Nerve Repair, With Help From Stem Cells

A cross-disciplinary Penn team is pioneering a new approach to peripheral nerve repair.

In a new publication in the journal npj Regenerative Medicine, a team of Penn researchers from the School of Dental Medicine and the Perelman School of Medicine “coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors,” addressing the need for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. The study was led by Anh Le, Chair and Norman Vine Endowed Professor of Oral Rehabilitation in the Department of Oral and Maxillofacial Surgery/Pharmacology at the University of Pennsylvania School of Dental Medicine, and was co-authored by D. Kacy Cullen, Associate Professor in Neurosurgery at the Perelman School of Medicine at Penn and the Philadelphia Veterans Affairs Medical Center and member of the Bioengineering Graduate Group:

D. Kacy Cullen (Image: Eric Sucar)

“To get host Schwann cells all throughout a bioscaffold, you’re basically approximating natural nerve repair,” Cullen says. Indeed, when Le and Cullen’s groups collaborated to implant these grafts into rodents with a facial nerve injury and then tested the results, they saw evidence of a functional repair. The animals had less facial droop than those that received an “empty” graft and nerve conduction was restored. The implanted stem cells also survived in the animals for months following the transplant.

“The animals that received nerve conduits laden with the infused cells had a performance that matched the group that received an autograft for their repair,” he says. “When you’re able to match the performance of the gold-standard procedure without a second surgery to acquire the autograft, that is definitely a technology to pursue further.”

Read the full story and view the full list of collaborators in Penn Today.

Dani Bassett Elected an American Physical Society Fellow

Dani Bassett, Ph.D.

Dani S. Bassett,  J. Peter Skirkanich Professor in the departments of Bioengineering and Electrical and Systems Engineering, has been elected a 2021 Fellow of the American Physical Society (APS) “for significant contributions to the network modeling of the human brain, including dynamical changes caused by evolution, learning, aging, and disease.”

The prestigious APS Fellowship Program signifies recognition by one’s professional peers. Each year, no more than one half of one percent of the APS membership is recognized with this distinct honor. Bassett’s election and groundbreaking work in biological physics and network science will be recognized through presentation of a certificate at the APS March Meeting.

Bassett is a pioneer in the field of network neuroscience, an emerging subfield which incorporates elements of mathematics, physics,  biology and systems engineering to better understand how the overall shape of connections between individual neurons influences cognitive traits. They lead the Complex Systems lab which tackles problems at the intersection of science, engineering, and medicine using systems-level approaches, exploring fields such as curiosity, dynamic networks in neuroscience, and psychiatric disease.

Bassett recently collaborated with Penn artist-in-residence Rebecca Kamen and other scholars on an interdisciplinary art exhibit on the creative process in art and science at the Katzen Art Center at American University. They have also published research modeling different types of curiosity and exploring gender-based citation bias in neuroscience publishing.

“I’m thrilled and humbled to receive this honor from the American Physical Society,” says Bassett. “I am indebted to the many fantastic mentees, colleagues, and mentors that have made my time in science such an exciting adventure. Thank you.”

Read more stories about Bassett’s research here.

Penn Anti-Cancer Engineering Center Will Delve Into the Disease’s Physical Fundamentals

by Evan Lerner

A colorized microscope image of an osteosarcoma shows how cellular fibers can transfer physical force between neighboring nuclei, influencing genes. The Penn Anti-Cancer Engineering Center will study such forces, looking for mechanisms that could lead to new treatments or preventative therapies.

Advances in cell and molecular technologies are revolutionizing the treatment of cancer, with faster detection, targeted therapies and, in some cases, the ability to permanently retrain a patient’s own immune system to destroy malignant cells.

However, there are fundamental forces and associated challenges that determine how cancer grows and spreads. The pathological genes that give rise to tumors are regulated in part by a cell’s microenvironment, meaning that the physical push and pull of neighboring cells play a role alongside the chemical signals passed within and between them.

The Penn Anti-Cancer Engineering Center (PACE) will bring diverse research groups from the School of Engineering and Applied Science together with labs in the School of Arts & Sciences and the Perelman School of Medicine to understand these physical forces, leveraging their insights to develop new types of treatments and preventative therapies.

Supported by a series of grants from the NIH’s National Cancer Institute, the PACE Center is Penn’s new hub within the Physical Sciences in Oncology Network. It will draw upon Penn’s ecosystem of related research, including faculty members from the Abramson Cancer Center, Center for Targeted Therapeutics and Translational Nanomedicine, Center for Soft and Living Matter, Institute for Regenerative Medicine, Institute for Immunology and Center for Genome Integrity.

Dennis Discher and Ravi Radhakrishnan

The Center’s founding members are Dennis Discher, Robert D. Bent Professor with appointments in the Departments of Chemical and Biomolecular Engineering (CBE), Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM), and Ravi Radhakrishnan, Professor and chair of BE with an appointment in CBE.

Discher, an expert in mechanobiology and in delivery of cells and nanoparticles to solid tumors, and Radhakrishnan, an expert on modeling physical forces that influence binding events, have long collaborated within the Physical Sciences in Oncology Network. This large network of physical scientists and engineers focuses on cancer mechanisms and develops new tools and trainee opportunities shared across the U.S. and around the world.

Lukasz Bugaj, Alex Hughes, Jenny Jiang, Bomyi Lim, Jennifer Lukes and Vivek Shenoy (Clockwise from upper left).

Additional Engineering faculty with growing efforts in the new Center include Lukasz Bugaj, Alex Hughes and Jenny Jiang (BE), Bomyi Lim (CBE), Jennifer Lukes (MEAM) and Vivek Shenoy (Materials Science and Engineering).

Among the PACE Center’s initial research efforts are studies of the genetic and immune mechanisms associated with whether a tumor is solid or liquid and investigations into how physical stresses influence cell signaling.

Originally posted in Penn Engineering Today.

With NIH Pioneer Award, Jennifer E. Phillips-Cremins Will Study Genome Folding’s Role in Long-term Memory

by Evan Lerner

Jennifer E. Phillips-Cremins (upper left) and members of her lab.

Each year, the National Institutes of Health (NIH) recognizes exceptionally creative scientists through its High-Risk, High-Reward Research Program. The four awards granted by this program are designed to support researchers whose “out of the box” and “trailblazing” ideas have the potential for broad impact.

Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Penn Engineering’s Department of Bioengineering and the Perelman School of Medicine’s Department of Genetics, is one such researcher. As a recipient of an NIH Director’s Pioneer Award, she will receive $3.5 million over five years to support her work on the role that the physical folding of chromatin plays in the encoding of neural circuit and synapse properties contributing to long-term memory.

Phillips-Cremins’ award is one of 106 grants made through the High-Risk, High-Reward program this year, though she is only one of 10 to receive the Pioneer Award, which is the program’s largest funding opportunity.

“The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known,” said NIH Director Francis S. Collins.

Phillips-Cremins’ research is in the general field of epigenetics, the molecular and structural modifications that allow the genome — an identical copy of which is found in each cell — to express genes differently at different times and in different parts of the body. Within this field, her lab focuses on higher-order folding patterns of the DNA sequence, which bring distant sets of genes and regulatory elements into close proximity with one another as they are compressed inside the cell’s nucleus.

Previous work from the Cremins lab has investigated severe genome misfolding patterns common across a class of genetic neurological disorders, including fragile X syndrome, Huntington’s disease, ALS and Friedreich’s ataxia.

With the support of the Pioneer Award, she and the members of her lab will extend that research to a more fundamental question of neuroscience: how memory is encoded over decades, despite the rapid turnover of the relevant proteins and RNA sequences within the brain’s synapses.

“Our long-term goals are to understand how, when and why pathologic genome misfolding leads to synaptic dysfunction by way of disrupted gene expression,” said Phillips-Cremins, “as well as to engineer the genome’s structure-function relationship to reverse pathologic synaptic defects in debilitating neurological diseases.”

Originally posted in Penn Engineering Today.

BE Seminar: “Phage and Robotics-Assisted Biomolecular Evolution” (Emma Chory)

Emma Chory, Ph.D.

Speaker: Emma Chory, Ph.D.
Postdoctoral Fellow
Sculpting Evolution Laboratory
Massachusetts Institute of Technology

Date: Thursday, October 21, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Room: Moore 216

Abstract: Evolution occurs when selective pressures from the environment shape inherited variation over time. Within the laboratory, evolution is commonly used to engineer proteins and RNA, but experimental constraints have limited our ability to reproducibly and reliably explore key factors such as population diversity, the timing of environmental changes, and chance. We developed a high-throughput system for the analytical exploration of molecular evolution using phage-based mutagenesis to evolve many distinct classes of biomolecules simultaneously. In this talk, I will describe the development of our open-source python:robot integration platform which enables us to adjust the stringency of selection in response to real-time evolving activity measurements and to dissect the historical, environmental, and random factors governing biomolecular evolution. Finally, I will talk about our many on-going projects which utilize this system to evolve previously intractable biomolecules using novel small-molecule substrates to target the undruggable proteome.

Emma Chory Bio: Emma Chory is a postdoctoral fellow in the Sculpting Evolution Group at MIT, advised by Kevin Esvelt and Jim Collins. Emma’s research utilizes directed evolution, robotics, and chemical biology to evolve biosynthetic pathways for the synthesis of novel peptide-based therapeutics. Emma obtained her PhD in Chemical Engineering in the laboratory of Gerald Crabtree at Stanford University. She is the recipient of the NSF Graduate Research Fellowship and a pre- and postdoctoral NIH NRSA Fellowship.

How a Diversity Program Enabled a Childhood Orthopaedics Patient’s Research Dreams

by Julie Wood

As a child, Sonal Mahindroo would go to her orthopaedics appointments with her family, slowly becoming more and more fascinated by the workings and conditions of the musculoskeletal system. While being treated for scoliosis, she would receive children’s books from her doctor that helped provide clear and simplified explanations of orthopaedic topics, which supported her interest.

Nearly a decade later, Mahindroo is still interested in expanding her orthopaedic knowledge, and a Penn Medicine program is helping fuel that expansion. Now a senior at St. Bonaventure University in New York, Mahindroo spends her time at the university’s lab. But in addition to that, this year, she was able to take part in more learning opportunities with Penn Medicine’s support, via the McKay Orthopaedic Research Lab’s Diversity, Equity, and Inclusion (DEI) committee’s conference grant program.

McKay’s DEI committee — consisting of faculty, post-docs, graduate students, and staff — offers a welcoming environment and resources that support people of all identities, empowering them to bring forward unique perspectives to orthopaedic research.

“Our goal is to improve diversity and culture both within McKay and in the orthopaedic research community outside of Penn,” said Sarah Gullbrand, PhD, a research assistant professor at the McKay Lab. “We wanted to provide an opportunity for students to attend a conference and make connections to help them pursue their interest in orthopaedic research.”

The McKay conference grant supports undergraduate students who have been unable to get hands-on research experience. Participants are provided with the opportunity to network with leaders in the field of orthopaedic research, listen to cutting-edge research presentations, and learn about ways to get involved in orthopaedic research themselves.

“When launching the conference grant program earlier this year, I was motivated by my own experience attending a conference as an undergraduate. That experience really increased my interest in attending graduate school and taught me a lot about the breadth of research in orthopaedics,” said Hannah Zlotnick, a PhD student at the McKay Lab and member of the DEI committee. Through the McKay Conference Grants, the committee has supported two cohorts of students. “So far, we’ve been able to fund 11 undergraduate students from around the country to virtually attend orthopaedics conferences and receive early exposure to careers in STEM.”

Along with the conference grant, the McKay Lab holds workshops, book clubs, and other programs focused on DEI-related topics. As part of their efforts for promoting gender diversity in the field, the McKay Lab has previously partnered with the Perry Initiative to offer direct orthopaedic experiences for girls in high school, where they can learn how to suture, and perform mock fracture fixation surgeries on sawbones.

As a primarily male-populated field, orthopaedics could benefit greatly from diversity efforts. While women comprise approximately 50 percent of medical school graduates in the United States, they represent only 14 percent of orthopaedic surgery residents.

“The only women on staff at my orthopaedist’s office were receptionists. There were no female physicians or engineers to make my scoliosis brace,” Mahindroo said. “It was really cool coming to the McKay Lab and seeing how much the field has progressed since then.”

Read more at Penn Medicine News.

N.B. Hannah Zlotnick is a PhD student in Bioengineering studying in the lab of Robert Mauck, Mary Black Ralston Professor in Bioengineering and Orthopaedic Surgery.

Using Big Data to Measure Emotional Well-being in the Wake of George Floyd’s Murder

by Melissa Pappas

George Floyd’s murder had an undeniable emotional impact on people around the world, as evidenced by this memorial mural in Berlin, but quantifying that impact is challenging. Researchers from Penn Engineering and Stanford have used a computational approach on U.S. survey data to break down this emotional toll along racial and geographic lines. Their results show a significantly larger amount of self-reported anger and sadness among Black Americans than their White counterparts. (Photo: Leonhard Lenz)

The murder of George Floyd, an unarmed Black man who was killed by a White police officer, affected the mental well-being of many Americans. The effects were multifaceted as it was an act of police brutality and example of systemic racism that occurred during the uncertainty of a global pandemic, creating an even more complex dynamic and emotional response.

Because poor mental health can lead to a myriad of additional ailments, including poor physical health, inability to hold a job and an overall decrease in quality of life, it is important to understand how certain events affect it. This is especially critical when the emotional burden of these events  falls most on demographics affected by systemic racism. However, unlike physical health, mental health is challenging to characterize and measure, and thus, population-level data on mental health has been limited.

To better understand patterns of mental health on a population scale, Penn Engineers Lyle H. Ungar, Professor of Computer and Information Science (CIS), and Sharath Chandra Guntuku, Research Assistant Professor in CIS, take a computational approach to this challenge. Drawing on large-scale surveys as well as language analysis in social media through their work with the World Well-Being Project, they have developed visualizations of these patterns across the U.S.

Their latest study involves tracking changes in emotional and mental health following George Floyd’s murder. Combining polling data from the U.S. Census and Gallup, Guntuku, Ungar and colleagues have shown that Floyd’s murder spiked a wave of unprecedented sadness and anger across the U.S. population, the largest since relevant data began being recorded in 2009.

Read the full story in Penn Engineering Today.

N.B. Lyle Ungar is also a member of the Penn Bioengineering Graduate Group.

Penn Takes Part in National Science Foundation’s First I-Corps Hubs

by Evan Lerner

A decade ago, the National Science Foundation started its Innovation Corps program to help translate academic research into the wider world. Functioning as a national start-up accelerator, I-Corps provides training and funding to researchers who have a vision for applying their ideas, starting businesses and maximizing social impact. 

Several successful start-ups launched by Penn Engineering students, including Strella BiotechnologyInventXYZ, and Percepta AI have participated in the I-Corps program.

Now, to further develop innovation ecosystems and share regional resources, the NSF has launched a network of five I-Corps Hubs.

Penn is a member of the Mid-Atlantic Hub, which will be led by the University of Maryland at College Park, and include Carnegie Mellon University, George Washington University, Howard University, Johns Hopkins University, North Carolina State University, Penn State, University of North Carolina at Chapel Hill, and Virginia Tech.

The Penn Center for Innovation is currently accepting applications to join the next I-Corps cohort, which begins in October 2021. Teams will receive up to $2,000 to support their start-up, and can apply online.

This story originally appeared in Penn Engineering Today.

N.B.:  Founded by Penn alumna Katherine Sizov (Bio 2019) and winner of a 2019 President’s Innovation Prize, Strella Biotech seeks to reduce food waste through innovative biosensors, and was initially developed in the George H. Stephenson Foundation Educational Laboratory, the bio-makerspace and primary teaching lab of the Department of Bioengineering. Read more BE blog stories featuring Strella Biotechnology.

Atomically-thin, Twisted Graphene Has Unique Properties

by Erica K. Brockmeier

New collaborative research describes how electrons move through two different configurations of bilayer graphene, the atomically-thin form of carbon. These results provide insights that researchers could use to design more powerful and secure quantum computing platforms in the future.

New research published in Physical Review Letters describes how electrons move through two different configurations of bilayer graphene, the atomically-thin form of carbon. This study, the result of a collaboration between Brookhaven National Laboratory, the University of Pennsylvania, the University of New Hampshire, Stony Brook University, and Columbia University, provides insights that researchers could use to design more powerful and secure quantum computing platforms in the future.

“Today’s computer chips are based on our knowledge of how electrons move in semiconductors, specifically silicon,” says first and co-corresponding author Zhongwei Dai, a postdoc at Brookhaven. “But the physical properties of silicon are reaching a physical limit in terms of how small transistors can be made and how many can fit on a chip. If we can understand how electrons move at the small scale of a few nanometers in the reduced dimensions of 2-D materials, we may be able to unlock another way to utilize electrons for quantum information science.”

When a material is designed at these small scales, to the size of a few nanometers, it confines the electrons to a space with dimensions that are the same as its own wavelength, causing the material’s overall electronic and optical properties to change in a process called quantum confinement. In this study, the researchers used graphene to study these confinement effects in both electrons and photons, or particles of light.

The work relied upon two advances developed independently at Penn and Brookhaven. Researchers at Penn, including Zhaoli Gao, a former postdoc in the lab of Charlie Johnson who is now at The Chinese University of Hong Kong, used a unique gradient-alloy growth substrate to grow graphene with three different domain structures: single layer, Bernal stacked bilayer, and twisted bilayer. The graphene material was then transferred onto a special substrate developed at Brookhaven that allowed the researchers to probe both electronic and optical resonances of the system.

“This is a very nice piece of collaborative work,” says Johnson. “It brings together exceptional capabilities from Brookhaven and Penn that allow us to make important measurements and discoveries that none of us could do on our own.”

Read the full story in Penn Today.

Charlie Johnson is the Rebecca W. Bushnell Professor of Physics and Astronomy in the Department of Physics and Astronomy in the School of Arts & Sciences at the University of Pennsylvania and a member of the Penn Bioengineering Graduate Group.

Reimagining Scientific Discovery Through the Lens of an Artist

by Erica K. Brockmeier

Rebecca Kamen, Penn artist-in-residence and visiting scholar, has a new exhibition titled “Reveal: The Art of Reimagining Scientific Discovery” at American University Museum at the Katzen Arts Center that explores curiosity and the creative process across art and science. (Image: Greg Staley)

Rebecca Kamen, Penn artist-in-residence and visiting scholar, has long been interested in science and the natural world. As a Philadelphia native and an artist with a 40-plus-year career, her intersectional work sheds light on the process of scientific discovery and its connections to art, with previous exhibitions that celebrate Apollo 11’s “spirit of exploration and discovery” to new representations of the periodic table of elements.

Now, in her latest exhibition, Kamen has created a series of pieces that highlight how the creative processes in art and science are interconnected. In “Reveal: The Art of Reimagining Scientific Discovery,” Kamen chronicles her own artistic process while providing a space for self-reflection that enables viewers to see the relationship between science, art, and their own creativity.

The exhibit, on display at the Katzen Art Center at American University, was inspired by the work of Penn professor Dani Bassett and American University professor Perry Zurn, the exhibit’s faculty sponsor. The culmination of three years of work, “Reveal” features collaborations with a wide range of scientists, including philosophers at American University, microscopists at the National Institutes of Health studying SARS-CoV-2 , and researchers in Penn’s Complex Systems Lab and the Addiction, Health, and Adolescence (AHA!) Lab.

Continue reading at Penn Today.

Dani S. Bassett is the J. Peter Skirkanich Professor in the departments of Bioengineering and Electrical and Systems Engineering in the School of Engineering and Applied Science at the University of Pennsylvania. She also has appointments in the Department of Physics and Astronomy in Penn’s School of Arts & Sciences and the departments of Neurology and Psychiatry in the Perelman School of Medicine at Penn.

Rebecca Kamen is a visiting scholar and artist-in-residence in the Department of Physics & Astronomy in Penn’s School of Arts & Sciences.

David Lydon-Staley is an assistant professor in the Annenberg School for Communication at Penn and was formerly a postdoc in the Bassett lab.

Dale Zhou is a Ph.D. candidate in Penn’s Neuroscience Graduate Group.

“Reveal: The Art of Reimagining Scientific Discovery,” presented by the Alper Initiative for Washington Art and curated by Sarah Tanguy, is on display at the American University Museum in Washington, D.C., until Dec. 12.

The exhbition catalog, which includes an essay on “Radicle Curiosity” by Perry Zurn and Dani S. Bassett, can be viewed online.