“Educating the Next Generation of Civically Engaged Technologists”

Brit Shields, Ph.D.

Brit Shields, Senior Lecturer in Bioengineering, has brought her expertise in the history and sociology of science to her leading role in developing and improving the ethics curriculum for all students in the School of Engineering and Applied Science. Most recently, this includes adapting the core ethics engineering ethics course “Technological Innovation and Civil Discourse in a Dynamic World” (EAS 204) for the Stavros Niarchos Foundation (SNF) Paideia Program. SNF Paideia courses, open to all Penn undergraduates, “integrate students’ personal, professional, and civic development […] focus[ing] on dialogue, wellness, service, and citizenship from different disciplinary and interdisciplinary perspectives.” A recent SNF Paideia blog post goes into detail about the changes made by Shields and co-instructor Christopher Yoo, John H. Chestnut Professor of Law, Communication, and Computer and Information Science, to suit the SNF Paideia Program, including its “explicit focus on civil discourse and technology.” According to Shields:

“I really wanted to break down the false dichotomy between technological expertise or humanities training for the students and open up the opportunity for Engineering students to consider themselves to have an important role, not just creating technological systems but also being important participants in civil discourse.”

Michelle Johnson, Ph.D.

The course also includes guest lectures by Penn faculty, including Michelle Johnson, Associate Professor in Bioengineering and Physical Medicine and Rehabilitation, and students learn to analyze how guest lecturers communicate their research to the public, for example, in the case of Johnson, in the form of a TED Talk and scholarly articles: “Through her TedTalk, journal articles and visit to the class, Michelle Johnson demonstrates how researchers are attuned to the specific preferences of the rehabilitative robots they are creating for patients…engaged scholarship at its finest.”

Read “Educating the Next Generation of Civically Engaged Technologists” in SNF Paideia Perspectives.

“Science vs Science: The Contradictory Fight Over Whether Electromagnetic Hypersensitivity is Real”

cell phones
Kenneth R. Foster, Ph.D.

Electromagnetic fields are everywhere, and especially so in recent years. To most of us, those fields are undetectable. But a small number of people believe they have an actual allergy to electromagnetic fields. Ken Foster, a Professor Emeritus of Bioengineering, has heard these arguments before.  “Activists would point to all these biological effects studies and say, ‘There must be some hazard’; health agencies would have meticulous reviews of literature and not see much of a problem.”

Listen to the episode of The Pulse and read the full story at WHYY.

Originally posted on Penn Today.

Bioengineering’s Organ-on-a-chip Spin-off is Growing

Andrei Georgescu (left) and Dan Huh are the co-founders of Vivodyne, a spin-off of Huh’s BIOLines lab.

Dan Huh, Associate Professor in the Department of Bioengineering, has been steadily growing a collection of organs-on-chips. 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.

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.

Now, he and his colleagues are taking this technology out of their lab and into industry with their company, Vivodyne.

Andrei Georgescu, Huh’s lab-member and co-founder of Vivodyne, recently spoke with Technical.ly Philly’s Paige Gross about the growth of their company.

Research into potential drugs is usually performed first on mice, and success is only found in a fraction of humans once implemented in clinical trials, Andrei Georgescu, cofounder and CEO of Vivodyne, told Technical.ly. The genetic makeup just isn’t similar enough. But technology that allows scientists to test therapies on lab-grown human organs called “organs on chip” is allowing for testing without human subjects.

The organs on chip allow for a drug to react to tissue in a more similar way to the body than it would in a petri dish, Georgescu said. Cells sense their environment very well, he added.

“We’re making the environment more complicated, making its spacial features complicated enough to match the native complexity of the organs,” he said. “When [cells] sense a softer environment, they start to behave more realistically. Their response to the drug is more realistic.”

Continue reading “This Penn-founded biotech company specializing in human ‘organs on chip’ raised $4M” at Technical.ly Philly. 

Originally posted in Penn Engineering Today.

Modified Nanoparticles Can Stop Osteoarthritis Development

Zhiliang Cheng

As we age, the cushioning cartilage between our joints begins to wear down, making it harder and more painful to move. Known as osteoathritis, this extremely common condition has no known cure; if the symptoms can’t be managed, the affected joints must be surgically replaced.

Now, researchers are exploring whether their specially designed nanoparticles can deliver a new inflammation inhibitor to joints, targeting a previously overlooked enzyme called sPLA2.

Zhiliang Cheng, a research associate professor in the Department of Bioengineering, recently collaborated with members of Penn Medicine’s McKay Orthopaedic Research Laboratory, on a study of this approach, published in the journal Science Advances.

The normal function of sPLA2 is to provide lipids (fats) that promote a variety of inflammation processes. The enzyme is always present in cartilage tissue, but typically in low levels. However, when the researchers examined mouse and human cartilage taken from those with osteoarthritis, disproportionately high levels of the enzyme were discovered within the tissue’s structure and cells.

“This marked increase strongly suggests that sPLA2 plays a role in the development of osteoarthritis,” said the study’s corresponding author, Zhiliang Cheng, PhD, a research associate professor of Bioengineering. “Being able to demonstrate this showed that we were on the right track for what could be a potent target for the disease.”

The next step was for the study team – which included lead author Yulong Wei, MD, a researcher in Penn Medicine’s McKay Orthopaedic Research Laboratory – to put together a nanoparticle loaded with an sPLA2 inhibitor. This would block the activity of sPLA2 enzyme and, they believed, inflammation. These nanoparticles were mixed with animal knee cartilage in a lab, then observed as they diffused deeply into the dense cartilage tissue. As time progressed, the team saw that the nanoparticles stayed there and did not degrade significantly or disappear. This was important for the type of treatment the team envisioned.

Continue reading at Penn Medicine News.

Originally posted in Penn Engineering Today.

“New Biosealant Can Stabilize Cartilage, Promote Healing After Injury”

New research from Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and Bioengineering and Director of Penn Medicine’s McKay Orthopaedic Research Laboratory, announces a “new biosealant therapy may help to stabilize injuries that cause cartilage to break down, paving the way for a future fix or – even better – begin working right away with new cells to enhance healing.” Their research was published in Advanced Healthcare Materials. The study’s lead author was Jay Patel, a former postdoctoral fellow in the McKay Lab and now Assistant Professor at Emory University and was contributed to by Claudia Loebel, a postdoctoral research in the Burdick lab and who will begin an appointment as Assistant Professor at the University of Michigan in Fall 2021. In addition, the technology detailed in this publication is at the heart of a new company (Forsagen LLC) spun out of Penn with support from the Penn Center for Innovation (PCI) Ventures Program, which will attempt to spearhead the system’s entry into the clinic. It is co-founded by both Mauck and Patel, along with study co-author Jason Burdick, Professor in Bioengineering, and Ana Peredo, a PhD student in Bioengineering.

Read the story in Penn Medicine News.

Bioengineering Contributes to “New COVID-19 Testing Technology at Penn”

César de la Fuente, Ph.D., a Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, is leading a team to develop an electrode that can be easily printed at low cost to provide COVID-19 test results from your smart phone.

A recent Penn Medicine blog post surveys the efforts across Penn and the Perelman School of Medicine to develop novel says to detect SARS-CoV-2 and features several Department of Bioengineering faculty and Graduate Group members, including César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering; Arupa Ganguly, Professor in Genetics; A.T. Charlie Johnson, Rebecca W. Bushnell Professor in Physics and Astronomy; Lyle Ungar, Professor in Computer and Information Science; and Ping Wang, Associate Professor in Pathology and Laboratory Medicine.

Read “We’ll Need More than Vaccines to Vanquish the Virus: New COVID-19 Testing Technology at Penn” by Melissa Moody in Penn Medicine News.

Penn, CHOP and Yale Researchers’ Molecular Simulations Uncover How Kinase Mutations Lead to Cancer Progression

by Evan Lerner

A computer model of a mutated anaplastic lymphoma kinase (ALK), a known oncogenic driver in pediatric neuroblastoma.

Kinases are a class of enzymes that are responsible for transferring the main chemical energy source used by the body’s cells. As such, they play important roles in diverse cellular processes, including signaling, differentiation, proliferation and metabolism. But since they are so ubiquitous, mutated versions of kinases are frequently found in cancers. Many cancer treatments involve targeting these mutant kinases with specific inhibitors.

Understanding the exact genetic mutations that lead to these aberrant kinases can therefore be critical in predicting the progression of a given patient’s cancer and tailoring the appropriate response.

To achieve this understanding on a more fundamental level, a team of researchers from the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine, the Children’s Hospital of Philadelphia (CHOP) and researchers at the Yale School of Medicine’s Cancer Biology Institute, have constructed molecular simulations of a mutant kinase implicated in pediatric neuroblastoma, a childhood cancer impacting the central nervous system.

Using their computational model to study the relationship between single-point changes in the kinase’s underlying gene and the altered structure of the protein it ultimately produces, the researchers revealed useful commonalities in the mutations that result in tumor formation and growth. Their findings suggest that such computational approaches could outperform existing profiling methods for other cancers and lead to more personalized treatments.

The study, published in the Proceedings of the National Academy of Sciences, was led by Ravi Radhakrishnan, Professor and chair of Penn Engineering’s Department of Bioengineering and professor in its Department of Chemical and Biomolecular Engineering, and Mark A. Lemmon, Professor of Pharmacology at Yale and co-director of Yale’s Cancer Biology Institute. The study’s first authors were Keshav Patil, a graduate student in Penn Engineering’s Department of Chemical and Biomolecular Engineering, along with Earl Joseph Jordan and Jin H. Park, then members of the Graduate Group in Biochemistry and Molecular Biology in Penn’s Perelman School of Medicine. Krishna Suresh, an undergraduate student in Radhakrishnan’s lab, Courtney M. Smith, a graduate student in Lemmon’s lab, and Abigail A. Lemmon, an undergraduate in Lemmon’s lab, contributed to the study. They collaborated with Yaël P. Mossé, Associate Professor of Pediatrics at Penn Medicine and in the division of oncology at CHOP.

“Some cancers rely on the aberrant activation of a single gene product for tumor initiation and progression,” says Radhakrishnan. “This unique mutational signature may hold the key to understanding which patients suffer from aggressive forms of the disease or for whom a given therapeutic drug may yield short- or long-term benefits. Yet, outside of a few commonly occurring ‘hotspot’ mutations, experimental studies of clinically observed mutations are not commonly pursued.”

Read the full post in Penn Engineering Today.

BE Seminar: “Deciphering the Dynamics of the Unconscious Brain Under General Anesthesia” (Emery Brown)

Emery Brown, MD, PhD

Speaker: Emery N. Brown, MD, PhD
Edward Hood Taplin Professor of Medical Engineering and of Computational Neuroscience, MIT
Warren M. Zapol Professor of Anaesthesia, Harvard Medical School
Massachusetts General Hospital

Date: Thursday, April 1, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Deciphering the Dynamics of the Unconscious Brain Under General Anesthesia”

Abstract:

General anesthesia is a drug induced state that is critical for safely and humanely allowing a patient to undergo surgery or an invasive diagnostic procedure. During the last 10 years the study of the neuroscience of anesthetic drugs has been an active area of research. In this lecture we show how anesthetics create altered states of arousal by creating oscillation that impede how the various parts of the brain communicate. These oscillations, which are readily visible on the electroencephalogram (EEG), change systematically with anesthetic dose, anesthetic class and patient age. We will show how the EEG oscillations can be used to monitor the brain states of patients receiving general anesthesia, manage anesthetic delivery and learn about fundamental brain physiology.

EMERY BROWN BIO:

Emery N. Brown is the Edward Hood Taplin Professor of Medical Engineering and Professor of Computational Neuroscience at Massachusetts Institute of Technology. He is the Warren M. Zapol Professor of Anaesthesia at Harvard Medical School and Massachusetts General Hospital (MGH), and an anesthesiologist at MGH.

Dr. Brown received his BA (magna cum laude) in Applied Mathematics from Harvard College, his MA and PhD in statistics from Harvard University, and his MD (magna cum laude) from Harvard Medical School. He completed his internship in internal medicine at the Brigham and Women’s Hospital and his residency in anesthesiology at MGH. He joined the staff at MGH, the faculty at Harvard Medical School in 1992 and the faculty at MIT in 2005.

Dr. Brown is an anesthesiologist-statistician recognized for developing signal processing algorithms for neuroscience data analysis and for defining the neurophysiological mechanisms of general anesthesia.

Dr. Brown was a member of the NIH BRAIN Initiative Working Group. He is a fellow of the IEEE, the AAAS, the American Academy of Arts and Sciences and the National Academy of Inventors. Dr. Brown is a member of the National Academy of Medicine, the National Academy of Sciences and the National Academy of Engineering. He received an NIH Director’s Pioneer Award, the National Institute of Statistical Sciences Sacks Award, the American Society of Anesthesiologists Excellence in Research Award, the Dickson Prize in Science, the Swartz Prize for Theoretical and Computational Neuroscience and a Doctor of Science (honoris causa) from the University of Southern California.

Watch the Inaugural Joseph Bordogna Forum Lecture by Dr. John Brooks Slaughter

The inaugural Joseph Bordogna Forum took place on Wednesday, February 24 and featured a talk from John Brooks Slaughter, Deans’ Professor of Education and Engineering at USC’s Viterbi School of Engineering and Rossier School of Education, entitled a “Call to Action for Racial Justice and Equity in Engineering.”

Dr. Slaughter was joined by panelists Jennifer R. Lukes, Professor in Mechanical Engineering and Applied Mechanics, Oladayo Adewole, an alumnus in Robotics who recently defended his doctoral dissertation in Bioengineering, and CJ Taylor, Raymond S. Markowitz President’s Distinguished Professor in Computer and Information Science and Associate Dean, Diversity, Equity and Inclusion, who moderated the talk.

Dr. Slaughter talked about how microaggressions can often be a barrier to student success and emphasized on the importance of mentorship for underrepresented minorities: “If faculty members seek to improve the retention of underrepresented minorities, often times more has to be done than introducing science and math principles early on in their education, but instead, the unique backgrounds of these students must be understood.”

Originally posted in Penn Engineering Today.

‘RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases?’

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

As COVID-19 vaccines roll out, the concept of using mRNA to fend off viruses has become a part of the public dialogue. However, scientists have been researching how mRNA can be used to in life-saving medical treatments well before the pandemic.

The “m” in “mRNA” is for “messenger.” A single-stranded counterpart to DNA, it translates the genetic code into the production of proteins, the building blocks of life. The Moderna and Pfizer COVID-19 vaccines work by introducing mRNA sequences that act as a set of instructions for the body to produce proteins that mimic parts of the virus itself. This prepares the body’s immune response to recognize the real virus and fight it off.

Because it can spur the production of proteins that the body can’t make on its own, mRNA therapies also have the potential to slow or prevent genetic diseases that develop before birth, such as cystic fibrosis and sickle-cell anemia.

However, because mRNA is a relatively unstable molecule that degrades quickly, it needs to be packaged in a way that maintains its integrity as its delivered to the cells of a developing fetus.

To solve this challenge, Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, is researching the use of lipid nanoparticles as packages that transport mRNA into the cell. He and William H. Peranteau, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at Children’s Hospital of Philadelphia, recently co-authored a “proof-of-concept” paper investigating this technique.

In this study, published in Science Advances, Mitchel examined which nanoparticles were optimal in the transport of mRNA to fetal mice. Although no disease or organ was targeted in this study, the ability to administer mRNA to a mouse while still in the womb was demonstrated, and the results are promising for the next stages of targeted disease prevention in humans.

Mitchel spoke with Tom Avril at The Philadelphia Inquirer about the mouse study and its implications for treatment of rare infant diseases through the use of mRNA, ‘the messenger of life.’

Penn bioengineering professor Michael J. Mitchell, the other senior author of the mouse study, tested various combinations of lipids to see which would work best.

The appeal of the fatty substances is that they are biocompatible. In the vaccines, for example, two of the four lipids used to make the delivery spheres are identical to lipids found in the membranes of human cells — including plain old cholesterol.

When injected, the spheres, called nanoparticles, are engulfed by the person’s cells and then deposit their cargo, the RNA molecules, inside. The cells respond by making the proteins, just as they make proteins by following the instructions in the person’s own RNA. (Important reminder: The RNA in the vaccines cannot become part of your DNA.)

Among the different lipid combinations that Mitchell and his lab members tested, some were better at delivering their cargo to specific organs, such as the liver and lungs, meaning they could be a good vehicle for treating disease in those tissues.

Continue reading Tom Avril’s ‘RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases?’ at The Philadelphia Inquirer.