Jenny Jiang, the Peter & Geri Skirkanich Associate Professor of Innovation in the department of Bioengineering, has received a Lloyd J. Old STAR Program grant from the Cancer Research Institute (CRI), which is a major supporter of cancer immunotherapy research and clinical trials with the goal of curing all types of cancer.
The CRI Lloyd J. Old Scientists Taking Risks (STAR) Program “provides long-term funding to mid-career scientists, giving them the freedom and flexibility to pursue high-risk, high-reward research at the forefront of discovery and innovation in cancer immunotherapy.” This prestigious grant was give to six awardees this year, chosen from a pool of hundreds of applicants, and recognizes “future leaders in the field of cancer immunotherapy [who are expected to] carry out transformational research.”
The Old STAR Program Grant comes with $1.25 million in funding over 5 years to support the awardees’ cancer immunology research.
Jiang, who recently joined Penn Bioengineering, is a pioneer in developing tools in genomics, biophysics, immunology, and informatics and applying them to study systems immunology and immune engineering in human diseases. She was also inducted into the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows in March 2021 for her outstanding contributions to the field of systems immunology and immunoengineering and devotion to the success of women in engineering. 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.
“The STAR Award from CRI allows my lab to answer some of the fundamental questions in T cell biology, such as is the T cell repertoire complete to cover all possible cancer antigens, as well as to improve the efficacy of T cell based cancer immunotherapies,” says Jiang.
Understanding how the brain works is a major research challenge, with many theories and models developed to explain how complex information is processed and represented. One area of particular interest is vision, a major component of neural activity. In humans, for example, there is evidence that around half of the neurons in the cortex are related to vision.
Researchers are eager to understand how the visual cortex can process and retain information about objects in motion in a way that allows people to take in dynamic scenes while still retaining information about and recognizing the objects around them.
“One of the biggest challenges of all the sensory systems is to maintain a consistent representation of our surroundings, despite the constant changes taking place around us. The same holds true for the visual system,” says Davide Zoccolan, director of SISSA’s Visual Neuroscience Laboratory. “Just look around us: objects, animals, people, all on the move. We ourselves are moving. This triggers rapid fluctuations in the signals acquired by the retina, and until now it was unclear whether the same type of variations apply to the deeper layers of the visual cortex, where information is integrated and processed. If this was the case, we would live in tremendous confusion.”
Experiments using static stimuli, such as photographs, have found that information from the sensory periphery are processed in the visual cortex according to a finely tuned hierarchy. Deeper regions of the brain then translate this information about visual scenes into more complex shapes, objects, and concepts. But how this process works in more dynamic, real-world settings is not well understood.
To shed light on this, the researchers analyzed neural activity patterns in multiple visual cortical areas in rodents while they were being shown dynamic visual stimuli. “We used three distinct datasets: one from SISSA, one from a group in KU Leuven led by Hans Op de Beeck and one from the Allen Institute for Brain Science in Seattle,” says Zoccolan. “The visual stimuli used in each were of different types. In SISSA, we created dedicated video clips showing objects moving at different speeds. The other datasets were acquired using various kinds of clips, including from films.”
Next, the researchers analyzed the signals registered in different areas of the visual cortex through a combination of sophisticated algorithms and models developed by Penn’s Eugenio Pasini and Vijay Balasubramanian. To do this, the researchers developed a theoretical framework to help connect the images in the movies to the activity of specific neurons in order to determine how neural signals evolve over different time scales.
“The art in this science was figuring out an analysis method to show that the processing of visual images is getting slower as you go deeper and deeper in the brain,” says Balasubramanian. “Different levels of the brain process information over different time scales; some things could be more stable, some quicker. It’s very hard to tell if the time scales across the brain are changing, so our contribution was to devise a method for doing this.”
The retiring CIS professor chats about his recent ACM SIGGRAPH election and his expansive computer graphics path.
Norman Badler’selection into the 2021 ACM SIGGRAPH Academy Class is right on time. After nearly five decades of teaching and trailblazing in the Penn community, the Rachleff Family Professor in the Department of Computer and Information Sciences retired at the end of the spring semester.
When he arrived at the University in 1974, CIS itself was only about 2 years old, and there was virtually no computer graphics focus or program at all. Badler had no intention to teach it.
“At that time, I was actually a computer vision researcher, but I was also working a little bit in natural language,” says Badler. “So I was literally brought in to fit between the chair, Aravind Joshi, who was a natural language person, and the computer vision person. It wasn’t until about three or four years after I came here that I switched over to computer graphics. Mostly because there was a vacuum and a need and an excitement.”
Several years after completing his dissertation in computer vision and forming a career path to head in that direction, Badler “started getting serious about computer graphics.” An organization that was getting its start around the same time as his Penn career would play a major role: ACM SIGGRAPH (the Association for Computing Machinery’s Special Interest Group on Computer Graphics and Interactive Techniques).
With the goal of supporting partnerships between minority-serving educational institutions and leading materials science research centers, NSF’s Partnership for Research & Education in Materials (PREM) program funds innovative research programs and provides institutional support to increase recruitment, retention, and graduation by underrepresented groups as well as providing underserved communities access to materials research and education.
‘Research at the frontier’
With this PREM award, known as the Advancing Device Innovation through Inclusive Research and Education (ADIIR) program, researchers from Penn and UPR’s Humacao and Cayey campuses will conduct research on the properties of novel carbon-based materials with unique properties, and will study the effects of surface modification in new classes of sensors, detectors, and purification devices.
Thanks to this collaboration of more than 20 years, both institutions have made significant scientific and educational progress aided by biannual symposia and regular pre-pandemic travel between both institutions before the pandemic, resulting in a rich portfolio of publications, conference presentations, patents, students trained, and outreach programs.
“Together we have been publishing good papers that have impact, and we’ve really cultivated a culture of collaboration and friendship between our institutions,” says Penn’s Arjun Yodh, former director of the LRSM. “Our goal is to carry out research at the frontier and, in the process, nurture promising students from Puerto Rico and Penn.”
Ivan Dmochowski, a chemistry professor at Penn who has been involved with PREM for several years, says that this program has helped his group connect with experts in Puerto Rico whose skills complement his group’s interests in protein engineering. Dmochowski has also hosted UPR faculty members and students in his lab and also travelled to Puerto Rico before the pandemic to participate in research symposia, seminars, and outreach events.
“I’ve had students who have benefitted from being a co-author on a paper or having a chance to mentor students, and the faculty we’ve interacted with are exceptional,” Dmochowski says. “There’s a lot of benefit for both me and my students, and I’ve enjoyed our interactions both personally and scientifically.”
Penn’s Daeyeon Lee, a chemical and biomolecular engineering professor who has been involved with PREM for several years, regularly hosts students and faculty from UPR while working on nanocarbon-based composite films for sensor applications. The success of this collaboration relies on unique materials made by researchers at UPR combined with a method for processing them into composite structures developed in Lee’s lab.
“What I really admire about people at PREM, both faculty and students, is their passion,” says Lee. “I think that’s had a really positive impact on my students and postdocs who got to interact with them because they got to see the passion that the students brought.”
Susan Margulies, Professor Emeritus in Bioengineering, has been selected to lead the National Science Foundation’s (NSF) Directorate of Engineering, “the first biomedical engineer to head the directorate.” Margulies is chair of the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University. She earned her master’s and doctoral degrees from Penn Bioengineering before joining the department as an Assistant Professor in 1993.
In a press release from Emory University, Margulies stated that, “The opportunity to serve the NSF resonates with my values — catalyzing impact through innovation, rigor, partnership, and inclusion.” The announcement continues:
“Building on initiatives she developed at the University of Pennsylvania, Margulies prioritized career development for faculty and Ph.D. graduates during her years leading Coulter BME. She added dedicated staff to help doctoral students prepare for increasingly popular career paths outside of academia. The department increased the diversity of Ph.D. students and improved faculty diversity at all ranks during her tenure. Margulies oversaw hiring of 20 new faculty members and launched formalized mentoring for early career professors, including creating a new associate chair position dedicated to faculty development.”
Margulies will step down from her position as chair in Coulter BME though she will remain in the Georgia Tech and Emory faculty. Her Injury Biomechanics Lab studies “the influence of mechanical factors on the structure and function of human tissues from the macroscopic to microscopic level, with an emphasis on the brain and lungs.”
The COVID vaccines currently being deployed were developed with unprecedented speed, but the mRNA technology at work in some of them is an equally impressive success story. Because any desired mRNA sequence can be synthesized in massive quantities, one of the biggest hurdles in a variety of mRNA therapies is the ability to package those sequences into the lipid nanoparticles that deliver them into cells.
Now, thanks to manufacturing technology developed by bioengineers and medical researchers at the University of Pennsylvania, a hundred-fold increase in current microfluidic production rates may soon be possible.
The researchers’ advance stems from their design of a proof-of-concept microfluidic device containing 128 mixing channels working in parallel. The channels mix a precise amount of lipid and mRNA, essentially crafting individual lipid nanoparticles on a miniaturized assembly line.
This increased speed may not be the only benefit; more precisely controlling the nanoparticles’ size could make treatments more effective. The researchers tested the lipid nanoparticles produced by their device in a mouse study, showing they could deliver therapeutic RNA sequences with four-to-five times greater activity than those made by conventional methods.
The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, and David Issadore, Associate Professor in Penn Engineering’s Department of Bioengineering, along with Sarah Shepherd, a doctoral student in both of their labs. Rakan El-Mayta, a research engineer in Mitchell’s lab, and Sagar Yadavali, a postdoctoral researcher in Issadore’s lab, also contributed to the study.
They collaborated with several researchers at Penn’s Perelman School of Medicine: postdoctoral researcher Mohamad-Gabriel Alameh, Lili Wang, Research Associate Professor of Medicine, James M. Wilson, Rose H. Weiss Orphan Disease Center Director’s Professor in the Department of Medicine, Claude Warzecha, a senior research investigator in Wilson’s lab, and Drew Weissman, Professor of Medicine and one of the original developers of the technology behind mRNA vaccines.
“We believe that this microfluidic technology has the potential to not only play a key role in the formulation of current COVID vaccines,” says Mitchell, “but also to potentially address the immense need ahead of us as mRNA technology expands into additional classes of therapeutics.”
Studying drug effects on human muscles just got easier thanks to a new “muscle-on-a-chip,” developed by a team of researchers from Penn’s School of Engineering and Applied Science and Inha University in Incheon, Korea.
Muscle tissue is essential to almost all of the body’s organs, however, diseases such as cancer and diabetes can cause muscle tissue degradation or “wasting,” severely decreasing organ function and quality of life. Traditional drug testing for treatment and prevention of muscle wasting is limited through animal studies, which do not capture the complexity of the human physiology, and human clinical trials, which are too time consuming to help current patients.
An “organ-on-a-chip” approach can solve these problems. By growing real human cells within microfabricated devices, an organ-on-a-chip provides a way for scientists to study replicas of human organs outside of the body.
Using their new muscle-on-a-chip, the researchers can safely run muscle injury experiments on human tissue, test targeted cancer drugs and supplements, and determine the best preventative treatment for muscle wasting.
This research was published in Science Advances and was led by Dan Huh, Associate Professor in the Department of Bioengineering, and Mark Mondrinos, then a postdoctoral researcher in Huh’s lab and currently an Assistant Professor of Biomedical Engineering at Tulane University. Their co-authors included Cassidy Blundell and Jeongyun Seo, former Ph.D. students in the Huh lab, Alex Yi and Matthew Osborn, then research technicians in the Huh lab, and Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Professor in the Department of Materials Science and Engineering. Lab members Farid Alisafaei and Hossein Ahmadzadeh also contributed to the research. The team collaborated with Insu Lee and professors Sun Min Kim and Tae-Joon Jeon of Inha University.
In order to conduct meaningful drug testing with their devices, the research team needed to ensure that cultured structures within the muscle-on-a-chip were as close to the real human tissue as possible. Critically, they needed to capture muscle’s “anisotropic,” or directionally aligned, shape.
“In the human body, muscle cells adhere to specific anchor points due to their location next to ligament tissue, bones or other muscle tissue,” Huh says. “What’s interesting is that this physical constraint at the boundary of the tissue is what sculpts the shape of muscle. During embryonic development, muscle cells pull at these anchors and stretch in the spaces in between, similar to a tent being held up by its poles and anchored down by the stakes. As a result, the muscle tissue extends linearly and aligns between the anchoring points, acquiring its characteristic shape.”
The team mimicked this design using a microfabricated chip that enabled similar anchoring of human muscle cells, sculpting three-dimensional tissue constructs that resembled real human skeletal muscle.
A.T. Charlie Johnson, Rebecca W. Bushnell Professor of Physics and Astronomy at the Penn School of Arts & Sciences, and member of the Penn Bioengineering Graduate Group has been working with a team of researchers on a new “electronic nose” that could help track the spread of COVID-19 based on the disease’s unique odor profile. Now, similar research shows that vapors emanating from blood samples can be tested to distinguish between benign and cancerous pancreatic and ovarian cells. Johnson presented the results at the annual American Society of Clinical Oncology meeting on June 4 (Abstract # 5544):
“It’s an early study but the results are very promising,” Johnson said. “The data shows we can identify these tumors at both advanced and the earliest stages, which is exciting. If developed appropriately for the clinical setting, this could potentially be a test that’s done on a standard blood draw that may be part of your annual physical.”
The National Science Foundation’s CAREER Award is given to early-career researchers in order to kickstart their careers in innovative and pivotal research while giving back to the community in the form of outreach and education. Alex Hughes, Assistant Professor in Bioengineering and in Cell and Developmental Biology, is among the Penn Engineering faculty members who have received the CAREER Award this year.
Hughes plans to use the funds to develop a human kidney model to better understand how the development of cells and tissues influences congenital diseases of the kidney and urinary tract.
The model, known as an “organoid,” is a lab-grown piece of human kidney tissue on the scale of millimeters to centimeters, grown from cultured human cells.
“We want to create a human organoid structure that has nephrons, the filters of the kidney, that are properly ‘plumbed’ or connected to the ureteric epithelium, the tubules that direct urine towards the bladder,” says Hughes. “To achieve that, we have to first understand how to guide the formation of the ureteric tubule networks, and then stimulate early nephrons to fuse with those networks. In the end, the structures will look like ‘kidney subunits’ that could potentially be injected and fused to existing kidneys.”
The field of bioengineering has touched on questions similar to those posed by Hughes, focusing on drug testing and disease treatment. Some of these questions can be answered with the “organ-on-a-chip” approach, while others need an even more realistic model of the organ. The fundamentals of kidney development and questions such as “how does the development of nephrons affect congenital kidney and urinary tract anomalies?” require an organoid in an environment as similar to the human body as possible.
“We decided to start with the kidney for a few reasons,” says Hughes. “First, because its development is a beautiful process; the tubule growth is similar to that of a tree, splitting into branches. It’s a complex yet understudied organ that hosts incredibly common developmental defects.
“Second,” he says, “the question of how things form and develop in the kidney has major medical implications, and we cannot answer that with the ‘organ-on-a-chip’ approach. We need to create a model that mimics the chemical and mechanical properties of the kidney to watch these tissues develop.”
The fundamental development of the kidney can also answer other questions related to efficiency and the evolution of this biological filtration system.
“We have the tendency to believe that systems in the human body are the most evolved and thus the most efficient, but that is not necessarily true,” says Hughes. “If we can better understand the development of a system, such as the kidney, then we may be able to make the system better.”
Hughes’ kidney research will lay the foundation for broader goals within regenerative medicine and organ transplantation.
Researchers from Penn and CHOP detail the mechanism by which HIV infection blocks the maturation process of brain cells that produce myelin, a fatty substance that insulates neurons.
It’s long been known that people living with HIV experience a loss of white matter in their brains. As opposed to gray matter, which is composed of the cell bodies of neurons, white matter is made up of a fatty substance called myelin that coats neurons, offering protection and helping them transmit signals quickly and efficiently. A reduction in white matter is associated with motor and cognitive impairment.
In a new study using both human and rodent cells, the team has hammered out a detailed mechanism, revealing how HIV prevents the myelin-making brain cells called oligodendrocytes from maturing, thus putting a wrench in white matter production. When the researchers applied a compound blocking this process, the cells were once again able to mature.
“Even when people with HIV have their disease well-controlled by antiretrovirals, they still have the virus present in their bodies, so this study came out of our interest in understanding how HIV infection itself affects white matter,” says Kelly Jordan-Sciutto, a professor in Penn’s School of Dental Medicine and co-senior author on the study. “By understanding those mechanisms, we can take the next step to protect people with HIV infection from these impacts.”
“When people think about the brain, they think of neurons, but they often don’t think about white matter, as important as it is,” says Judith Grinspan, a research scientist at CHOP and the study’s other co-senior author. “But it’s clear that myelination is playing key roles in various stages of life: in infancy, in adolescence, and likely during learning in adulthood too. The more we find out about this biology, the more we can do to prevent white matter loss and the harms that can cause.”
Jordan-Sciutto and Grinspan have been collaborating for several years to elucidate how ART and HIV affect the brain, and specifically oligodendrocytes, a focus of Grinspan’s research. Their previous work on antiretrovirals had shown that commonly used drugs disrupted the function of oligodendrocytes, reducing myelin formation.
In the current study, they aimed to isolate the effect of HIV on this process. Led by Lindsay Roth, who recently earned her doctoral degree within the Biomedical Graduate Studies group at Penn and completed a postdoctoral fellowship working with Jordan-Sciutto and Grinspan, the investigation began by looking at human macrophages, one of the major cell types that HIV infects.
Kelly Jordan-Sciutto is vice chair and professor in the University of Pennsylvania School of Dental Medicine’s Department of Basic & Translational Sciences and is director of Biomedical Graduate Studies. She is a member of the Penn Bioengineering Graduate Group.