Carl June (center) is awarded the 2024 Breakthrough Prize in Life Sciences. His innovative contributions to CAR T cell therapy have transformed the approach to treating certain cancers. His co-recipient is Michel Sadelain of Sloan Kettering Memorial Hospital (right). Flanking them on the stage are (from left to right) Olivia Wilde, Camille Leahy, and Regina King. (Image: Courtesy of Breakthrough Prize)
In his acceptance speech for the 2024 Breakthrough Prize in Life Sciences, Carl June, a pioneer in cancer treatment, highlighted the people most affected by his groundbreaking work developing CAR T cell immunotherapy: the patients.
When all other cancer treatments failed them, said June, “instead of giving up, they pushed forward and volunteered for an unproven experimental new treatment. It’s because of these brave volunteers like our first patients Doug Olson, Bob Levis, and Emily Whitehead, that we have now treated over 34,000 cancer patients.”
June, the Richard W. Vague Professor in Immunotherapy in Penn’s Perelman School of Medicine and director of the Center for Cellular Immunotherapies (CCI) at Penn Medicine’s Abramson Cancer Center, was honored at the 10th Breakthrough Prize awards ceremony for the development of chimeric antigen receptor (CAR) T cell immunotherapy. This is a cancer treatment approach in which each patient’s T cells are modified to target and kill their cancer cells.
Held on Saturday, April 13, and nicknamed the “Oscars of Science,” world-renowned researchers exchanged lab coats for tuxedos at the star-studded Breakthrough Prize awards ceremony hosted by Emmy Award-winning actor and comedian James Corden. Actors Olivia Wilde and Regina King handed June and his co-winner, Michel Sadelain of Memorial Sloan Kettering Cancer Center, the awards.
“We’re so grateful to have some recognition for a lot of years of work on cancer research,” said June at the event. “I think the best thing is that people learn about this, that this came out of research right here in the country. Now there’s been 34,000 people treated and it just started 10 years ago so people need to understand the value of research to make these new breakthrough therapies.”
Patients being treated for B-cell non-Hodgkin’s Lymphoma (NHL) who are part of minority populations may not have equal access to cutting-edge CAR T cell therapies, according to a new analysis led by researchers from the Perelman School of Medicine and published in NEJM Evidence.
CAR T cell therapy is a personalized form of cancer therapy that was pioneered at Penn Medicine and has brought hope to thousands of patients who had otherwise run out of treatment options. Six different CAR T cell therapies have been approved since 2017 for a variety of blood cancers, including B-cell NHL that has relapsed or stopped responding to treatment. Image: iStock/PeopleImages
“CAR T cell therapy represents a major leap forward for blood cancer treatment, with many patients living longer than ever before, but its true promise can only be realized if every patient in need has access to these therapies,” says lead author Guido Ghilardi, a postdoctoral fellow in the laboratory of senior author Marco Ruella, an assistant professor of hematology-oncology and scientific director of the Lymphoma Program. “From the scientific perspective, we’re constantly working in the laboratory to make CAR T cell therapy work better, but we also want to make sure that when a groundbreaking treatment like this becomes available, it reaches all patients who might be able to benefit.”
Students test the GaitMate harness and structure as a tool to help recovering patients walk.
Penn students have been building their knowledge and hands-on experience in places all over the world through Penn Global Seminars. Last May, “Robotics and Rehabilitation” brought Penn students back to the tropical island of Jamaica to collaborate with local university students and make an impact on recovery and quality of life for patients in Kingston and beyond.
Course leaders Camillo Jose (CJ) Taylor, Raymond S. Markowitz President’s Distinguished Professor in Computer and Information Science (CIS), and Michelle J. Johnson, Associate Professor of Physical Medicine and Rehabilitation at the Perelman School of Medicine and Associate Professor in Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM) at Penn Engineering, brought the first cohort of students to the island in 2019.
“CJ and I are both Jamaicans by birth,” says Johnson. “We were both excited to introduce the next generation of engineers to robotics, rehabilitation and the process of culturally sensitive design in a location that we are personally connected to.”
As they built relationships with colleagues at the University of West Indies, Mona (UWI, Mona) and the University of Technology, Jamaica (UTECH), both Johnson and Taylor worked to tie the goals of the course to the location.
“In the initial iteration of the course, our goal was to focus on the applications of robotics to rehabilitation in a developing country where it is necessary to create solutions that are cost effective and will work in under-resourced settings,” says Taylor.
Taylor and Johnson wanted to make the course a regular offering, however, due to COVID-related travel restrictions, it wasn’t until last spring that they were able to bring it back. But when they did, they made up for lost time and expanded the scope of the course to include solving health problems for both people and the environment.
“While we started with a focus on people, we realized that the health and quality of life of a community is also impacted by the health of the environment,” says Taylor. “Jamaica has rich terrestrial and marine ecosystems, but those resources need to be monitored and regulated. We ventured into developing robotics tools to make environmental monitoring more effective and cost-friendly.”
One of those student-invented tools was a climate survey drone called “BioScout.”
“Our aim was to create a drone to monitor the ecosystem and wildlife in Jamaica,” says Rohan Mehta, junior in Systems Science and Engineering. “We wanted to help researchers and rangers who need to monitor wildlife and inspect forest sectors without entering and disturbing territories, but there were no available drones that met all of the following criteria necessary for the specific environment: affordable, modular, water-resistant and easy to repair. So we made our own.”
Another team of students created a smart buoy to reduce overfishing. The buoy was equipped with an alarm that goes off when fishermen get too close to a no-fishing zone.
Five other student teams dove into projects aligned to the original goals of the course. Their devices addressed patients’ decreased mobility due to diabetes, strokes and car accidents. These projects were sponsored by the Sir John Golding Rehabilitation Center.
One of which, the GaitMate, was engineered to help stroke patients who had lost partial muscle control regain their ability to walk.
“We developed a device that supports a patient’s weight and provides sensory feedback to help correct their form and gait as they walk on a treadmill, ultimately enhancing the recovery process and providing some autonomy to the patient,” says Taehwan Kim, senior in BE. “The device is also relatively cheap and simple, making it an option for a wide variety of physical therapy needs in Jamaica and other countries.”
Illustration of the 55LCC complex. (Image: Courtesy of Cameron Baines/Phospho Biomedical Animation)
When cells in the human body divide, they must first make accurate copies of their DNA. The DNA replication exercise is one of the most important processes in all living organisms and is fraught with risks of mutation, which can lead to cell death or cancer. Now, findings from biologists from the Perelman School of Medicine and from the University of Leeds have identified a multiprotein “machine” in cells that helps govern the pausing or stopping of DNA replication to ensure its smooth progress. Illustration of the 55LCC complex. (Image: Courtesy of Cameron Baines/Phospho Biomedical Animation)
The discovery, published in Cell, advances the understanding of DNA replication, helps explain a puzzling set of genetic diseases, and could inform the development of future treatments for neurologic and developmental disorders.
“We’ve found what appears to be a critical quality-control mechanism in cells,” says senior co-corresponding author Roger Greenberg, the J. Samuel Staub, M.D. Professor in the department of Cancer Biology, director of the Penn Center for Genome Integrity, and director of basic science at the Basser Center for BRCA at Penn Medicine. “Trillions of cells in our body divide every single day, and this requires accurate replication of our genomes. Our work describes a new mechanism that regulates protein stability in replicating DNA. We now know a bit more about an important step in this complex biological process.”
“The proposed studies lay the foundation to make a major scientific impact in the childhood leukemia field and ultimately improve outcomes for children,” says Vining.
A panel of expert and alumni judges chose 3 teams to advance to the School-wide, interdepartmental competition, to be held on May 3, 2024.
Team ADONA: Jude Barakat, Allison Elliott, Daniel Ghaderi, Aditi Ghalsasi, Taehwan Kim
ADONA (A Device for the Assisted Detection of Neonatal Asphyxia)
Hypoxic-ischemic encephalopathy (HIE) is a condition that arises from inadequate oxygen delivery or blood flow to the brain around the time of birth, resulting in long-term neurological damage. This birth complication is responsible for up to 23% of neonatal deaths worldwide. While effective treatments exist, current diagnostic methods require specialized neurologists to analyze an infant’s electroencephalography (EEG) signal, requiring significant time and labor. In areas where such resources and specialized training are even scarcer, the challenges are even more pronounced, leading to delayed or lack of treatment, and poorer patient outcomes. The Assisted Detection of Neonatal Asphyxia (ADONA) device is a non-invasive screening tool that streamlines the detection of HIE. ADONA is an EEG helmet that collects, wirelessly transmits, and automatically classifies EEG data using a proprietary machine learning algorithm in under two minutes. Our device is low-cost, automated, user-friendly, and maintains the accuracy and reliability of a trained neurologist. Our classification algorithm was trained using 1100 hours of annotated clinical data and achieved >85% specificity and >90% sensitivity on an independent 200 hour dataset. Our device is now produced in Agilus 30, a flexible and tear resistant material, that reduces form factor and ensures regulatory compliance. For our final prototype, we hope to improve electrode contact and integrate software with clinical requirements. Our hope is that ADONA will turn the promise of a safer birth into a reality, ensuring instant peace of mind and equitable access to healthcare, for every child and their families.
Team Epilog: Rohan Chhaya, Carly Flynn, Elena Grajales, Priya Shah, Dori Xu
Epilog
To address the critical need for effective, at-home seizure monitoring in pediatric neurology, particularly for Status Epilepticus (SE), our team developed Epilog: a rapid-application electroencephalography (EEG) headband. SE is a medical emergency characterized by prolonged or successive seizures and often presents with symptoms too subtle to notice or easily misinterpreted as post-convulsive fatigue. This leads to delayed treatment and increased risks of neurological damage and high mortality. Current seizure detection technologies are primarily based on motion or full-head EEG, rendering them ineffective at detecting SE and impractical for at-home use in emergency scenarios, respectively. Our device is designed to be applied rapidly during the comedown of a convulsive seizure, collect EEG data, and feed it into our custom machine learning algorithm. The algorithm processes this data in real-time and alerts caregivers if the child remains in SE, thereby facilitating immediate medical decision-making. Currently, Epilog maintains a specificity of 0.88 and sensitivity of 0.95, delivering decisions within 15 seconds post-seizure. We have demonstrated clean EEG signal acquisition from eight standard electrode placements and bluetooth data transmission from eight channels with minimal delay. Our headband incorporates all necessary electrodes and adjustable positioning of the electrodes for different head sizes. Our unique gel case facilitates rapid electrode gelation in less than 10 seconds. Our most immediate goals are validating our fully integrated device and improving features that allow for robust, long-term use of Epilog. Epilog promises not just data, but peace of mind, and empowering caregivers to make informed life-saving decisions.
Team NG-LOOP: Katherine Han, Jeffrey Huang, Dahin Song, Stephanie Yoon
NG-LOOP
Nasogastric (NG) tube dislodgement occurs when the feeding tube tip becomes significantly displaced from its intended position in the stomach, causing fatal consequences such as aspiration pneumonia. Compared to the 50% dislodgement rate in the general patient population, infant patients are particularly affected ( >60%) due to their miniature anatomy and tendency to unknowingly tug on uncomfortable tubes. Our solution, the Nasogastric Lightweight Observation and Oversight Product (NG-LOOP) provides comprehensive protection from NG tube dislodgement. Physical stabilization is combined with sensor feedback to detect and manage downstream complications of tube dislodgement. The lightweight external bridle, printed with biocompatible Accura 25 and coated with hydrocolloid dressing for comfort and grip, can prevent dislodgement 100% of the time given a tonic force of 200g. The sensor feedback system uses a DRV5055 linear hall effect sensor with a preset difference threshold, coupled with an SMS alert and smart plug inactivation of the feeding pump. A sensitivity of 90% and specificity of 100% in dislodgement detection was achieved under various conditions, with all feedback mechanisms being initiated in response to 100% of threshold triggers. Future steps involve integration with hospital-grade feeding pumps, improving the user interface, and incorporating more sizes for diverse age inclusivity.
Photos courtesy of Afraah Shamim, Coordinator of Educational Laboratories in the Penn BE Labs. View more photos on the Penn BE Labs Instagram.
Senior Design (BE 4950 & 4960) is a two-semester capstone course taught by David Meaney, Solomon R. Pollack Professor in Bioengineering and Senior Associate Dean of Penn Engineering, Erin Berlew, Research Scientist in the Department of Orthopaedic Surgery and Lecturer in Bioengineering, and Dayo Adewole, Postdoctoral Fellow of Otorhinolaryngology (Head and Neck Surgery) in the Perelman School of Medicine. Read more stories featuring Senior Design in the BE Blog.
Diagram of the optoPlateReader, a high-throughput, feedback-enabled optogenetics and spectroscopy device initially developed by Penn 2021 iGEM team.
For bioengineers today, light does more than illuminate microscopes. Stimulating cells with light waves, a field known as optogenetics, has opened new doors to understanding the molecular activity within cells, with potential applications in drug discovery and more.
Thanks to recent advances in optogenetic technology, much of which is cheap and open-source, more researchers than ever before can construct arrays capable of running multiple experiments at once, using different wavelengths of light. Computing languages like Python allow researchers to manipulate light sources and precisely control what happens in the many “wells” containing cells in a typical optogenetic experiment.
However, researchers have struggled to simultaneously gather data on all these experiments in real time. Collecting data manually comes with multiple disadvantages: transferring cells to a microscope may expose them to other, non-experimental sources of light. The time it takes to collect the data also makes it difficult to adjust metabolic conditions quickly and precisely in sample cells.
Now, a team of Penn Engineers has published a paper in Communications Biology, an open access journal in the Nature portfolio, outlining the first low-cost solution to this problem. The paper describes the development of optoPlateReader (or oPR), an open-source device that addresses the need for instrumentation to monitor optogenetic experiments in real time. The oPR could make possible features such as automated reading, writing and feedback in microwell plates for optogenetic experiments.
Left to right: Will Benman, Gloria Lee, Saachi Datta, Juliette Hooper, Grace Qian, David Gonzalez-Martinez, and Lukasz Bugaj (with Max).
The paper follows up on the award-winning work of six University of Pennsylvania alumni — Saachi Datta, M.D. Candidate at Stanford School of Medicine; Juliette Hooper, Programmer Analyst in Penn’s Perelman School of Medicine; Gabrielle Leavitt, M.D. Candidate at Temple University; Gloria Lee, graduate student at Oxford University; Grace Qian, Drug Excipient and Residual Analysis Research Co-op at GSK; and Lana Salloum, M.D. Candidate at Albert Einstein College of Medicine — who claimed multiple prizes at the 2021 International Genetically Engineered Machine Competition (iGEM) as Penn undergraduates.
The International Genetically Engineered Machine Competition (or iGEM) is the largest synthetic biology community and the premiere synthetic biology competition for both university and high school students from around the world. Hundreds of interdisciplinary teams of students compete annually, combining molecular biology techniques and engineering concepts to create novel biological systems and compete for prizes and awards through oral presentations and poster sessions.
The optoPlateReader was initially developed by Penn’s 2021 iGEM team, combining a light-stimulation device with a plate reader. At the iGEM competition, the invention took home Best Foundational Advance (best in track), Best Hardware (best from all undergraduate teams), and Best Presentation (best from all undergraduate teams), as well as a Gold Medal Distinction and inclusion in the Top 10 Overall and Top 10 Websites lists. (Read more about the 2021 iGEM team on the BE Blog.)
The original iGEM project focused on the design, construction, and testing of the hardware and software that make up the oPR, the focus of the new paper. After iGEM concluded, the team showed that the oPR could be used with real biological samples, such as cultures of bacteria. This work demonstrated that the oPR could be applied to real research questions, a necessary precursor to publication, and that the device could simultaneously monitor and manipulate living samples.
The main application for the oPR is in metabolic production (such as the creation of pharmaceuticals and bio-fuels). The oPR is able to issue commands to cells via light but can also take live readings about their current state. In the oPR, certain colors of light cause cells to carry out different tasks, and optical measurements give information on growth rates and protein production rates.
In this way, the new device is able to support production processes that can adapt in real time to what cells need, altering their behavior to maximize yield. For example, if an experiment produces a product that is toxic to cells, the oPR could instruct those cells to “turn on” only when the population of cells is dense and “turn off” when the concentration of that product becomes toxic and the cellular population needs to recover. This ability to pivot in real time could assist industries that rely on bioproduction.
The main challenges in developing this device were in incorporating the many light emitting diodes (LEDs) and sensors into a tiny space, as well as insulating the sensors from the nearby LEDs to ensure that the measured light came from the sample and not from the instrument itself. The team also had to create software that could coordinate the function of nearly 100 different sets of LEDs and sensors. Going forward, the team hopes to spread the word about the open-source oPR to other researchers studying metabolic production to enable more efficient research.
Lukasz Bugaj, Assistant Professor in Bioengineering and senior author of the paper, served as the team’s mentor along with Brian Chow, formerly an Associate Professor in Bioengineering and a founding member of the iGEM program at MIT, and Jose Avalos, Associate Professor of Chemical and Biological Engineering at Princeton University.
Key to the project’s development was the guidance of Bioengineering graduate students Will Benman, David Gonzalez Martinez, and Gabrielle Ho, as well as that of Saurabh Malani, a graduate student at Princeton University.
Visualization of a CAR T cell (in red) attacking a cancer cell (in blue) (Meletios Varras via Getty Images)
For patients with certain types of cancer, CAR T cell therapy has been nothing short of life changing. Developed in part by Carl June, Richard W. Vague Professor at Penn Medicine, and approved by the Food and Drug Administration (FDA) in 2017, CAR T cell therapy mobilizes patients’ own immune systems to fight lymphoma and leukemia, among other cancers.
However, the process for manufacturing CAR T cells themselves is time-consuming and costly, requiring multiple steps across days. The state of the art involves extracting patients’ T cells, then activating them with tiny magnetic beads, before giving the T cells genetic instructions to make chimeric antigen receptors (CARs), the specialized receptors that help T cells eliminate cancer cells.
Now, Penn Engineers have developed a novel method for manufacturing CAR T cells, one that takes just 24 hours and requires only one step, thanks to the use of lipid nanoparticles (LNPs), the potent delivery vehicles that played a critical role in the Moderna and Pfizer-BioNTech COVID-19 vaccines.
In a new paper in Advanced Materials, Michael J. Mitchell, Associate Professor in Bioengineering, describes the creation of “activating lipid nanoparticles” (aLNPs), which can activate T cells and deliver the genetic instructions for CARs in a single step, greatly simplifying the CAR T cell manufacturing process. “We wanted to combine these two extremely promising areas of research,” says Ann Metzloff, a doctoral student in Bioengineering and NSF Graduate Research Fellow in the Mitchell lab and the paper’s lead author. “How could we apply lipid nanoparticles to CAR T cell therapy?”
Georgia Georgostathi accepts the Wolf-Hallac Award from Dean Vijay Kumar.
Each spring, awards are given to undergraduate students in the School of Engineering and Applied Science in recognition of outstanding scholarly achievements and service to the School and University community. The 2024 award recipients were recognized in a ceremony held on Wednesday, March 27, 2024 at the Penn Museum.
Read the full list of Bioengineering undergraduate award winners below.
The Wolf-Hallac Award: Georgia Georgostathi. This award was established in October 2000 to recognize the graduating female senior from across Penn Engineering’s departments who is seen as a role model, has achieved a high GPA (in the top 10% of their class), and who has demonstrated a commitment to school and/or community.
Alexandra Dumas accepts the Maddie Magee Award for Undergraduate Excellence.
The Maddie Magee Award for Undergraduate Excellence: Alexandra Dumas. This award is given to a Penn Engineering senior who best exemplifies the energy, enthusiasm, and excellence of Penn Engineering alumna Madison “Maddie” N. Magee (MEAM BS ’21, BE MS ’21).
The Hugo Otto Wolf Memorial Prize: Jude Barakat & Dori Xu. This prize is awarded to one or more members of each department’s senior class, distinguishing students who meet with great approval of the professors at large through “thoroughness and originality” in their work.
The Herman P. Schwan Award: Angela Song. This department award honors a graduating senior who demonstrates the “highest standards of scholarship and academic achievement.”
Penn Engineering Exceptional Service Awards recognize students for their outstanding service to the University and their larger communities: Srish Chenna, Daniel Ghaderi, Taehwan Kim and Daphne Nie.
Chaitanya Karimanasseri accepts the Bioengineering Student Leadership Award.
The Bioengineering Student Leadership Award: Chaitanya Karimanasseri. This award is given annually to a student in Bioengineering who has demonstrated, through a combination of academic performance, service, leadership, and personal qualities, that they will be a credit to the Department, the School, and the University.
Additionally, the Bioengineering Department also presents a single lab group with the Albert Giandomenico Award which reflects their “teamwork, leadership, creativity, and knowledge applied to discovery-based learning in the laboratory.” This year’s group consists of Alexandra Dumas, Georgia Georgostathi, Daphne Nie and Angela Song.
A full list of Penn Engineering award descriptions and recipients can be found here.
BE award winners enjoy the ceremony reception in the Penn Museum.
LeAnn Dourte, Practice Associate Professor in Bioengineering, has been one of the most active members of the Penn Engineering faculty in pioneering the Structured, Active, In-Class Learning (SAIL) model of education. In a recent issue of the Penn Almanac, Dourte boils down her practical advice for faculty looking to make their courses more interactive and dynamic into one simple philosophy: “Just change 10 minutes.”
“The effectiveness of these 10-minute activities hinges on their alignment with learning objectives. Students are always on the lookout for anything that they see as busy-work, so articulating the purpose of such activities is paramount to their success. These are some of the goals I think about when I design activities with my learning objectives in mind. While some of these approaches are specific to subjects with quantitative problem solving, many have applications across disciplines.”
Dourte’s article articulates her active learning approach, along with a list of specific learning objectives, including encouraging diverse perspectives, promoting error recognition and correction, and more.
