Month: February 2021

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BE Seminar: “Dissecting Multicellular Therapeutic Responses Using a Large-scale Single-cell Profiling Platform” (Siyu Chen)

Sisi Chen, Senior Research Scientist at CalTech, Pasadena, Calif. 1.23.20

Speaker: Siyu (Sisi) Chen, Ph.D.
Senior Research Scientist
Director of Beckman Institute Single-cell Profiling and Engineering Center
California Institute of Technology

Date: Thursday, February 25, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Dissecting Multicellular Therapeutic Responses Using a Large-scale Single-cell Profiling Platform”

Abstract:

Human diseases are fundamentally multicellular in nature with many different cell types contributing to disease progression and treatment response. However, how therapeutics impact each cell type in a heterogeneous population remains poorly understood because most studies are focused on isolated cell types or a handful of pathways. Now, single-cell transcriptional profiling methods allow us to collect a deep molecular portrait of the collective response of heterogeneous populations of cells to any perturbation. In my talk, I will present my research in harnessing the power of single-cell transcriptional profiling measurements to dissect therapeutic response in heterogeneous cell populations. In the first part, I will describe the probabilistic modeling framework I developed for analyzing single-cell population data across perturbations at scale (PopAlign). PopAlign models single-cell data with semantically interpretable, low-error, highly-compressed probabilistic models, which allows fast comparisons across hundreds of samples. In the second part, I will discuss how I applied this framework to analyze a drug response study of over 1.6M human primary immune cells to 500 commercially-available immunomodulatory compounds. While most compounds in the library exert broad impact across multiple cell types in the population, my analysis also reveals highly cell-type specific activity, including a novel myeloid-suppressing function of a group of compounds including NSAIDs and an artificial sweetener. My work provides new depth and insight into how existing compounds reshape immune populations, and a general platform for evaluating and designing population-level responses to therapeutic interventions.

Bio:

Sisi Chen is a Senior Research Scientist and the Director of the Beckman Single-cell Profiling and Engineering Center (SPEC) at Caltech, where she leads a team focused on single-cell technology development. She completed her B.S. in Electrical Engineering at MIT, and her Ph.D. in Bioengineering at UC-Berkeley/UCSF, where she was an NSF and NDSEG fellow working on microfluidic tools for single-cell biology. Most recently, she has developed a computational platform to analyze single-cell transcriptional data at large-scale, and has used this platform to map human immune system responses to hundreds of small molecule immunomodulatory compounds. Her research blends experimental and computational approaches to learning and controlling the collective response of multicellular tissues to therapeutic interventions.

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Penn Engineers’ New Bioprinting Technique Allows for Complex Microtissues

by Evan Lerner

Jason Burdick, Andrew C. Daly and Matthew Davidson

Bioprinting is currently used to generate model tissues for research and has potential applications in regenerative medicine. Existing bioprinting techniques rely on printing cells embedded in hydrogels, which results in low-cell-density constructs that are well below what is required to grow functional tissues. Maneuvering different kinds of cells into position to replicate the complex makeup of an organ, particularly at organlike cell densities, is still beyond their capabilities.

Now, researchers at the School of Engineering and Applied Science have demonstrated a new bioprinting technique that enables the bioprinting of spatially complex, high-cell-density tissues.

Using a self-healing hydrogel that allows dense clusters of cells to be picked and placed in a three-dimensional suspension, the researchers constructed a model of heart tissue that featured a mix of cells that mimic the results of a heart attack.

The study was led by Jason Burdick, Robert D. Bent Professor in the Department of Bioengineering, and Andrew C. Daly, a postdoctoral researcher in his lab. Fellow Burdick lab postdoc Matthew Davidson also contributed to the study, which has been published in the journal Nature Communications.

Even without a bioprinter, groups of cells can be made to clump into larger aggregates, known as spheroids. For Burdick and colleagues, these spheroids represented a potential building block for a better approach to bioprinting.

“Spheroids are often useful for studying biological questions that rely on the cells’ 3D microenvironments or in the construction of new tissues,” says Burdick. “However, we’d like to produce even higher levels of organization by ‘printing’ different kinds of spheroids in specific arrangements and have them fuse together into structurally complex microtissues.”

Read more at Penn Engineering Today.

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Arjun Yodh Named 2021 Michael S. Feld Biophotonics Award Recipient by The Optical Society

Arjun Yodh, Ph.D.

The Department of Phsyics in the Penn School of Arts & Sciences has announced that Arjun Yodh, Professor in Physics and Astronomy and member of the Bioengineering Graduate Group, was awarded the 2021 Michael S. Biophotonics Award by the Optical Society (OSA):

“He was selected for his ‘pioneering research on optical sensing in scattering media, especially diffuse optical and correlation spectroscopy and tomography, and for advancing the field of biophotonics through mentorship.’

The award ‘recognizes innovative and influential contributions to the field of biophotonics, regardless of career stage.'”

Read more about the award and Yodh’s research here.
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Penn Dental, Penn Engineering Unite to Form Center for Innovation & Precision Dentistry

by Beth Adams

With the shared vision to transform the future of oral health care, Penn Dental Medicine and Penn’s School of Engineering and Applied Sciences have united to form the Center for Innovation & Precision Dentistry (CiPD). The new Center marked its official launch on January 22 with a virtual program celebrating the goals and plans of this unique partnership. Along with the Deans from both schools, the event gathered partners from throughout the University of Pennsylvania and invited guests, including the National Institute of Dental and Craniofacial Research Director (NIDCR) Dr. Rena D’Souza and IADR Executive Director Chris Fox.

Conceived and brought to fruition by co-directors Dr. Michel Koo of Penn Dental Medicine and Dr. Kathleen Stebe of Penn Engineering, the CiPD is bridging the two schools through cutting-edge research and technologies to accelerate the development of new solutions and devices to address unmet needs in oral health, particularly in the areas of dental caries, periodontal disease, and head and neck cancer. The CiPD will also place a high priority on programs to train the next generation of leaders in oral health care innovation.

“We have a tremendous global health challenge. Oral diseases and craniofacial disorders affect 3.5 billion people, disproportionately affecting the poor and the medically and physically compromised,” says Dr. Koo, Professor in the Department of Orthodontics and Divisions of Community Oral Health and Pediatric Dentistry, in describing their motivation to form the Center. “There is an urgent need to find better ways to diagnose, prevent, and treat these conditions, particularly in ways that are affordable and accessible for the most susceptible populations. That is our driving force for putting this Center together.”

“We have united our schools around this mission,” adds Dr. Stebe, Richer & Elizabeth Goodwin Professor in the Department of Chemical and Biomolecular Engineering. “We have formed a community of scholars to develop and harness new engineering paradigms, to generate new knowledge, and to seek new approaches that are more effective, precise, and affordable to address oral health. More importantly, we will train a new community of scholars to impact this space.”

Born through Interdisciplinary Research

A serendipitous connection born through Penn’s interdisciplinary research environment itself brought Drs. Koo and Stebe together more than five years ago, an introduction that would eventually lead to creating the CiPD.

Dr. Tagbo Niepa, now assistant professor at the University of Pittsburgh, came to Penn Engineering in 2014 as part of Penn’s Postdoctoral Fellowship for Academic Diversity, an initiative from the office of the Vice Provost for Research. His studies on the microbiome led him to reach out to Dr. Stebe and Dr. Daeyeon Lee (also at Penn Engineering), and to connect them to Dr. Koo, initiating collaboration between their labs.

“Tagbo embodies what we are trying to do with the CiPD,” recalls Dr. Stebe. “He had initiative, he identified new tools and important context, and he did good science that may help us understand how to interrupt the disease process and identify new underlying mechanisms that can inspire new therapies.” Dr. Niepa worked on applying microfluidics and engineering to study the oral microbiome and better understand how the interactions between fungi and bacteria could impact dental caries.

“Upon meeting Michel, we became excited about the possibilities of bringing talent from the two schools together,” notes Dr. Stebe. A 2018 workshop organized by Drs. Koo and Stebe and funded by Penn’s Vice Provost of Research explored the potential for expanding cross-school research. “We invited researchers from dental medicine and engineering as well as relevant people from the arts and sciences to see if we could find a way to collaborate to advance oral and craniofacial health,” says Dr. Koo. “That was the catalyst for the Center; after the workshop, we put together a task force which would become the core members of the CiPD.”

In addition to Drs. Koo and Stebe, the CiPD Executive Committee includes Associate Directors Dr. Henry Daniell, Vice-Chair and W.D. Miller Professor, Department of Basic & Translational Sciences, Penn Dental Medicine, and Dr. Anh Le, Chair and Norman Vine Endowed Professor of Oral Rehabilitation, Department of Oral and Maxillofacial Surgery / Pharmacology, Penn Dental Medicine; as well as Dr. Andrew Tsourkas, Professor, Department of Bioengineering, Co-Director, Center for Targeted Therapeutics & Translational Nanomedicine (CT3N) and Chemical and Nanoparticle Synthesis Core, Penn Engineering; and Dr. Jason Moore, Edward Rose Professor of Informatics, Director of the Penn Institute for Biomedical Informatics. The core members of CiPD include 26 faculty from across both Penn Dental Medicine and Penn Engineering, and also from the Schools of Medicine and Arts & Sciences.

Read the full story in Penn Today.

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BE Seminar: “Engineering Synthetic Biomaterials for Islet Transplantation” (María M. Coronel)

Speaker: María M. Coronel, Ph.D.
Postdoctoral Fellow, the George W. Woodruff School of Mechanical Engineering
Georgia Institute of Technology

Date: Thursday, February 18, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Engineering Synthetic Biomaterials for Islet Transplantation”

Abstract:

Two major challenges to the translation of cellular-based tissue-engineered therapies are the lack of adequate oxygen support post-implantation and the need for systemic immunosuppression to halt the strong inflammatory and immunological response of the host. As such, strategies that aim at addressing oxygen demand, and local immunological responses can be highly beneficial in the translation of these therapies. In this seminar, I will focus on two biomaterial strategies to create a more favorable transplant niche for pancreatic islet transplantation. The first half will describe an in-situ oxygen-releasing biomaterial fabricated through the incorporation of solid peroxides in a silicone polymer. The implementation of this localized, controlled and sustained oxygen-generator mitigates the activation of detrimental hypoxia-induced pathways in islets and enhances the potency of extrahepatic 3D islet-loaded devices in a diabetic animal model. In the second part, I will focus on engineering synthetic biomaterials for the delivery of immunomodulatory signals for transplant acceptance. Biomaterial carriers fabricated with polyethylene glycol microgels are used to deliver immunomodulatory signals to regulate the local microenvironment and prevent allograft rejection in a clinically relevant pre-clinical transplant model. The use of synthetic materials as an off-the-shelf platform, without the need for manipulating the biological cell product, improves the clinical translatability of this engineered approach. Designing safer, responsive biomaterials to boost the delivery of targeted therapeutics will significantly reinvigorate interventional cell-based tissue-engineered therapies.

Bio:

Dr. María M. Coronel is currently a Juvenile Diabetes Research Foundation postdoctoral fellow at the Georgia Institute of Technology. Dr. Coronel completed her BS degree in Biomedical Engineering from the University of Miami, and her Ph.D. degree in Biomedical Engineering from the University of Florida as a National Institute of Health predoctoral fellow. Her doctoral work focused on engineering oxygen-generating materials for addressing the universal challenge of hypoxia within three-dimensional tissue-engineered implants. As a postdoctoral fellow, her research interest focus on engineering tools and principles to understand, stimulate, and modulate the immune system to develop controlled targeted interventional therapies. In addition to research, Dr. Coronel aims to be an advocate for diversity and inclusion in STEM as the co-president of the postdoctoral group and a founding member of the diversity, equity, and inclusion committee in bioengineering at Georgia Tech. Outside of the lab María enjoys cooking, baking, and traveling.

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Alumni Spotlight: Danielle Rossi

Danielle Rossi (M.S.E. 2018)

Danielle Rossi earned her M.S.E. in Bioengineering in December 2018 and is now a R&D Leadership and Development Program Engineer with Johnson & Johnson Medical Devices. Here she reminisces about her research opportunities at Penn and her fond memories of Philly.

“When I first started at Penn, I was amazed by all of the opportunities to learn, to challenge myself, to network, and to innovate. My time at Penn was filled with interesting classes, dedicated faculty, challenging problems to solve, and collaboration. From writing a mock NIH research grant for a tissue engineered Intervertebral Disk in BE 553, to designing an electromechanical device controlled with muscle movement in BE 570, to writing up a business plan and pitching to investors in EAS 546, every new day came with a new venture.

On top of the exciting classes and projects, Penn has numerous research labs and healthcare facilities so that students can apply their skills to real-world problems. While I was a student, I had the opportunity to work at the Abramson Cancer Center in the Cancer Risk Evaluation Program. The program focused on patient risk evaluations, including genetic testing for certain cancers such as breast, ovarian, and sarcoma. This exposed me to the healthcare environment and gave me a new perspective on preemptive medicine.

During my free time, I loved to tour the historically and culturally rich city of Philadelphia. I have the fondest memories of exploring the city with my BE friends and storming the Philly streets when the Eagles won the Super Bowl!

While at Penn, I was sure to utilize Career Services to help me spruce up my resume and interview skills. I was lucky enough to meet with Johnson & Johnson Medical Devices at a Penn career fair and was offered a spot in the R&D Leadership and Development Program. The program allows me to rotate through three different J&J Medical Device companies as an R&D Engineer to gain exposure to new product development, mechanical design, computational modeling, manufacturing, design quality and more. ”

This post is part of BE’s Alumni Spotlight series. Read more testimonies from BE Alumni on the BE website.

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BE Seminar: “Multi-input Chemical Control with Computationally Designed Proteins for Research Tools and Cell Therapies” (Glenna Wink Foight)

Speaker: Glenna Wink Foight, Ph.D.
Senior Scientist
Lyell Immunopharma

Date: Thursday, February 11, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Multi-input Chemical Control with Computationally Designed Proteins for Research Tools and Cell Therapies”

Abstract:

Protein modules that are responsive to small molecule inputs have enabled control of cellular processes for decades’ worth of important mechanistic studies. More recently, they have gained attention as a means of control for improved safety of cellular therapies. To date, most small molecule-responsive systems have been adapted from natural proteins, which provide limited control behaviors and often rely on small molecules with non-ideal properties for use in humans. I will describe how we have used computational protein design to move beyond these naturally occurring systems to create a new set of molecular tools that are responsive to multiple clinically approved drugs. The unique architecture of our system enables more complex control behaviors for multiple cellular outputs. I will describe applications of this designed system in the control of mammalian cytoskeletal signaling, transcription, and CAR T-cell therapy.

Bio:

Dr. Glenna Foight is a Senior Scientist at Outpace Bio, where she leads a team that focuses on engineering small molecule drug-based control of cell therapies. Her work at the startups Outpace Bio and Lyell Immunopharma has involved the adaptation of technologies that she developed as a Washington Research Foundation Innovation Postdoctoral Fellow at the University of Washington. Dr. Foight received her Ph.D. in Biology from MIT and her B.S. in Biochemistry from North Carolina State University. Her background is in applying protein design and engineering to develop novel molecular interventions and control strategies for applications in basic research, cancer, and cell therapy.

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Penn Bioengineers Develop Implantable Living Electrodes

Living Electrode Panels (image courtesy of the Cullen Lab)

Connecting the human brain to electrical devices is a long-standing goal of neuroscientists, bioengineers, and clinicians, with applications ranging from deep brain stimulation (DBS) to treat Parkinson’s disease to more futuristic endeavors such as Elon Musk’s NeuraLink initiative to record and translate brain activity. However, these approaches currently rely on using implantable metallic electrodes that inherently provoke a lasting immune response due to their non-biological nature, generally complicating the reliability and stability of these interfaces over time. To address these challenges, D. Kacy Cullen, Associate Professor in Neurosurgery and Bioengineering, and Dayo Adewole, a doctoral candidate in Bioengineering, worked with a multi-disciplinary team of collaborators to develop the first “living electrodes” as an implantable, biological bridge between the brain and external devices. In a recent article published in Science Advances, the team demonstrated the fabrication of hair-like microtissue comprised of living neuronal networks and bundled tracts of axons — the signal sending fibers of the nervous system — protected within soft hydrogel cylinders. They showed that these axon-based living electrodes could be fully controlled and monitored with light — thus eliminating the need for electrical contact — and are capable of surviving and forming synapses with the brain as demonstrated in an adult rat model. While further advancements are necessary prior to clinical use, the current findings provide the foundation for a new class of “living electrodes” as a biological intermediary between humans and devices capable of leveraging natural mechanisms to potentially provide a stable interface for clinical applications.

Cullen has a primary appointment in the Department of Neurosurgery in the Perelman School of Medicine, with a secondary appointment in the Department of Bioengineering in the School of Engineering and Applied Science, and an appointment in the Corporal Michael J. Crescenz VA Medical Center in Philadelphia.

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Maria Ovando: Research and Self-discovery

by Elisa Ludwig

Maria Ovando

The process of discovery sometimes starts with a hunch. Maria Ovando arrived at Penn Engineering with an affinity for math and science, extensive experience volunteering at her local health clinic and an assumption that she was preparing for a career in medicine. She was drawn to Penn Engineering because of the flexibility in the curriculum and the ability to both tailor her course of study and pursue cross-disciplinary subjects.

As a pre-med student, bioengineering seemed to be the natural choice for a major, but during her freshman year, Ovando found that she genuinely enjoyed bioengineering as a discipline in its own right, and only then did her future goals come into view.

“I’ve discovered that I have a passion for research, working on low-cost devices that can have a direct impact on individuals,” she says.

One of the most important opportunities she’s had at Penn is her work with Dr. Michelle J. Johnson at the Rehabilitation Robotics Lab in the Perelman School of Medicine. There, Ovando has been working to improve aspects of the Community-based Affordable Robot Exercise System, which helps stroke patients with lower extremity impairment. She’s also worked on a project that involved analyzing and reevaluating data in the early detection of cerebral palsy in infants. As an undergraduate, she found it both meaningful and moving to have a role in this groundbreaking research.

Read the full story in Penn Engineering today.