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.
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.
We are thrilled to announce the appointment of Ning Jenny Jiang, Ph.D. as the tenured Peter & Geri Skirkanich Associate Professor of Innovation in the Department of Bioengineering at the University of Pennsylvania. Dr. Jenny Jiang comes to Penn from the Department of Biomedical Engineering at the University of Texas at Austin. She obtained her Ph.D. from Georgia Institute of Technology and did her postdoctoral training at Stanford University.
Jiang’s research focuses on systems immunology by developing technologies that enable high-throughput, high-content, single cell profiling of T cells in health and disease and she is recognized as one of the leading authorities in systems immunology and immunoengineering. She is a pioneer in developing tools in biophysics, genomics, immunology, and informatics and applying them to study systems immunology in human diseases. Her early work on the development of the first high-throughput immune-repertoire sequencing technology opened up a brand new field of immune-repertoire profiling. Her laboratory developed the first high-throughput in situ T cell receptor affinity measurement technology and she pioneered the development of integrated single T cell profiling technologies. These technological innovations have changed the paradigm of T cell profiling in disease diagnosis and in immune engineering for therapeutics. Using these technologies, her laboratory has made many discoveries in immunology, from unexpected infants’ immunity in malaria infection to “holes” in T cell repertoire in aging immune systems in elderly, from dysregulated T cells in HIV infection to high-throughput identification of neoantigen-specific T cell receptor for cancer immunotherapy.
Dr. Jiang was also recently elected to the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows for her outstanding contributions to the field of systems immunology and immunoengineering and devotion to the success of women in engineering. A virtual induction ceremony was held on March 26, 2021.
Additionally, Jiang is a recipient of numerous other awards, including the Damon Runyon-Rachleff Innovation Award, an NSF CAREER award, and a Chan Zuckerberg Initiative Neurodegeneration Challenge Network Ben Barres Early Career Acceleration Award. She was selected as one of National Academy of Medicine Emerging Leaders in Health and Medicine Scholars in 2019.
Jiang’s appointment will begin June 1, 2021. Welcome to Penn Bioengineering, Dr. Jiang!
N.B.: Edited 7/2/21 with full endowed chair title.
A National Institute of Allergy and Infectious Diseases lab freezer used for COVID-19 vaccine research. Both of the current mRNA-based COVID vaccines require ultra-cold freezers to prevent their mRNA from degrading, spurring research into other ways to stabilize the molecule.
As the technology behind two of the COVID-19 vaccines, Messenger RNA (mRNA) is having a moment. A single-stranded counterpart to DNA, mRNA translates its genetic code into proteins; by injecting mRNA engineered to produce proteins found on the exterior of the virus, the vaccine can train a person’s immune system to recognize the real thing without making them sick.
However, because mRNA is a relatively unstable molecule, distributing these vaccines involves extra logistical challenges. Doses must be transported and stored at ultra-cold temperatures to make sure the mRNA inside doesn’t degrade and lose the genetic information it carries.
Michael Mitchell
As mRNA vaccines and other therapies take off, researchers are looking for other ways to forestall this degradation. One of them is Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, who is studying the use of lipid nanoparticles to encapsulate and protect mRNA on its way into the cell. That sort of packaging would be particularly beneficial in proposed mRNA therapies for certain genetic disorders, which aim to deliver the correct protein-making instructions to specific organs, or even a fetus in utero.
But for stabilizing mRNA for vaccine distribution, many other strategies are being explored. In “Keeping covid vaccines cold isn’t easy. These ideas could help,” Wudan Yan of MIT Technology Review reached out to Mitchell for insight on LIONs, or lipid inorganic nanoparticles. These nanoparticles work the opposite way of Mitchell’s organic ones, with the mRNA stabilized by binding to their exteriors.
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 Moodyin Penn Medicine News.
The Lindback Awards, announced annually, are the most prestigious teaching awards that full-time faculty members at the University can receive.
Meaney is the Solomon R. Pollack Professor in Bioengineering and Senior Associate Dean of Penn Engineering and his research areas span from traumatic brain injury to brain network theory. He received his M.S. and Ph.D. in Bioengineering and Biomedical Engineering from Penn Engineering.
Speakers at the second annual Women in Data Science @ Penn Conference.
Last month, the second annual Women in Data Science (WiDS) @ Penn Conference virtually gathered nearly 500 registrants to participate in a week’s worth of academic and industry talks, live speaker Q&A sessions, and networking opportunities.
Hosted by Penn Engineering, Analytics at Wharton, Wharton Customer Analytics and Wharton’s Statistics Department, the conference’s theme — “This is What a Data Scientist Looks Like” – emphasized the depth, breadth, and diversity of data science, both in terms of the subjects the field covers and the people who enter it.
Following welcoming remarks from Erika James, Dean of the Wharton School, and Vijay Kumar, Nemirovsky Family Dean of Penn Engineering, the conference began with a keynote address from President of Microsoft US and Wharton alumna Kate Johnson.
Conference sessions continued throughout the week, featuring panels of academic data scientists from around Penn and beyond, industry leaders from IKEA Digital, Facebook and Poshmark, and lightning talks from students speakers who presented their data science research.
All of the conference’s sessions are now available on YouTube and the 2021 WiDS Conference Recap, including a talk titled “How Humans Build Models for the World” by Danielle Bassett, J. Peter Skirkanich Professor in Bioengineering and Electrical and Systems Engineering.
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.”
Manuela Teresa Raimondi was appointed Visiting Professor in Bioengineering in the Associated Faculty of the School of Engineering and Applied Science for the 2020-2021 academic year. Raimondi received her Ph.D. in Bioengineering in 2000 from Politecnico di Milano, Italy. She is currently a Full Professor of Bioengineering at Politecnico di Milano in the Department of Chemistry, Materials and Chemical Engineering “G. Natta”, where she teaches the course “Technologies for Regenerative Medicine” in the Biomedical Engineering graduate program.
Raimondi is the founder and Director of the Mechanobiology Lab and of the Interdepartmental Live Cell Imaging lab. She has pioneered the development of cutting edge tools for cell modelling, ranging from micro-engineered stem cell niches, to miniaturized windows for in vivo intravital imaging, to microfluidic culture systems to engineer tissue-equivalents and organoids for cell modelling and drug discovery. Her platforms are currently commercialized by her start-up, MOAB srl. Her research is funded by the European Research Council (ERC), by The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), by the European Commission, and by the European Space Agency.
“Getting to Penn was quite the challenge with the various travel restrictions and the pandemic, but I am used to overcoming adverse odds and I am really excited to be here now,” says Dr. Raimondi. “In this challenging time, when many new barriers are coming up, I think building bridges and new scientific collaborations is even more important. I very much look forward to being part of the Penn research community.”
Dr. Raimondi with host Riccardo Gottardi, PhD on Smith Walk
During her sabbatical at Penn, Raimondi is investigating her hypothesis that stem cells pluripotency reprogramming can be guided by mechanical cues. Over the past five years, she has cultured many different stem cell types in the “Nichoids,” the synthetic stem cell niche she developed, and gathered robust evidence on how physical constraints at the microscale level upregulate pluripotency. Raimondi is hosted in the Bioengineering and Biomaterials Lab of Riccardo Gottardi, Assistant Professor in Bioengineering and in Pediatrics at the Perelman School of Medicine, where she is helping to refine human stem cell sources that could be minimally manipulated for translational tissue engineering for a safe and effective use in regenerative therapies, as a key issue for clinical translation is the maintenance or enhancement of multipotency during cell expansion without exogenous agents or genetic modification.
“Dr. Raimondi is a trailblazer in Italy in regenerative medicine who has introduced many new concepts in a sometimes musty academic environment and has shattered a number of glass ceilings,” says Dr. Gottardi. “I think her sabbatical at Penn is a great opportunity for her and for the Penn community to build new and exciting trans-Atlantic collaborations.”
“Kevin Johnson is a gifted physician-scientist,” Gutmann said, “who has harnessed and aligned the power of medicine, engineering, and technology to improve the health of individuals and communities. He has championed the development and implementation of clinical information systems and artificial intelligence to drive medical research, encouraged the effective use of technology at the bedside, and empowered patients to use new tools to better understand how medications and supplements may affect their health. He is a board-certified pediatrician, and his commitment to patient health and welfare knows no age limits. In so many different settings, Kevin’s work is driving progress in patient care and improving our health care system. He is a perfect fit for Penn, where our goal is to create a maximally inclusive and integrated academic community to spur unprecedented global impact.”
Johnson is currently the Cornelius Vanderbilt Professor and chair of the Department of Biomedical Informatics at the Vanderbilt University School of Medicine, where he has taught since 2002. He is a world-renowned innovator in developing clinical information systems that improve best practices in patient safety and compliance with medical practice guidelines, especially the use of computer-based documentation systems and other digital technologies. His research bridges biomedical informatics, bioengineering, and computer science. As senior vice president for health information technology at the Vanderbilt University Medical Center from 2014 to 2019, he led the development of clinical systems that enabled doctors to make better treatment and care decisions for individual patients, in part by alerting patients as to how medications or supplements might affect their body chemistry, as well as new systems to integrate artificial intelligence into patient care workflows and to unify and simplify all the Medical Center’s clinical and administrative systems.
The author of more than 150 publications, books, or book chapters, Johnson has held numerous leadership positions in the American Medical Informatics Association and the American Academy of Pediatrics, 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 has been elected to the National Academy of Medicine (Institute of Medicine), American College of Medical Informatics, and Academic Pediatric Society and has received awards from the Robert Wood Johnson Foundation and American Academy of Pediatrics, among many others.
“Kevin Johnson exemplifies our most profound Penn values,” Pritchett said. “He is a brilliant innovator committed to bringing together disciplines across traditional boundaries. Yet he always does so in the service of helping others, finding technological solutions that can make a tangible impact on improving people’s lives. He will be an extraordinary colleague, teacher and mentor across multiple areas of our campus in the years to come.”
Johnson earned an M.D. from the Johns Hopkins University School of Medicine, an M.S. in medical informatics from Stanford University, and a B.S. with honors in biology from Dickinson College. He became the first Black chief resident in pediatrics at Johns Hopkins in 1992, and was a faculty member in both pediatrics and biomedical information sciences at Johns Hopkins until 2002.
The Penn Integrates Knowledge program was launched by Gutmann in 2005 as a University-wide initiative to recruit exceptional faculty members whose research and teaching exemplify the integration of knowledge across disciplines and who are appointed in at least two Schools at Penn.
We hope you will join us for the 2021 Grace Hopper Distinguished Lecture by Dr. Jennifer Lewis, presented by the Department of Bioengineering. For event links, email ksas@seas.upenn.edu.
Date: Thursday, March 25, 2021
Time: 3:00-4:00 PM EDT
Jennifer A. Lewis
Speaker: Jennifer A. Lewis, Sc.D.
Wyss Professor for Biologically Inspired Engineering
The Wyss Institue
Paulson School of Engineering and Applied Sciences
Harvard University
Title: “Biomanufacturing Vascularized Organoids and Functional Human Tissue”
Following the lecture, join us for a panel discussion “Horizon 2030: Engineering Life & Life in (Bio)Engineering” featuring Dr. Lewis and Penn faculty and moderated by Bioengineering students. Further details here.
Lecture Abstract:
Recent protocols in developmental biology are unlocking the potential for stem cells to undergo differentiation and self-assembly to form “mini-organs”, known as organoids. To bridge the gap from organoid building blocks (OBBs) to therapeutic functional tissues, integrative approaches that combine bottom-up organoid assembly with top-down bioprinting are needed. While it is difficult, if not impossible, to imagine how either organoids or bioprinting alone would fully replicate the complex multiscale features required for organ-specific function – their combination may provide an enabling foundation for de novo tissue manufacturing. My talk will begin by describing our recent efforts to generate organoids in vitro with perfusable microvascular networks that support their viability and maturation. Next, I will describe the generation of 3D vascularized organ-specific tissues by assembling OBBs into a living matrix that supports the embedded printing of macro-vessels by a process known as sacrificial writing in functional tissue (SWIFT). Though broadly applicable, I will highlight our recent work on kidney, cerebral, and cardiac tissue engineering.
Dr. Lewis Bio:
Jennifer A. Lewis is the Jianming Yu Professor of Arts and Sciences, the Wyss Professor for Biologically Inspired Engineering in the Paulson School of Engineering and Applied Sciences, and a core faculty member of the Wyss Institute at Harvard University. Her research focuses on 3D printing of functional, structural, and biological materials that emulate natural systems. Prior to joining Harvard, Lewis was a faculty member in the Materials Science and Engineering Department at the University of Illinois at Urbana-Champaign, where she served as the Director of the Materials Research Laboratory. Currently, she directs the Harvard Materials Research Science and Engineering Center (MRSEC) and serves the NSF Mathematical and Physical Sciences Advisory Committee.
Lewis has received numerous awards, including the Presidential Faculty Fellow Award, the American Chemical Society Langmuir Lecture Award, the Materials Research Society Medal Award, the American Ceramic Society Sosman and Roy Lecture Awards, and the Lush Science Prize. She is an elected member of the National Academy of Sciences, National Academy of Engineering, National Academy of Inventors, and the American Academy of Arts and Sciences. Her research has enjoyed broad coverage in the popular media. To date, she has co-founded two companies, Voxel8 Inc. and Electroninks, that are commercializing technology from her lab.
Information on the GraceHopper Lecture: In support of its educational mission of promoting the role of all engineers in society, the School of Engineering and Applied Science presents the GraceHopper Lecture Series. This series is intended to serve the dual purpose of recognizing successful women in engineering and of inspiring students to achieve at the highest level.
Rear Admiral GraceHopper was a mathematician, computer scientist, systems designer and the inventor of the compiler. Her outstanding contributions to computer science benefited academia, industry and the military. In 1928 she graduated from Vassar College with a B.A. in mathematics and physics and joined the Vassar faculty. While an instructor, she continued her studies in mathematics at Yale University where she earned an M.A. in 1930 and a Ph.D. in 1934. GraceHopper is known worldwide for her work with the first large-scale digital computer, the Navy’s Mark I. In 1949 she joined Philadelphia’s Eckert-Mauchly, founded by the builders of ENIAC, which was building UNIVAC I. Her work on compilers and on making machines understand ordinary language instructions lead ultimately to the development of the business language, COBOL. GraceHopper served on the faculty of the Moore School for 15 years, and in 1974 received an honorary degree from the University. In support of the accomplishments of women in engineering, each department within the School invites a prominent speaker for a one or two-day visit that incorporates a public lecture, various mini-talks and opportunities to interact with undergraduate and graduate students and faculty.
