Myeloma cells producing monoclonal proteins of varying types, created by Scientific Animations under the Creative Commons Attributions-Share Alike International 4.0 License
Multiple myeloma is an incurable bone marrow cancer that kills over 100,000 people every year. Known for its quick and deadly spread, this disease is one of the most challenging to address. As these cancer cells move through different parts of the body, they mutate, outpacing possible treatments. People diagnosed with severe multiple myeloma that is resistant to chemotherapy typically survive for only three to six months. Innovative therapies are desperately needed to prevent the spread of this disease and provide a fighting chance for those who suffer from it.
Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering (BE), and Christian Figueroa-Espada, doctoral student in BE at the University of Pennsylvania School of Engineering and Applied Science, created an RNA nanoparticle therapy that makes it impossible for multiple myeloma to move and mutate. The treatment, described in their study published in PNAS, turns off a cancer-attracting function in blood vessels, disabling the pathways through which multiple myeloma cells travel.
By shutting down this “chemical GPS” that induces the migration of cancer cells, the team’s therapy stops the spread of multiple myeloma, helping to eliminate it altogether.
“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.”
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.
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.
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 Journaland 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.
Neil Sheppard, Adjunct Associate Professor of Pathology and Laboratory Medicine in the Perelman School of Medicine, and David Mai, a Bioengineering graduate student in the School of Engineering and Applied Science, explained the findings of their recent study, which offered a potential strategy to improve T cell therapy in solid tumors, to the European biotech news website Labiotech.
Bella Mirro (left) poses with Penn President Liz Magill. (Image: Prestige Portraits)
For 150 years, Ivy Day has been an annual tradition at Penn, with each graduating class installing at least one new plaque and planting a sprig of ivy. On Saturday, May 13, the class of 2023 added to the 200-plus plaques throughout campus with a stone designed by Marah Sanchez, a Class of 2023 student in the School of Nursing, and remarks from Vice Provost for University Life Karu Kozuma.
“The Ivy Day Award Ceremony is a special celebration that gives us an opportunity to acknowledge the contributions and accomplishments of our graduating student leaders,” Kozuma says. “It is also an occasion to create connections. At the ceremony, we have the privilege of meeting family members and loved ones who have supported the students, while the students can connect with alumni who received the same recognition 25 years ago.”
Among the honorees were several Penn Bioengineering students.
Isabella Mirro was presented with the Penn Student Agencies Award by President Liz Magill. This award recognizes distinguished academic achievement and significant leadership in undergraduate activities by a member of the senior class. Mirro, a graduate of the undergraduate Class of 2023, was recently profiled in 34th Street Magazine.
President Liz Magill (right) with the winners of the President’s Innovation Prize. (Image: Prestige Portraits)
Additionally, Tifara Boyce, Gabriela Cano, Gabriella Daltoso, Sophie Ishiwari, and Caroline Magro were formally presented with the President’s Innovation Prize for their startup Sonura. Sonura was featured in Penn Today for their award-winning beanie for NICU infants.
Read the full list of Ivy Day awards in Penn Today.
Matthew Aronson and Alexandra Dumas are both members of the lab of Riccardo Gottardi, Assistant Professor in Pediatrics in the Perelman School of Medicine and in Bioengineering in the School of Engineering and Applied Science. Both presented their work at the recent 2023 SFB Annual Meeting and Exposition in San Diego, California in April 2023 and were honored with STAR Awards for their research.
The Gottardi Bioengineering and Biomaterials Laboratory studies treatment and function restoration for children with otolaryngologic disorders through the Children’s Hospital of Philadelphia (CHOP) in the Division of Otolaryngology.
Matthew Aronson
MatthewAronson is a third-year Ph.D. student in Bioengineering, an Ashton Fellow, and a NSF Fellow. His doctoral research focuses on studying pediatric airway diseases and disorders. More specifically, he is interested in how bacteria of the upper airway are responsible for the development and progression the disease subglottic stenosis, narrowing of the airway. In addition to understanding this devastating disease in the context of pediatric patients at CHOP, he also designed a novel drug-eluting endotracheal tube to deliver a selective antimicrobial peptide to function as a treatment modality for the prevention of the disease.
Alexandra Dumas
Alexandra Dumas is a rising fourth-year undergraduate in Bioengineering from Durban, South Africa. She is a PURM Fellow and a University Scholar. Her recent work in the Gottardi Lab focuses on using decellularized cartilage scaffolds to repair the meniscus and airway. After her undergraduate degree, she hopes to pursue a Ph.D. or M.D.-Ph.D. in bioengineering to pursue the design of new biomaterials for low-resource communities.
Read more stories featuring Gottardi and his team here.
Recipients of the 2023 President’s Innovation Prize, team Sonura, five bioengineering graduates from the School of Engineering and Applied Science, have created a device that filters out disruptive environmental noises for infants in neonatal intensive care units. Their beanie offers protection and fosters parental connection to newborns while also supporting their development.
Machines beeping and whirring in a rhythmic chorus, the droning hum of medical equipment, and the bustles of busy health care providers are the familiar sounds of an extended stay at a hospital. This cacophony can create a sense of urgency for medical professionals as they move about with focused determination, closely monitoring their patients, but for infants in neonatal intensive care units (NICU) this constant noise can be overwhelming and developmentally detrimental.
Enter Tifara Boyce, from New York City; Gabriela Cano, from Lawrenceville, New Jersey; Gabriella Daltoso, from Boise, Idaho; Sophie Ishiwari, from Chicago, and Caroline Magro, from Alexandria, Virginia, bioengineering graduates from the School of Engineering and Applied Science, who have created the Sonura Beanie. Their device filters out harmful noises for NICU infants while supporting cognitive and socioemotional development by allowing parents to send voice messages to their newborns.
The Sonura team members are recipients of the 2023 President’s Innovation Prize, which includes an award of $100,000 and an additional $50,000 living stipend per team member. The recent graduates will spend the year developing their product.
“The Penn engineers behind Sonura are determined to make a difference in the world,” says President Liz Magill. “They identified a substantial medical challenge that affects many parents and their newborn children. With the guidance of their mentors, they are taking key steps to address it and in doing so are improving the developmental prospects for children in the NICU. I am proud the University is able to support their important work.”
Prototype of the Sonura Beanie. (Image: Courtesy of the Sonura team)
She was particularly struck by the noisiness of the environment and considered the neurodevelopmental outcomes that may arise following long-term exposure to the harsh sounds at a critical developmental stage for infants. This concern prompted Magro to consult her team about potential solutions.
“I was really eager to tackle this problem because it bears some personal significance to me,” says Cano, who works on the device’s mobile application. “My sister was a NICU baby who was two months premature, so, when Caroline and I started talking about the issues a disruptive environment could cause, it seemed like the pieces of a puzzle started to come together.”
Each year, Penn Engineering’s seniors present their Senior Design projects, a year-long effort that challenges them to test and develop solutions to real-world problems, to their individual departments. The top three projects from each department go on to compete in the annual Senior Design Competition, sponsored by the Engineering Alumni Society, which involves pitching projects to a panel of judges who evaluate their potential in the market.
We are proud that two of the four awards went to Penn Bioengineering teams!
This year’s panel included over forty judges, and each winning team received a $2,000 prize, generously sponsored by Penn Engineering alumnus Kerry Wisnosky.
Congratulations to all of the 2023 participants and winners!
Technology & Innovation Award
This award recognized the team whose project represents the highest and best use of technology and innovation to leverage engineering principles.
Winner: Team BAMBI Department: Bioengineering Team Members: Ria Dawar, Pallavi Jonnalagadda, Jessica Ling, Grace Qian Mentor: Erin Anderson Instructors: Erin Berlew, Sevile Mannickarottu, and David Meaney Abstract: BAMBI (Biointelligent Apnea Monitor for Bradycardia-Prone Infants) is a tripartite system that leverages machine learning and automated mechanical stimulation to detect and treat apnea of prematurity in the NICU.
Judges’ Choice Award
This award recognizes the group whose all-around presentation captures the best of the senior design program’s different facets: ideation, scope of project, team problem-solving, execution and presentation.
Winner: Team StablEyes Department: Bioengineering Team Members: Ella Atsavapranee, Jake Becker, Ruoming Fan, Savan Patel Mentor: Erin Anderson, Dr. Drew Scoles and Dr. Tomas Aleman (Children’s Hospital of Philadelphia, Penn Medicine) Instructors: Erin Berlew, Sevile Mannickarottu, and David Meaney Abstract: StablEyes consists of a stabilization mount that provides fine, motorized control of the handheld OCT to improve ease of use for physicians and machine learning-based software to aid in diagnosis from retinal images.
Read the full list of SEAS Senior Design Competition Award winners in Penn Engineering Today.
Read more about all the Class of 2023 Penn Bioengineering Senior Design Teams in the Penn BE Labs website.
The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year, the Department of Bioengineering at the University of Pennsylvania recognizes the stellar work of four graduate students in Bioengineering.
Margaret Billingsley
Dissertation: “Ionizable Lipid Nanoparticles for mRNA CAR T Cell Engineering”
Maggie Billingsley
Margaret earned a bachelor’s degree in Biomedical Engineering from the University of Delaware where she conducted research in the Day Lab on the use of antibody-coated gold nanoparticles for the detection of circulating tumor cells. She conducted doctoral research in the lab of Michael J. Mitchell, J. and Peter Skirkanich Assistant Professor in Bioengineering. After defending her thesis at Penn in 2022, Margaret began postdoctoral training at the Massachusetts Institute of Technology (MIT) in the Hammond Lab where she is investigating the design and application of polymeric nanoparticles for combination therapies in ovarian cancer. She plans to use these experiences to continue a research career focused on drug delivery systems.
“Maggie was an absolutely prolific Ph.D. student in my lab, who pioneered the development of new mRNA lipid nanoparticle technology to engineer the immune system to target and kill tumor cells,” says Mitchell. “Maggie is incredibly well deserving of this honor, and I am so excited to see what she accomplishes next as a Postdoctoral Fellow at MIT and ultimately as a professor running her own independent laboratory at a top academic institution.”
Victoria Muir
Dissertation: “Designing Hyaluronic Acid Granular Hydrogels for Biomaterials Applications”
Victoria Muir
Victoria is currently a Princeton University Presidential Postdoctoral Research Fellow in the lab of Sujit S. Datta, where she studies microbial community behavior in 3D environments. She obtained her Ph.D. in 2022 as an NSF Graduate Research Fellow at Penn Bioengineering under the advisement of Jason A. Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. She received a B.ChE. in Chemical Engineering from the University of Delaware in 2018 as a Eugene DuPont Scholar. Outside of research, Victoria is highly active in volunteer and leadership roles within the American Institute of Chemical Engineers (AIChE), currently serving as Past Chair of the Young Professionals Community and a member of the Career and Education Operating Council (CEOC). Victoria’s career aspiration is to become a professor of chemical engineering and to lead a research program at the interaction of biomaterials, soft matter, and microbiology.
“Victoria was a fantastic Ph.D. student,” says Burdick. “She worked on important projects related to granular materials from the fundamentals to applications in tissue repair. She was also a leader in outreach activities, a great mentor to numerous undergraduates, and is already interviewing towards an independent academic position.”
Sadhana Ravikumar
Dissertation: “Characterizing Medial Temporal Lobe Neurodegeneration Due to Tau Pathology in Alzheimer’s Disease Using Postmortem Imaging”
Sadhana Ravikumar
Sadhana completed her B.S. in Electrical Engineering at the University of Cape Town, South Africa in 2014 and her M.S. in Biomedical Engineering from Carnegie Mellon University in 2017. Outside of the lab, she enjoys spending time in nature and exploring restaurants in Philadelphia with friends. She focused her doctoral work on the development of computational image analysis techniques applied to ex vivo human brain imaging data in the Penn Image Computing and Science Laboratory of Paul Yushkevich, Professor of Radiology at the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group. She hopes to continue working at the intersection of machine learning and biomedical imaging to advance personalized healthcare and drug development.
“Dr. Sadhana Ravikumar’s Ph.D. work is a tour de force that combines novel methodological contributions crafted to address the challenge of anatomical variability in ultra-high resolution ex vivo human brain MRI with new clinical knowledge on the contributions of molecular pathology to neurodegeneration in Alzheimer’s disease,” says Yushkevich. “I am thrilled that this excellent contribution, as well as Sadhana’s professionalism and commitment to mentorship, have been recognized through the Sol Pollack award.”
Hannah Zlotnick
Dissertation: “Remote Force Guided Assembly of Complex Orthopaedic Tissues”
Hannah Zlotnick
Hannah was a Ph.D. candidate in the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and in Bioengineering. She successfully defended her thesis and graduated in August 2022. During her Ph.D., Hannah advanced the state-of-the-art in articular cartilage repair by harnessing remote fields, such as magnetism and gravity. Using these non-invasive forces, she was able to control cell positioning within engineered tissues, similar to the cell patterns within native cartilage, and enhance the integration between cartilage and bone. Her work could be used in many tissue engineering applications to recreate complex tissues and tissue interfaces. Hannah earned a B.S. in Biological Engineering from the Massachusetts Institute of Technology (MIT) in 2017 during which time she was also a member of the women’s varsity soccer team. At Penn, Hannah was also involved in the Graduate Association of Bioengineers (GABE) intramurals & leadership, and helped jumpstart the McKay DEI committee. Since completing her Ph.D., Hannah has begun her postdoctoral research as a Schmidt Science Fellow in Jason Burdick’s lab at the University of Colorado Boulder where she looks to improve in vitro disease models for osteoarthritis.
“Hannah was an outstanding graduate student, embodying all that is amazing about Penn BE – smart, driven, inventive and outstanding in every way,” says Mauck. “ I can’t wait to see where she goes and what she accomplishes!”
Congratulations to our four amazing 2023 Sol Pollack Award winners!
At a special luncheon on campus, President Liz Magill recognized this year’s eight awardees, who she said ‘exemplify imagination, creativity, grit, and leadership.’
President Liz Magill and Interim President Beth Winkelstein with the 2023 PEP and PIP awardees.
When Kenneth Pham got the call last week, he said he was “shocked.”
“It’s kind of embarrassing, the president’s call went straight to voicemail,” the fourth-year chemistry major said. “But I called her office right back.”
Pham quickly learned that he and Catherine Chang had earned one of this year’s President’s Engagement Prizes (PEP) for their project Act First, which, once established, will provide critical first-aid training to high school students in Philadelphia. Both members of Penn’s Medical Emergency Response Team since their earliest years on campus, Pham, from South Philadelphia, and Chang, from Taiwan, hope to extend the program’s lifesaving education off campus, teaching others how to reverse opioid overdoses, successfully administer CPR, and prevent life-threatening bleeding.
“We feel honored to be recognized for the work we’ve been so passionate about, and we are so glad to finally have the opportunity to work on this,” Pham said Wednesday afternoon, sitting next to Chang as well as his parents at a celebratory luncheon for this year’s PEP, as well as President’s Innovation Prize (PIP), winners.
“After all our hard work this past year, it feels great,” added Chang, who graduated with her degree in biology in December.
President Magill meets with Sonura teammate Sophie Ishiwari and her startup’s mentor Brian Halak, from Penn Engineering.
In addition to Act First, fourth-year neuroscience major Lucy Lee has been awarded a PEP for her initiative Communities for Childbirth, and fourth-year bioengineering majors Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce have received a PIP for their startup Sonura. All three projects will be awarded $100,000 for implementation expenses, as well as a $50,000 living stipend per team member to be used in the coming year, immediately following graduation.
“This is a uniquely Penn experience,” said President Liz Magill, speaking to the awardees and their family members and mentors at the gathering. “No other university has a program quite like this, and I would like to say that’s in part because no other university has the student body we have at Penn, so focused on creating solutions to pressing societal problems. That particular characteristic is a trait that we celebrate, coming down from—yes, you guessed it—our founder Ben Franklin.”
This award recognizes the group whose all-around presentation captures the best of the senior design program’s different facets: ideation, scope of project, team problem-solving, execution and presentation.
