Knee Cartilage Degeneration”

A recent study published in Science Translational Medicine announces a discovery which could halt cartilage degeneration caused by osteoarthritis: “These researchers showed that they could target a specific protein pathway in mice, put it into overdrive and halt cartilage degeneration over time. Building on that finding, they were able to show that treating mice with surgery-induced knee cartilage degeneration through the same pathway via the state of the art of nanomedicine could dramatically reduce the cartilage degeneration and knee pain.” This development could eventually lead to treating osteoarthritis with injection rather than more complicated surgery.

Among a team of Penn Engineering and Penn Medicine researchers, the study was co-written by Zhiliang Cheng, Research Associate Professor in Bioengineering, Andrew Tsourkas, Professor in Bioengineering, and Ling Qin, Associate Professor of Orthopaedic Surgery in the Perelman School of Medicine and member of the Bioengineering Graduate Group. The lead author was Yulong Wei of the Department of Orthopaedic Surgery and the McKay Orthopaedic Research Laboratory.

Read the press release in Penn Medicine News.

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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.

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Penn Bioengineering’s Applicant-Support Program Supports “Underserved and Underrepresented Communities”

A recent piece in the Daily Pennsylvanian highlights Penn Bioengineering’s new Applicant-Support Program. Introduced for the Fall 2020 admissions cycle, this new program supports the department’s mission of increasing diversity, equity, and inclusion by pairing Ph.D. applicants to current doctoral students who will serve as a mentors to help navigate the process, give feedback on application materials, and provide other support to prospective students.

As Jason Andrechak, President of Penn’s Graduate Association of Association of Bioengineers (GABE) chapter, explains in the DP’s profile: “A lot of what a successful application looks like at this level is just knowing what a successful application looks like.” This and other new policies and programs implemented by GABE and Yale Cohen, Professor of Otorhinolaryngology, Neuroscience and Bioengineering and BE’s current Graduate Group Chair, seek to support applications from “underserved or underrepresented communities.”

Read the full story in the Daily Pennsylvanian.

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Danielle Bassett and Jason Burdick are Among World’s Most Highly Cited Researchers

Danielle Bassett and Jason Burdick
Danielle Bassett and Jason Burdick

The nature of scientific progress is often summarized by the Isaac Newton quotation, “If I have seen further it is by standing on the shoulders of giants.” Each new study draws on dozens of earlier ones, forming a chain of knowledge stretching back to Newton and the scientific giants his work referenced.

Scientific publishing and referencing has become more formal since Newton’s time, with databases of citations allowing for sophisticated quantitative analyses of that flow of information between researchers.

The Institute for Scientific Information and the Web of Science Group provide a yearly snapshot of this flow, publishing a list of the researchers who are in the top 1 percent of their respective fields when it comes to the number of times their work has been cited.

Danielle Bassett, J. Peter Skirkanich Professor in the departments of Bioengineering and Electrical and Systems Engineering, and Jason Burdick, Robert D. Bent Professor in the department of Bioengineering, are among the 6,389 researchers named to the 2020 list.

Bassett is a pioneer in the field of network neuroscience, which incorporates elements of mathematics, physics,  biology and systems engineering to better understand how the overall shape of connections between individual neurons influences cognitive traits. Burdick is an expert in tissue engineering and the design of biomaterials for regenerative medicine; by precisely tailoring the microenvironment within these materials, they can influence stem cell differentiation or trigger the release of therapeutics.

Bassett and Burdick were named to the Web of Science’s 2019 Highly Cited Researchers list as well.

Originally posted in Penn Engineering Today.

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Using Lung-on-a-chip Technology to Find Treatments for Chlorine Gas Exposure

Huh’s organ-on-a-chip devices contain human cells, allowing for experiments that could not otherwise be practically or ethically performed.

Chlorine gas is a commonly used industrial chemical. It is also highly toxic and potentially deadly; it was used as a chemical weapon in both World War I and the Syrian Civil War and has led to multiple deaths from industrial accidents. Mixing certain household cleaners can also produce the toxic gas, leading to lasting lung injuries for which there are currently no effective treatments.

Now, researchers at Penn Engineering and Penn’s Perelman School of Medicine are collaborating with BARDA, the U.S. Office of Health and Human Services’ Biomedical Advanced Research and Development Authority, to address this need using their lung-on-a-chip technology.

The laboratory of Dan Huh, associate professor in the Department of Bioengineering, has developed a series of organ-on-a-chip platforms. These devices incorporate human cells into precisely engineered microfluidic channels that mimic an organ’s natural environment, providing a way to conduct experiments that would not otherwise be feasible.

Dan Huh
Dan Huh, PhD

Huh’s previous research has involved using a placenta-on-a-chip to study which drugs are able to reach a developing fetus; investigating microgravity’s effect on the immune system by sending one of his chips to the International Space Station; and testing treatments for dry eye disease using an eye-on-a-chip, complete with a mechanical blinking eyelid.

Read the full story on Penn Engineering Today. Media contact Evan Lerner.