Sherry (Xue) Gao, Presidental Penn Compact Associate Professor in Chemical and Biomolecular Engineering and in Bioengineering
Sherry (Xue) Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE), always knew she had a future in the lab. “I grew up in China, and when I was little, maybe six or seven,” she recalls, “my teacher asked me, ‘What do you want to be when you grow up?’ I said, ‘I want to be a scientist!’”
Neither of her parents had studied beyond high school; when Gao finished her training as a chemical engineer, she became the first person in her family to graduate from college. “One of my greatest motivations is to help first-generation college students,” Gao says.
Now, as the newest faculty member in CBE, Gao is prepared to do just that: support the next generation of chemical engineers, while also conducting groundbreaking research in the development of small molecules to edit genes, pushing the boundaries of precision medicine.
The Presidential Penn Compact Professorships were created by former Penn President Amy Gutmann specifically to recruit and support faculty like Gao: transformative leaders working at the intersection of multiple fields with “a yen for collaboration,” as Gutmann told the Penn Gazette in 2021.
Gao joins Penn Engineering from Rice University, where she collected numerous accolades, including the 2024 BMES-CMBE Rising Star Award, a 2022 NSF CAREER Award, the 2022 Outstanding Young Faculty at Rice School of Engineering Award and the 2020 NIH MIRA R35 Award.
As a member of the Center for Precision Engineering for Health (CPE4H), Gao will partner with colleagues from across the School to develop technologies that bridge disciplines, all in the interest of advancing health care. “We are very excited to have Sherry as a new member of the Center,” says Daniel Hammer, Alfred G. and Meta A. Ennis Professor and inaugural Director of CPE4H. “Gene editing is an important new tool that can precisely alter cell behavior by deleting or redirecting cell pathways, as well as enhancing and suppressing gene expression. She will have significant interactions with other members of the Center, such as Mike Mitchell and myself, as well as the broader Penn community, especially with the CAR therapists.”
TDP-43 may be one of the most dangerous proteins in the human body, implicated in neurodegenerative conditions like ALS and Alzheimer’s disease. But the protein remains mysterious: how TDP-43 interacts with the immune system, for instance, is still unclear.
Now, Ning Jenny Jiang, J. Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering, has been selected for the Collaborative Pairs Pilot Project Awards, sponsored by the Chan Zuckerberg Initiative (CZI), to investigate the relationship between TDP-43 and the immune system.
Launched in 2018, the Collaborative Pairs Pilot Project Awards support pairs of investigators to explore “innovative, interdisciplinary approaches to address critical challenges in the fields of neurodegenerative disease and fundamental neuroscience.” Professor Jiang will partner with Pietro Fratta, MRC Senior Clinical Fellow and MNDA Lady Edith Wolfson Fellow at the University College London Queen Square Institute of Neurology.
The TDP-43 protein is associated with neurodegenerative diseases affecting the central nervous system, including ALS and Alzehimer’s disease. While the loss of neurons and muscle degeneration cause the progressive symptoms, the diseases themselves may be a previously unidentified trigger for abnormal immune system activity.
One possible link is the intracellular mislocalization of TDP-43 (known as TDP-43 proteinopathy), when the protein winds up in the wrong location, which the Jiang and Fratta Labs will investigate. Successfully proving this link could result in potentially game-changing new therapies for these neurodegenerative diseases.
The Jiang Lab at Penn Engineering specializes in systems immunology, using high-throughput sequencing and single-cell and quantitative analysis to understand how the immune system develops and ages, as well as the molecular signatures of immune related diseases. Jiang joined Penn Bioengineering in 2021.
Since arriving on campus, Jiang has teamed with the recently formed Penn Anti-Cancer Engineering Center (PACE), which seeks to understand the forces that determine how cancer grows and spreads, and Engineers in the Center for Precision Engineering (CPE4H), which focuses on innovations in diagnostics and delivery in the development of customizable biomaterials and implantable devices for individualized care.
Jiang was elected a member of the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows in 2021, and has previously won multiple prestigious awards including the NSF CAREER, a Cancer Research Institute Lloyd J. Old STAR Award, and a CZI Neurodegeneration Challenge Network Ben Barres Early Career Acceleration Award.
Jiang is a leader in high-throughput and high-dimensional analysis of T cells, a type of white blood cell crucial to the functioning of a healthy immune system. A recent study in Nature Immunology described the Jiang Lab’s TetTCR-SeqHD technology, the first approach to provide a multifaceted analysis of antigen-specific T cells in a high-throughput manner.
The CZI Collaborative Pairs Pilot Project Awards will provide $200,000 of funding over 18 months with a chance to advance to the second phase of $3.2 million in funding over a four-year period.
Read the full list of grantees on the CZI’s Neurodegeneration Challenge Network (NDCN) Projects website here.
Engineers in the Center for Precision Engineering for Health (CPE4H) are focusing on innovations in diagnostics and delivery, cellular and tissue engineering, and the development of new devices that integrate novel materials with human tissues. Below is an excerpt from “Going Small to Win Big: Engineering Personalized Medicine,” featuring the research from the laboratory of Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering.
The Challenge
Solid tumors evade the immune system’s ability to attack them in part due to the tumors’ tough, fibrous biological barriers that circulating immune cells can’t cross. Researchers need to identify ways to deliver individualized treatments that can better target these tumors without causing damage to healthy tissues or affecting overall quality of life.
The Status Quo
Current cancer treatments typically involve surgery, radiation or chemo- therapy to eliminate solid tumors. These treatments are invasive and can cause numerous negative downstream effects. Newer treatments involve engineering a patient’s immune system to recognize and fight cancerous cells, but are so far only effective against certain “liquid” cancers, where the mutated cells circulate freely in the blood and bone marrow and are small enough to be picked off by the patient’s upgraded T cells. Additionally, existing methods can also require that the cell engineering take place in a lab rather than directly inside the body.
The Mitchell Lab’s Fix
Members of the lab of Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering, are looking to utilize nanoparticle delivery technology developed by their lab to engineer a different type of immune cell, the macrophage, in order to fight solid- tumor cancers from the inside.
The Mitchell lab is using lipid nanoparticles (LNPs) to carry mRNA and DNA sequences inside of macrophages, a type of immune cell that can consume tumor cells if engineered correctly. In theory, a patient would receive an injection carrying the LNP payload, and the macrophages, whose name literally means “big eaters,” would take up the genetic sequence, alter their function and be able to recognize a patient’s own unique tumor cells in the body.
Because of the way macrophages operate, they could cross the tumor’s biological barrier and attack the cells, destroying the tumor from the inside. An added benefit of the Mitchell Lab’s technology is that the destroyed tumor cells would then also allow other immune cells to present their antigens to circulating T cells, which could then learn to fight those same cancer cells in the future.
“One of the longstanding challenges that we face in the context of cancer and immunotherapies is that every tumor has unique antigens that are specific to patients,” says Mitchell. “This is why we’ve had a lot of trouble developing targeted therapies. Personalizing an approach by harnessing an individual’s immune system gives each patient a greater chance of a positive outcome.”
Engineers in the Center for Precision Engineering for Health (CPE4H) are focusing on innovations in diagnostics and delivery, cellular and tissue engineering, and the development of new devices that integrate novel materials with human tissues. Below is an excerpt from “Going Small to Win Big: Engineering Personalized Medicine,” featuring the research from the laboratory of Jenny Jiang, J. Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering.
The Challenge
In order to create personalized immune therapies, researchers need to untangle what is happening between an individual patient’s immune cells and the antigens that they interact with on a molecular level. Immune cell-antigen interactions need to be understood in four different areas in order to create a full picture: the unique genetic sequence of the T cell’s antigen receptors, the antigen specificity of that cell, and both the gene and protein expression of the same cell.
The Status Quo
Prior methods of understanding interactions between T cells and antigens could only get a picture of one or two of these four elements because of technology constraints. Other roadblocks included that cells cultured or engineered in a laboratory setting are not in a natural environment so they won’t express genes or proteins in the way T cells would in the body, and technologies that assess the antigen specificity of T cells were not cost-effective for looking at large numbers of antigens.
The Jiang Lab’s Fix
The lab of Jenny Jiang, J. Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering, developed a technology called TetTCR-SeqHD, which solves these problems. Using this technology, scientists can now simultaneously profile samples of large numbers of single T cells in the four dimensions using high- throughput screening.
The Jiang Lab’s technology is essentially a method for getting a “full-body scan” of an individual’s T cells and creates a catalog of the different types of T cells and the antigens they respond (or don’t respond) to, paving the way for the ability to better target immune therapies to an individual patient.
“Individual T cells are unique, and that’s the challenge of using one treatment to fit all,” says Jiang. “Identifying antigen specificity and creating therapies that target that specificity in an individual’s T cells will be key to truly personalizing immune therapies in the future.”
CPE4H is one of the focal points of Penn Engineering signature initiative on Engineering Health.
The Penn Center for Precision Engineering for Health (CPE4H) was established late last year to accelerate engineering solutions to significant problems in healthcare. The center is one of the signature initiatives for Penn’s School of Engineering and Applied Science and is supported by a $100 million commitment to hire faculty and support new research on innovative approaches to those problems.
Acting on that commitment, CPE4H solicited proposals during the spring of 2022 for seed grants of $80K per year for two years for research projects that address healthcare challenges in several key areas of strategic importance to Penn: synthetic biology and tissue engineering, diagnosis and drug delivery, and the development of innovative devices. While the primary investigators (PIs) for the proposed projects were required to have a primary faculty appointment within Penn Engineering, teams involving co-PIs and collaborators from other schools were eligible for support. The seed program is expected to continue for the next four years.
“It was a delight to read so many novel and creative proposals,” says Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and the Inaugural Director of CPE4H. “It was very hard to make the final selection from a pool of such promising projects.”
Judged on technical innovation, potential to attract future resources, and ability to address a significant medical problem, the following research projects were selected to receive funding.
Evolving and Engineering Thermal Control of Mammalian Cells
Led by Lukasz Bugaj, Assistant Professor in Bioengineering, this project will engineer molecular switches that can be toggled on and off inside mammalian cells at near-physiological temperatures. Successful development of these switches will provide new ways to communicate with cells, an advance that could be used to make safer and more effective cellular therapies. The project will use directed evolution to generate and find candidate molecular tools with the desired properties. Separately, the research will also develop new technology for manipulating cellular temperature in a rapid and programmable way. Such devices will enhance the speed and sophistication of studies of biological temperature regulation.
A Quantum Sensing Platform for Rapid and Accurate Point-of-Care Detection of Respiratory Viral Infections
Combining microfluidics and quantum photonics, PI Liang Feng, Professor in Materials Science and Engineering and Electrical and Systems Engineering, Ritesh Agarwal, Professor in Materials Science Engineering, and Shu Yang, Joseph Bordogna Professor in Materials Science and Engineering and Chemical and Biomolecular Engineering, are teaming up with Ping Wang, Professor of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine, to design, build and test an ultrasensitive point-of-care detector for respiratory pathogens. In light of the COVID-19 pandemic, a generalizable platform for rapid and accurate detection of viral pathogenesis would be extremely important and timely.
Versatile Coacervating Peptides as Carriers and Synthetic Organelles for Cell Engineering
PI Amish Patel, Associate Professor in Chemical and Biomolecular Engineering, and Matthew C. Good, Associate Professor of Cell and Developmental Biology in the Perelman School of Medicine and in Bioengineering, will design and create small proteins that self-assemble into droplet-like structures known as coacervates, which can then pass through the membranes of biological cells. Upon cellular entry, these protein coacervates can disassemble to deliver cargo that modulates cell behavior or be maintained as synthetic membraneless organelles. The team will design new chemistries that will facilitate passage across cell membranes, and molecular switches to sequester and release protein therapeutics. If successful, this approach could be used to deliver a wide range of macromolecule drugs to cells.
Towards an Artificial Muscle Replacement for Facial Reanimation
Cynthia Sung, Gabel Family Term Assistant Professor in Mechanical Engineering and Applied Mechanics and Computer Information Science, will lead a research team including Flavia Vitale, Assistant Professor of Neurology and Bioengineering, and Niv Milbar, Assistant Instructor in Surgery in the Perelman School of Medicine. The team will develop and validate an electrically driven actuator to restore basic muscle responses in patients with partial facial paralysis, which can occur after a stroke or injury. The research will combine elements of robotics and biology, and aims to produce a device that can be clinically tested.
“These novel ideas are a great way to kick off the activities of the center,” says Hammer. “We look forward to soliciting other exciting seed proposals over the next several years.”
Earlier this year, Penn President Amy Gutmann and Vijay Kumar, Nemirovsky Family Dean of Penn’s School of Engineering and Applied Science, announced a $100 million commitment to accelerate innovations in medical technologies. Called the Center for Precision Engineering for Health (CPE4H), the initiative aims to bring together researchers from a wide range of fields to develop customizable biomaterials and implantable devices that can be tailored for individualized diagnostics, treatments and therapies.
Now, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Penn Engineering’s Departments of Bioengineering and Chemical and Biomolecular Engineering, has been named CPE4H’s inaugural director.
“Penn is a unique environment where innovations in healthcare can emerge very rapidly, as we’ve seen with the development of CAR-T cancer immunotherapy, and the design and delivery of mRNA vaccines,” Hammer says. “Engineering plays a central role in making those technologies functional and maximizing their impact, and CPE4H is a golden opportunity to take these technologies to the next level in a way that actually helps people.”
