Much of the world, including research at Penn Medicine, has focused its attention on how T cells–which play a central role in immune response—might shape the trajectory of COVID-19 infection, and how immunotherapy can shed light on treatment of the disease.
Already a leader in immunotherapy research and treatment, Penn Medicine pioneered the groundbreaking development of CAR T cell cancer therapy. Avery Posey, an assistant professor of systems pharmacology and translational therapeutics, trained as a postdoctoral fellow in the lab of Carl June, who pioneered CAR T cell immunotherapy to treat cancer. Now as a faculty member at Penn, Posey has maintained a focus on T cell therapeutics, mostly for the treatment of cancer.
“This research combines two of my biggest interests—the use of gene therapy to treat disease and the investigation of little known biology, such as the roles of glycans in cell behavior. The pursuit of new knowledge, the roads less traveled—those are my inspirations,” Posey says.
To combat the COVID-19 pandemic caused by the SARS-CoV2 virus, Dr. Andrew Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine (Titan) Lab in Penn Bioengineering, in collaboration with the Penn-based startup, AlphaThera, was recently awarded a $667,000 SBIR Phase II Grant Extension to support its efforts in commercializing COVID-19 detection technology. The grant supports work to address the growing need for anti-viral antibody testing. Specifically, the Tsourkas Lab and AlphaThera hope to leverage their expertise with antibody conjugation technologies to reduce the steps and complexity of existing detection assays to enable greater production and higher sensitivity tests. AlphaThera was founded in 2016 by Andrew Tsourkas, PhD, Professor of Bioengineering and James Hui, MD, PhD, a graduate of the Perelman School of Medicine and Penn Bioengineering’s doctoral program.
During this pandemic it is crucial to characterize disease prevalence among populations, understand immunity, test vaccine efficacy and monitor disease resurgence. Projections have indicated that millions of daily tests will be needed to effectively control the virus spread. One important testing method is the serological assay: These tests detect the presence of SARS-CoV2 antibodies in a person’s blood produced by the body’s immune system responding to infection. Serological tests not only diagnose active infections, but also establish prior infection in an individual, which can greatly aid in forecasting disease spread and contact tracing. To perform the serological assays for antibody detection, well-established immunoassay methods are used such as ELISA.
A variety of issues have slowed the distribution of these serological assays for antibody testing. The surge in demand for testing has caused shortages in materials and reagents that are crucial for the assays. Furthermore, complexity in some of the assay formats can slow both production and affect the sensitivity of test results. Recognizing these problems, AlphaThera is leveraging its novel conjugation technology to greatly improve upon traditional assay formats.
With AlphaThera’s conjugation technology, the orientation of antibodies can be precisely controlled so that they are aligned and uniformly immobilized on assay detection plates. This is crucial as traditional serological assays often bind antibodies to plates in a non-uniform manner, which increases variability of results and reduces sensitivity. See Fig 1 below. With AlphaThera’s uniform antibody immobilization, assay specificity could increase by as much as 1000- fold for detection of a patient’s SaRS-CoV2 antibodies.
Furthermore, AlphaThera is addressing the shortage of assay reagents, specifically secondary antibody reagents, by removing certain steps from traditional serological assays. Rather than relying on secondary antibodies for detection of the patient antibodies, AlphaThera’s technology can label the patient SaRS-CoV2 primary antibodies directly in serum with a detection reagent. This eliminates several processing steps, reducing the time of the assay by as much as 50%, as well as the costs.
The Tsourkas Lab and AlphaThera have initiated their COVID-19 project, expanding into the Pennovation Center and onboarding new lab staff. Other antibody labeling products have also become available and are currently being prepared for commercialization. Check out the AlphaThera website to learn more about their technology at https://www.alphathera.com.
NIH SBIR Phase II Grant Extension— 5-R44-EB023750-03 (PI: Yu) — 10/07/2020 – 10/07/2021
The first lecture in the Fall 2020 Penn Bioengineering Seminar Series will be held Thursday, September 10th. All seminars this semester will be held virtually on Zoom.
Speaker: Quinton Smith, Ph.D.
Laboratory for Multiscale Regenerative Technologies
Massachusetts Institute of Technology
Date: Thursday, September 10, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact firstname.lastname@example.org
Title: “Stem Cell Fate is a Touchy Subject”
The success of regenerative cell therapy relies on the integration of a functional vascular system within the redeveloping tissue, to mediate the exchange of oxygen, nutrients and waste. Although the advent of human induced pluripotent stem cells (hiPSCs) has accelerated progress towards this goal, owing to their potential to generate clinically relevant scales of patient-specific cells, techniques to drive their specification mainly rely on chemical cues. In this seminar, I will discuss engineering strategies to control the complex stem cell extracellular milieu, emphasizing the importance of mechanical cues during hiPSC development, specification and downstream functionality as it relates to vascular differentiation.
Quinton Smith received his PhD in Chemical and Biomolecular Engineering from Johns Hopkins University in 2017 after completing his bachelor’s degree in Chemical Engineering from the University of New Mexico. As a graduate student under the guidance of Dr. Sharon Gerecht, Quinton implemented various engineering tools to explore the roles of physical and chemical cues on stem cell lineage specification and downstream maturation. Dr. Smith is currently a postdoctoral fellow under the mentorship of Dr. Sangeeta Bhatia at MIT’s Koch Institute for Integrative Cancer Research, where he is investigating the role biliary epithelium in liver regeneration. Dr. Smith’s predoctoral work was supported by an NIH/NHLBI F-31 and NSF Graduate Research Fellowship. He is a recipient of the 2017 Siebel Scholar award, and most recently joined the class of 2018 HHMI Hanna Gray Fellows.
See the full list of upcoming Penn Bioengineering fall seminars here.
The Chan Zuckerberg Initiative’s Collaborative Pairs Pilot Project Award is part of its Neurodegeneration Challenge Network
More than 30 inherited disorders are caused by the unstable expansion of repetitive DNA sequences, including Huntington’s disease, ALS, Fragile X syndrome, and Friedreich’s ataxia. Jennifer E. Phillips-Cremins, associate professor in Penn Engineering’s Department of Bioengineering and in the Perelman School of Medicine’s Department of Genetics, has shown another link between these disorders: the location of these expanding genes relative to the complicated folding patterns the genome exhibits to fit inside the nucleus of a cell.
Now, Phillips-Cremins is among 60 researchers taking part in a $4.5 Million Chan Zuckerberg Initiative project that aims to apply novel, interdisciplinary approaches toward investigating neurodegenerative disorders. The CZI Collaborative Pairs Pilot Project will fund 30 teams that combine clinical and basic science expertise and have at least one early- or mid-career researcher.
In a ‘Wired’ feature, Bassett helps explain the growing field of network neuroscience and how the form and function of the brain are connected.
Early attempts to understand how the brain works included the pseudoscience of phrenology, which theorized that various mental functions could be determined through the shape of the skull. While those theories have long been debunked, modern neuroscience has shown a kernel of truth to them: those functions are highly localized to different regions of the brain.
Now, Danielle Bassett, Professor of J. Peter Skirkanich Professor of Bioengineering and Electrical and Systems Engineering, is pioneering a new subfield that goes even deeper into the connection between the brain’s form and function: network neuroscience.
In a recent feature article in Wired, Bassett explains the concepts behind this new subfield. While prior understanding has long relied on the idea that certain areas of the brain control certain functions, Bassett and other network neuroscientists are using advances in imaging and machine learning to reveal the role the connections between those areas play.
For Bassett, one of the first indicators that these connections mattered more than previously realized was the shape of the neurons themselves.
Speaking with Wired’s Grace Huckins, Bassett says:
“Neurons are not spherical — neurons have a cell body, and then they have this long tail that allows them to connect to many other cells. You can even look at the morphology of the neuron and say, ‘Oh, well, connectivity has to matter. Otherwise, it wouldn’t look like this.’”
Read more about Bassett and the field of network neuroscience in Wired.
Rising Bioengineering Sophomore Catherine Michelluti (BSE 2023) has been featured on Penn’s SNF Paideia Program Instagram which discusses her diverse interests in machine learning in medicine, computer science, playing the violin and more. Catherine is a pre-med student who is pursuing an uncoordinated dual degree between the School of Engineering and Applied Science and the Wharton School of Business (BS in Economics 2023). She is also an incoming fellow in the SNF Paideia Program, which is supported by the Stavros Niarchos Foundation, is an interdisciplinary program which “encourage[s] the free exchange of ideas, civil and robust discussion of divergent views, and the integration of individual and community wellness, service, and citizenship through SNF Paideia designated courses, a fellows program, and campus events” (SNF Paideia website).
Taylor got her BS in Biomedical Engineering from the University of Virginia where she conducted research under Drs. Cato Laurencin and Edward Botchwey (the latter got his PhD in Penn Bioengineering in 2002). She went on to complete her PhD in Biomedical Engineering in 2016, studying with Dr. Joseph Freeman, in the Musculoskeletal Tissue Regeneration Laboratory at Rutgers University. During her time at Penn, she served as the Co-President of the Biomedical Postdoctoral Council, worked with the Perelman School of Medicine’s PennVIEW program on postdoctoral diversity recruitment, and spearheaded the mentoring circles program, which brings together postdoctoral researchers, graduate students, and undergraduates in informal groups that allow mentorship and learning to flow freely.
The foundation for Taylor’s research interests is a combination of her training in bone tissue engineering, bioactive biomaterials, and tendon injury and repair. Her graduate research focused on a three-dimensional biomimetic pre-vascularized scaffold that simultaneously promoted osteogenic and angiogenic differentiation of human mesenchymal stem cells in vitro and cellular infiltration and neovascularization in vivo without the addition of growth factors of cells. As a postdoctoral fellow, in addition to investigating the role of collagen type V on tendon inflammation and remodeling in a mouse patellar tendon injury model, she also elucidated the biological and mechanical implications of an implantable bilayer delivery system (BiLDS) for controlled and localized release of non-steroidal anti-inflammatory drugs (NSAIDs) to modulate tendon inflammation in a rat rotator cuff injury and repair model. This collection of work exploits the ability of these transformative technologies to provide physical and chemical regenerative cues without the use of exogenous cells; hence avoiding possible complications associated with autologous and allogeneic cell sources and simplifying the regulatory pathway towards clinical application. Taylor’s future research program at the University of Florida will focus on tailored cell-free combinatorial strategies, such as decellularized matrices, tunable delivery systems, and modified extracellular vesicles, to complement and improve the native musculoskeletal tissue regenerative and reparative process.
“Brittany has been an amazing postdoctoral fellow,” says her mentor Louis Soslowsky. “She has learned a lot and contributed to various projects in an exemplary manner. She has been a leader in many arenas here at Penn and I am so proud of what she has done so far. I look forward to following her continued accomplishments at the University of Florida! I know she’ll do great!”
“I am grateful for the opportunity to complete my postdoctoral training at Penn,” Taylor says:
“[P]articularly in a lab that is affiliated with the Penn Bioengineering program and the Department of Orthopaedic Surgery, where I had the unique experience of addressing basic science questions using translational animal models, while utilizing my engineering background and having a direct interaction with clinicians. Additionally, I connected with some amazing people here at Penn who had a significant impact on my time at Penn, and will be lifelong friends, colleagues, and mentors.”
Congratulations Dr. Taylor from everyone at Penn Bioengineering!
Danielle Bassett, J. Peter Skirkanich Professor in the departments of Bioengineering and Electrical and Systems Engineering, has been called the “doyenne of network neuroscience.” The burgeoning field applies insights from the field of network science, which studies how the structure of networks relate to their performance, to the billions of neuronal connections that make up the brain.
Much of Basset’s research draws on mathematical and engineering principles to better understand how mental traits arise, but also applies them more broadly to other challenges in neuroscience.
The researchers used machine learning techniques to create a new classification system for neurodegenerative diseases, one which may redraw the boundaries between them and help explain clinical differences in patients who received the same diagnoses.
BioWorld’s Anette Breindl spoke with Bassett about the team’s findings.
Now, investigators have developed a new approach to classifying neurodegenerative disorders that used the overall patterns of protein aggregation, rather than specific proteins, to define six clusters of patients that crossed traditional diagnostic categories.
“We find that perhaps the way that clinicians have been diagnosing these disorders… is not necessarily the way these disorders work,” Danielle Bassett told BioWorld. “The way we’ve been trying to carve nature at joints is not the way that nature has joints. The joints are elsewhere.”
Continue reading Breindl’s article, “For neurodegeneration, a different way to slice the pie,” at BioWorld.
The BWF CASI Career Awards provide $500,000 over five years to bridge advanced postdoctoral training and the first three years of faculty service; and to foster the early career development of researchers who have transitioned from physical/mathematical/computational sciences or engineering into the biological sciences, and who are dedicated to pursuing a career in academic research. Goyal is one of just eight recipients of the 2020-2025 CASI award.
Goyal’s research work is centered around developing novel mathematical and experimental frameworks to study how a rare subpopulation of cancer cells are able to survive drug therapy and develop resistance, resulting in relapse in patients. In particular, his work will provide a view of different paths that single cancer cells take when becoming resistant, at unprecedented resolution and scale. In turn, this will help devise novel therapeutic strategies to combat the challenge of drug resistance in cancer.
“I am very excited to be a part of the community of the Burroughs Wellcome Fund CASI award past and present recipients, which also includes my postdoctoral adviser Arjun Raj, who received this award in 2008,” Goyal says. “This CASI award will help provide me with the freedom to pursue high risk research directions as I transition to faculty. I feel fortunate to be surrounded by kind and supportive colleagues in the Bioengineering Department at Penn, an environment that has been critical for my interdisciplinary journey as a scientist.”
Among the key faculty involved in this new center is J. Peter Skirkanich Professor of Bioengineering Danielle Bassett. Bassett’s Complex Systems Lab studies biological, physical, and social systems by using and developing tools from network science and complex systems theory. Bassett, along with Assistant Professor of Psychiatry Desmond Oathes, will work to:
understand how TMS [i.e. transcranial magnetic stimulation] might improve working memory in healthy adults and those with ADHD by combining network control theory (a set of concepts and principles employed in engineering), magnetic stimulation of the brain, and functional brain imaging.