Engineered White Blood Cells Eliminate Cancer

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“Macrophages killing cancer cell” photographed by Susan Arnold.

By silencing the molecular pathway that prevents macrophages from attacking our own cells, Penn Engineers have manipulated these white blood cells to eliminate solid tumors.

Cancer remains one of the leading causes of death in the U.S. at over 600,000 deaths per year. Cancers that form solid tumors such as in the breast, brain or skin are particularly hard to treat. Surgery is typically the first line of defense for patients fighting solid tumors. But surgery may not remove all cancerous cells, and leftover cells can mutate and spread throughout the body. A more targeted and wholistic treatment could replace the blunt approach of surgery with one that eliminates cancer from the inside using our own cells.

Dennis Discher, Robert D. Bent Professor in Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics, and postdoctoral fellow, Larry Dooling, provide a new approach in targeted therapies for solid tumor cancers in their study, published in Nature Biomedical Engineering. Their therapy not only eliminates cancerous cells, but teaches the immune system to recognize and kill them in the future.

“Due to a solid tumor’s physical properties, it is challenging to design molecules that can enter these masses,” says Discher. “Instead of creating a new molecule to do the job, we propose using cells that ‘eat’ invaders – macrophages.”

Macrophages, a type of white blood cell, immediately engulf and destroy – phagocytize – invaders such as bacteria, viruses, and even implants to remove them from the body. A macrophage’s innate immune response teaches our bodies to remember and attack invading cells in the future. This learned immunity is essential to creating a kind of cancer vaccine.

But, a macrophage can’t attack what it can’t see.

“Macrophages recognize cancer cells as part of the body, not invaders,” says Dooling. “To allow these white blood cells to see and attack cancer cells, we had to investigate the molecular pathway that controls cell-to-cell communication. Turning off this pathway – a checkpoint interaction between a protein called SIRPa on the macrophage and the CD47 protein found on all ‘self’ cells – was the key to creating this therapy.”

Read the full story in Penn Engineering Today.

Multiple members in the biophysical engineering lab lead by Dennis Discher, including co-lead author and postdoctoral fellow and Penn Bioengineering alumnus Jason Andrechak and Bioengineering Ph.D. student Brandon Hayes, contributed to this study. The research was funded by grants from the National Heart, Lung, and Blood Institute and the National Cancer Institute, including the Physical Sciences Oncology Network, of the US National Institutes of Health.

On a Different Wavelength, Nader Engheta Leads a Community in Light

Nader Engheta was puzzled when he got a call from the psychology department about a fish.
In the early 1990s, Engheta, a newly minted associate professor of electrical engineering in Penn’s School of Engineering and Applied Science, was a respected expert in radio wave technologies. But in recent years, his work had been expanding into subjects at once more eccentric and fundamental.

Nader Engheta was puzzled when he got a call from the psychology department about a fish.

In the early 1990s, Engheta, a newly minted associate professor of electrical engineering in Penn’s School of Engineering and Applied Science, was a respected expert in radio wave technologies. But in recent years, his work had been expanding into subjects at once more eccentric and fundamental.

Engheta’s interest in electromagnetic waves was not limited to radio frequencies, as a spate of fresh publications could attest. Some studies investigated a range of wave interactions with a class of matter known as a “chiral media,” materials with molecular configurations that exhibit qualities of left or right “handedness.” Others established practical electromagnetic applications for a bewildering branch of mathematics called “fractional calculus,” an area with the same Newtonian roots as calculus proper but a premise as eyebrow-raising as the suggestion a family might literally include two-and-a-half children.

Electromagnetic waves are organized on a spectrum of wavelengths. On the shorter end of the spectrum are high-energy waves, such as X-rays. In the middle, there is the limited range we see as visible light. And on the longer end are the lower-energy regimes of radio and heat.

Researchers tend to focus on one kind of wave or one section of the spectrum, exploring quirks and functions unique to each. But all waves, electromagnetic or not, share the same characteristics: They consist of a repeating pattern with a certain height (amplitude), rate of vibration (frequency), and distance between peaks (wavelength). These qualities can define a laser beam, a broadcasting voice, a wind-swept lake, or a violin string.

Engheta has never been the kind of scholar to limit the scope of his curiosity to a single field of research. He is interested in waves, and his fascination lies equally in the physics that determine wave behavior and the experimental technologies that push the boundaries of those laws.

So, when Edward Pugh, a mathematical psychologist studying the physiology of visual perception, explained that green sunfish might possess an evolutionary advantage for seeing underwater, Engheta listened.

Soon, the two Penn professors were pouring over microscope images of green sunfish retinas.

Read Devorah Fischler’s full story about Nader Engheta and watch an accompanying video at Penn Today.

Nader Engheta is H. Nedwill Ramsey Professor of Electrical and Systems Engineering at Penn Engineering, with secondary appointments in the departments of Bioengineering, Materials Science and Engineering, and Physics and Astronomy in the School of Arts & Sciences.

2023 Department of Bioengineering Juneteenth Address: “A White Neighbor, a Black Surgeon, and a Mormon Computer Scientist Walk into a Bar…” (Kevin B. Johnson)

Kevin B. Johnson, MD, MS

We hope you will join us for the 2023 Department of Bioengineering Juneteenth Address by Dr. Kevin B. Johnson.

Date: Wednesday, June 14, 2023
Start Time: 11:00 AM ET
Location: Berger Auditorium (Skirkanich Hall basement room 013)

Zoom link
Meeting ID: 925 0325 6013
Passcode: 801060

Following the event, a limited number of box lunches will be available for in-person attendees. If you would like a box lunch, please RSVP here by Monday, June 12 so we can get an accurate headcount.

Speaker: Kevin B. Johnson, MD, MS, FAAP, FAMIA, FACMI
David L. Cohen University Professor
Annenberg School for Communication, Bioengineering, Biostatistics, Epidemiology and Informatics, Computer and Information Science, Pediatrics
VP for Applied Informatics (UPHS), University of Pennsylvania

Title: “A White Neighbor, a Black Surgeon, and a Mormon Computer Scientist Walk into a Bar…”

Abstract: As we recognize Juneteenth, a holiday that brings awareness to what journalist Corey Mitchell calls “…a complex understanding of the nation’s past”, we also need to understand how many of our neighbors, staff, and faculty—even those born in the last 100 years—continue to navigate through the environment that made Juneteenth remarkable. Dr. Johnson will share a bit of his personal story and how this story informs his national service and passion for teaching.

Bio: Dr. Johnson is a leader of medical information technologies to improve patient care and safety. He is well regarded and widely known for pioneering discoveries in clinical informatics, leading to advances in data acquisition, medication management, and information aggregation in medical settings.

He is a board-certified pediatrician who has aligned the powers of medicine, engineering and technology to improve the health of individuals and communities. In work that bridges biomedical informatics, bioengineering and computer science, he has championed the development and implementation of clinical information systems and artificial intelligence to drive medical research. He has encouraged the effective use of technology at the bedside, and he has empowered patients to use new tools that help them to understand how medications and supplements may affect their health. He is interested in using advanced technologies such as smart devices and in developing computer-based documentation systems for the point of care. He also is an emerging champion of the use of digital media to enhance science communication, with a successful feature-length documentary describing health information exchange, a podcast (Informatics in the Round) and most recently, a children’s book series aimed at STEM education featuring scientists underrepresented in healthcare.

Dr. Johnson holds joint appointments in the Department of Computer and Information Science of the School of Engineering and Applied Science, and secondary appointments in Bioengineering and the Annenberg School for Communication. He serves as Vice President for Applied Informatics in the University of Pennsylvania Health System and as a Professor of Pediatrics at the Children’s Hospital of Philadelphia.

Before arriving at Penn, he served as the Cornelius Vanderbilt Professor and Chair of the Department of Biomedical Informatics at the Vanderbilt University School of Medicine, where he had taught since 2002. As Senior Vice President for Health Information Technology at the Vanderbilt University Medical Center, he led the development of clinical systems that enabled doctors to make better treatment and care decisions for individual patients, and introduced new systems to integrate artificial intelligence into patient care workflows.

The author of more than 150 publications, Dr. Johnson has held numerous leadership positions in the American Medical Informatics Association and the American Academy of Pediatrics. He leads the American Board of Pediatrics Informatics Advisory Committee, directs the Board of Scientific Counselors of the National Library of Medicine, and is a member of the NIH Council of Councils. He is an elected member of the National Academy of Medicine, American College of Medical Informatics and Academic Pediatric Society. He has received awards from the Robert Wood Johnson Foundation and American Academy of Pediatrics, among many others.

Penn Bioengineering Graduate Ella Atsavapranee Wins 2023 Fulbright Grant

Ella Atsavapranee (BE 2023)

Twenty-nine University of Pennsylvania students, recent graduates, and alumni have been offered Fulbright U.S. Student Program grants for the 2023-24 academic year, including eight seniors who graduated May 15.

They will conduct research, pursue graduate degrees, or teach English in Belgium, Brazil, Colombia, Denmark, Ecuador, Estonia, France, Germany, Guatemala, India, Israel, Latvia, Mexico, Nepal, New Zealand, the West Bank-Palestine territories, South Korea, Spain, Switzerland, Taiwan, and Thailand.

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.

Most of the Penn recipients applied for the Fulbright with support from the Center for Undergraduate Research and Fellowships.

Among the Penn Fulbright grant recipients for 2023-24 is Ella Atsavapranee, from Cabin John, Maryland, who graduated in May with a bachelor’s degree in bioengineering from the School of Engineering and Applied Science and a minor in chemistry from the College. She was offered a Fulbright to conduct research at the École Polytechnique Fédérale de Lausanne in Switzerland.

At Penn, Atsavapranee worked with Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor in Bioengineering, engineering lipid nanoparticles to deliver proteases that inhibit cancer cell proliferation. She has also worked with Shan Wang, Leland T. Edwards Professor in the School of Engineering and Professor of Electrical Engineering at Stanford University, using bioinformatics to discover blood biomarkers for cancer detection. To achieve more equitable health care, she worked with Lisa Shieh, Clinical Professor in Medicine at the Stanford School of Medicine,  to evaluate an AI model that predicts risk of hospital readmission and study how room placement affects patient experience.

Outside of research, Atsavapranee spread awareness of ethical issues in health care and technology as editor-in-chief of the Penn Bioethics Journal and a teaching assistant for Engineering Ethics (EAS 2030). She was also a Research Peer Advisor for the Penn Center for Undergraduate Research & Fellowships (CURF), a student ambassador for the Office of Admissions, and a volunteer for Service Link, Puentes de Salud, and the Hospital of the University of Pennsylvania. She plans to pursue a career as a physician-scientist to develop and translate technologies that are more affordable and accessible to underserved populations.

Read the full list of Penn Fulbright grant recipients for 2023-24 in Penn Today.

Folding@Home: How You, and Your Computer, Can Play Scientist

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Greg Bowman kneels, working on a server.
Folding@home is led by Gregory Bowman, a Penn Integrates Knowledge Professor who has appointments in the Departments of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science. (Image: Courtesy of Penn Medicine News)

Two heads are better than one. The ethos behind the scientific research project Folding@home is that same idea, multiplied: 50,000 computers are better than one.

Folding@home is a distributed computing project which is used to simulate protein folding, or how protein molecules assemble themselves into 3-D shapes. Research into protein folding allows scientists to better understand how these molecules function or malfunction inside the human body. Often, mutations in proteins influence the progression of many diseases like Alzheimer’s disease, cancer, and even COVID-19.

Penn is home to both the computer brains and human minds behind the Folding@home project which, with its network, forms the largest supercomputer in the world. All of that computing power continually works together to answer scientific questions such as what areas of specific protein implicated in Parkinson’s disease may be susceptible to medication or other treatment.

Led by Gregory Bowman, a Penn Integrates Knowledge professor of Biochemistry and Biophysics in the Perelman School of Medicine who has joint appointments in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science, Folding@home is open for any individual around the world to participate in and essentially volunteer their computer to join a huge network of computers and do research.

Using the network hub at Penn, Bowman and his team assign experiments to each individual computer which communicates with other computers and feeds info back to Philly. To date, the network is comprised of more than 50,000 computers spread across the world.

“What we do is like drawing a map,” said Bowman, explaining how the networked computers work together in a type of system that experts call Markov state models. “Each computer is like a driver visiting different places and reporting back info on those locations so we can get a sense of the landscape.”

Individuals can participate by signing up and then installing software to their standard personal desktop or laptop. Participants can direct the software to run in the background and limit it to a certain percentage of processing power or have the software run only when the computer is idle.

When the software is at work, it’s conducting unique experiments designed and assigned by Bowman and his team back at Penn. Users can play scientist and watch the results of simulations and monitor the data in real time, or they can simply let their computer do the work while they go about their lives.

Read the full story at Penn Medicine News.

Why is Machine Learning Trending in Medical Research but not in Our Doctor’s Offices?

by Melissa Pappas

Illustration of a robot in a white room with medical equipment.Machine learning (ML) programs computers to learn the way we do – through the continual assessment of data and identification of patterns based on past outcomes. ML can quickly pick out trends in big datasets, operate with little to no human interaction and improve its predictions over time. Due to these abilities, it is rapidly finding its way into medical research.

People with breast cancer may soon be diagnosed through ML faster than through a biopsy. Those suffering from depression might be able to predict mood changes through smart phone recordings of daily activities such as the time they wake up and amount of time they spend exercising. ML may also help paralyzed people regain autonomy using prosthetics controlled by patterns identified in brain scan data. ML research promises these and many other possibilities to help people lead healthier lives.

But while the number of ML studies grow, the actual use of it in doctors’ offices has not expanded much past simple functions such as converting voice to text for notetaking.

The limitations lie in medical research’s small sample sizes and unique datasets. This small data makes it hard for machines to identify meaningful patterns. The more data, the more accuracy in ML diagnoses and predictions. For many diagnostic uses, massive numbers of subjects in the thousands would be needed, but most studies use smaller numbers in the dozens of subjects.

But there are ways to find significant results from small datasets if you know how to manipulate the numbers. Running statistical tests over and over again with different subsets of your data can indicate significance in a dataset that in reality may be just random outliers.

This tactic, known as P-hacking or feature hacking in ML, leads to the creation of predictive models that are too limited to be useful in the real world. What looks good on paper doesn’t translate to a doctor’s ability to diagnose or treat us.

These statistical mistakes, oftentimes done unknowingly, can lead to dangerous conclusions.

To help scientists avoid these mistakes and push ML applications forward, Konrad Kording, Nathan Francis Mossell University 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, is leading an aspect of a large, NIH-funded program known as CENTER – Creating an Educational Nexus for Training in Experimental Rigor. Kording will lead Penn’s cohort by creating the Community for Rigor which will provide open-access resources on conducting sound science. Members of this inclusive scientific community will be able to engage with ML simulations and discussion-based courses.

“The reason for the lack of ML in real-world scenarios is due to statistical misuse rather than the limitations of the tool itself,” says Kording. “If a study publishes a claim that seems too good to be true, it usually is, and many times we can track that back to their use of statistics.”

Such studies that make their way into peer-reviewed journals contribute to misinformation and mistrust in science and are more common than one might expect.

Read the full story in Penn Engineering Today.

The Potential Futures of Neurotech

Roy Hoshi Hamilton, MD, MS, FAAN, FANA

Brain technology offers all kinds of exciting possibilities — from treating conditions like epilepsy or depression, to simply maximizing brain health. But medical ethicists are concerned about potential dangers and privacy concerns. Roy Hamilton, Professor of Neurology in the Perelman School of Medicine,  Director of the Penn Brain Science, Translation, Innovation, and Modulation (BrainSTIM) Center, and member of the Penn Bioengineering Graduate Group, spoke with WHYY about how brain stimulation is being used.

Listen to “Neurotech and the Growing Battle for Our Brains

Two from Penn Bioengineering Graduate Group Elected to the National Academy of Sciences

Four faculty from the University of Pennsylvania have been elected to the United States National Academy of Sciences (NAS). They are David Brainard of the School of Arts & Sciences; Duncan Watts of the Annenberg School of Communication, School of Engineering and Applied Science, and Wharton School; and Susan R. Weiss and Kenneth S. Zaret of the Perelman School of Medicine.

They join 120 members and 23 international members elected by their peers this year to NAS. Recognized for “distinguished and continuing achievements in original research,” this new class brings the total number of active members to 2,565 and of international members to 526.

Brainard and Zaret are members of the Penn Bioengineering Graduate Group.

David Brainard is the RRL Professor of Psychology, director of the Vision Research Center, and associate dean for the natural sciences in the School of Arts & Sciences. His research focuses on human vision, using both experiments and computer modeling of visual processing, to understand how the visual system deciphers information about objects from light entering the eye. Specifically, he and his lab are interested in color vision, conducting psychophysical experiments to investigate how the appearance of color is affected by an object’s surface properties and ambient light, and how color perception aids in identifying objects. Brainard is the recipient of many honors, including the Macbeth Award from the Inter-Society Color Council, Stein Innovation Award from Research to Prevent Blindness, and Edgard D. Tillyer Award from Optica. He is an elected member of the Society of Experimental Psychologists, a Silver Fellow of the Association for Research in Vision and Ophthalmology, and a Fellow of the Association for Psychological Science.

Kenneth Zaret

Kenneth S. Zaret is the Joseph Leidy Professor in the Department of Cell and Developmental Biology at the Perelman School of Medicine, director of the Institute for Regenerative Medicine, and a member of the Cell and Molecular Biology Graduate Program. His research focuses on gene regulation, cell differentiation, and chromatin structure, with a goal of elucidating these phenomena in the context of embryonic development and tissue regeneration. Pinpointing these aspects of development at the cellular level can serve as the basis for developing future therapeutics and experimental models that further scientists’ ability to understand and cure disease. Zaret has been the recipient of many honors, including a MERIT Award from the National Institutes of Health, the Stanley N. Cohen Biomedical Research Award, and election as a fellow of the American Association for the Advancement of Science.

Read the full announcement in Penn Today.

Michael Mitchell and Kyle Vining Win IDEA Prize from CiPD and Penn Health-Tech

Michael J. Mitchell
Kyle Vining

 Michael J. Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering, and Kyle Vining, Assistant Professor in Materials Science and Engineering and in Penn Dental Medicine and member of the Penn Bioengineering Graduate Group, have been awarded the second-annual IDEA (Innovation in Dental Medicine and Engineering to Advance Oral Health) Prize, issued by the Center for Innovation & Precision Dentistry (CiPD) and Penn Health-Tech.

“Through their collaborative research, they are aiming to develop next-generation treatments for dental caries (tooth-decay) using lipid nanoparticles, the same delivery vehicles employed in the mRNA COVID-19 vaccine technology.

‘This project shows the type of innovative ideas and collaborations that we are kickstarting through the IDEA prize,’ says Dr. Michel Koo, co-director of the CiPD and Professor at Penn Dental Medicine. ‘This is a great example of synergistic interaction at the interface of engineering and oral health’ adds Dr. Kate Stebe, co-director of the CiPD and Professor at Penn Engineering.”

Read the full announcement in Penn Dental Medicine News.

Franklin Medal Laureate Nader Engheta Honored at Sculpting Waves Symposium

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(Left to Right) Vijay Kumar, Nemirovsky Family Dean of Penn Engineering, Nader Engheta, H. Nedwill Ramsey Professor in Electrical and Systems Engineering, and Michele Marcolongo, Drosdick Endowed Dean of Villanova University’s College of Engineering

On April 26, scholars from all over the world gathered at Villanova University to celebrate extraordinary innovation in the physics and technology of light.

The Franklin Institute Awards Laureate Symposium honored Nader Engheta, H. Nedwill Ramsey Professor in Electrical and Systems Engineering, Bioengineering, Materials Science and Engineering in the School of Engineering and Applied Science and in Physics and Astronomy in the College of Arts & Sciences at the University of Pennsylvania . The event heralded the awards gala held on April 27, where Engheta received the Benjamin Franklin Medal in Electrical Engineering from the Franklin Institute in Philadelphia, Pennsylvania.

The symposium, titled “Sculpting Waves with Complex Materials,” explored the richness and breadth of Engheta’s impact.

In a glass-paneled lecture hall nestled between flowering dogwoods and limber pines, speakers attested to Engheta’s technical acumen and intellectual creativity, describing his pathbreaking work in light-matter interaction.

Andrea Alù, Distinguished Professor at the City University of New York, Einstein Professor of Physics at the Graduate Center, CUNY and former Penn Engineering postdoctoral fellow, cited Engheta as “one of the original pioneers of the field of complex electromagnetic structures and modern metamaterials,” and the “father” of four influential fields: analog computing with metamaterials, plasmonic cloaking, non-zero-index metamaterials and optical nanocircuits.

Read the full story in Penn Engineering Today.

Watch the recording of the 2023 Franklin Institute Awards Ceremony on the Institute’s Youtube page.