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.

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.

Penn Engineering and CHOP Researchers Identify Nanoparticles that Could Be Used in Therapeutic mRNA Delivery before Birth

by Evan Lerner

William H. Peranteau, Michael J. Mitchell, Margaret Billingsley, Meghana Kashyap, and Rachel Riley (Clockwise from top left)

Researchers at Children’s Hospital of Philadelphia and the School of Engineering and Applied Science at the University of Pennsylvania have identified ionizable lipid nanoparticles that could be used to deliver mRNA as part of fetal therapy. The proof-of-concept study, published today in Science Advances, engineered and screened a number of lipid nanoparticle formulations for targeting mouse fetal organs and has laid the groundwork for testing potential therapies to treat genetic diseases before birth.

“This is an important first step in identifying nonviral mediated approaches for delivering cutting-edge therapies before birth,” said co-senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at CHOP. “These lipid nanoparticles may provide a platform for in utero mRNA delivery, which would be used in therapies like fetal protein replacement and gene editing.”

Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, is the other co-senior author of the study. The co-first authors are Mitchell Lab members Rachel Riley, a postdoctoral fellow, and Margaret Billingsley, a graduate student, and Peranteau Lab member Meghana Kashyap, a research fellow.

Recent advances in DNA sequencing technology and prenatal diagnostics have made it possible to diagnose many genetic diseases before birth. Some of these diseases are treated by protein or enzyme replacement therapies after birth, but by then, some of the damaging effects of the disease have taken hold. Thus, applying therapies while the patient is still in the womb has the potential to be more effective for some conditions. The small fetal size allows for maximal therapeutic dosing, and the immature fetal immune system may be more tolerant of replacement therapy.

Read the full story in Penn Engineering Today.

NB: Rachel Riley is now Assistant Professor in Biomedical Engineering at Rowan University.

Studying ‘Hunters and Busybodies,’ Penn and American University Researchers Measure Different Types of Curiosity

by Melissa Pappas

Knowledge networks were created as participants browsed Wikipedia, where pages became nodes and relatedness between pages became edges. Two diverging styles emerged — “the busybody” and “the hunter.” (Illustrations by Melissa Pappas)

Curiosity has been found to play a role in our learning and emotional well-being, but due to the open-ended nature of how curiosity is actually practiced, measuring it is challenging. Psychological studies have attempted to gauge participants’ curiosity through their engagement in specific activities, such as asking questions, playing trivia games, and gossiping. However, such methods focus on quantifying a person’s curiosity rather than understanding the different ways it can be expressed.

Efforts to better understand what curiosity actually looks like for different people have underappreciated roots in the field of philosophy. Varying styles have been described with loose archetypes, like “hunter” and “busybody” — evocative, but hard to objectively measure when it comes to studying how people collect new information.

A new study led by researchers at the University of Pennsylvania’s School of Engineering and Applied Science, the Annenberg School for Communication, and the Department of Philosophy and Religion at American University, uses Wikipedia browsing as a method for describing curiosity styles. Using a branch of mathematics known as graph theory, their analysis of curiosity opens doors for using it as a tool to improve learning and life satisfaction.

The interdisciplinary study, published in Nature Human Behavior, was undertaken by Danielle Bassett, J. Peter Skirkanich Professor in Penn Engineering’s Departments of Bioengineering and Electrical and Systems Engineering, David Lydon-Staley, then a post-doctoral fellow in her lab, now an assistant professor in the Annenberg School of Communication, two members of Bassett’s Complex Systems Lab, graduate student Dale Zhou and postdoctoral fellow Ann Sizemore Blevins, and Perry Zurn, assistant professor from American University’s Department of Philosophy.

“The reason this paper exists is because of the participation of many people from different fields,” says Lydon-Staley. “Perry has been researching curiosity in novel ways that show the spectrum of curious practice and Dani has been using networks to describe form and function in many different systems. My background in human behavior allowed me to design and conduct a study linking the styles of curiosity to a measurable activity: Wikipedia searches.”

Zurn’s research on how different people express curiosity provided a framework for the study.

Read the full story in Penn Engineering Today.

Bioengineering Faculty Contribute to New Treatment That “Halts Osteoarthritis-Like Knee Cartilage Degeneration”

A recent study published in Science Translational Medicine announces a discovery which could halt cartilage degeneration caused by osteoarthritis: “These researchers showed that they could target a specific protein pathway in mice, put it into overdrive and halt cartilage degeneration over time. Building on that finding, they were able to show that treating mice with surgery-induced knee cartilage degeneration through the same pathway via the state of the art of nanomedicine could dramatically reduce the cartilage degeneration and knee pain.” This development could eventually lead to treating osteoarthritis with injection rather than more complicated surgery.

Among a team of Penn Engineering and Penn Medicine researchers, the study was co-written by Zhiliang Cheng, Research Associate Professor in Bioengineering, Andrew Tsourkas, Professor in Bioengineering, and Ling Qin, Associate Professor of Orthopaedic Surgery in the Perelman School of Medicine and member of the Bioengineering Graduate Group. The lead author was Yulong Wei of the Department of Orthopaedic Surgery and the McKay Orthopaedic Research Laboratory.

Read the press release in Penn Medicine News.

Engineering and Medicine Researchers Collaborate on Studies of Genome Folding in Health and Disease

(Left to right) Top row: Jennifer E. Phillips-Cremins, Rajan Jain, and Eric Joyce. Middle row: Melike Lakadamyali, Golnaz Vahedi, and Gerd Blobel. Bottom row: Bomyi Lim, Arjun Raj, and Stanley Qi.

Popular accounts of the human genome often depict it as a long string of DNA base pairs, but in reality the genome is separated into chromosomes that are tightly twisted and coiled into complex three-dimensional structures. These structures create a myriad of connections between sites on the genome that would be distant from one another if stretched out end-to-end. These “long range interactions” are not incidental — they regulate the activity of our genes during development and can cause disease when disrupted.

Now two teams of researchers at the Perelman School of Medicine at the University of Pennsylvania, each led by Jennifer E. Phillips-Cremins,  associate professor and Dean’s Faculty Fellow in the Department of Bioengineering at the School of Engineering and Applied Science and of Genetics at the Perelman School of Medicine have been awarded grants totaling $9 million from the National Institutes of Health (NIH), as part of a major NIH Common Fund initiative to understand such 3D-genomic interactions.

The initiative, known as the 4D Nucleome Program, broadly aims to map higher-order genome structures across space and time, as well as to understand how the twists and loops of the DNA sequence govern genome function and cellular phenotype in health and disease.

Read the full story in Penn Engineering Today.

N.B.: In addition to Phillips-Cremins, collaborators include Arjun Raj, Professor in Bioengineering and Genetics, and Bioengineering Graduate Group Members Melike Lakadamyali, Associate Professor in Physiology, and Bomyi Lim, Assistant Professor in Chemical and Biomolecular Engineering.

Nader Engheta Awarded Isaac Newton Medal and Prize

 

Nader Engheta, PhD

Nader Engheta, H. Nedwill Ramsey Professor in Electrical and Systems Engineering, Bioengineering and Materials Science and Engineering, has been awarded the 2020 Isaac Newton Medal and Prize by the Institute of Physics (IOP). The IOP is the professional body and scholarly society for physics in the UK and Ireland.

Engheta has been recognized for ” groundbreaking innovation and transformative contributions to electromagnetic complex materials and nanoscale optics, and for pioneering development of the fields of near-zero-index metamaterials, and material-inspired analogue computation and optical nanocircuitry.”

Read the full story in Penn Engineering Today.

Yale Cohen and Douglas Smith Awarded 2020 Penn Medicine Awards of Excellence

Yale Cohen, Ph.D.
Douglas H. Smith, M.D.

The Perelman School of Medicine has announced the winners of the 2020 Penn Medicine Awards of Excellence. The Office of the Dean says:

“These awardees exemplify our profession’s highest values of scholarship, teaching, innovation, commitment to service, leadership, professionalism and dedication to patient care. They epitomize the preeminence and impact we all strive to achieve. The awardees range from those at the beginning of their highly promising careers to those whose distinguished work has spanned decades.

Each recipient was chosen by a committee of distinguished faculty from the Perelman School of Medicine or the University of Pennsylvania. The contributions of these clinicians and scientists exemplify the outstanding quality of patient care, mentoring, research, and teaching of our world-class faculty.”

Two faculty members affiliated with Penn Bioengineering are among this year’s recipients.

Yale Cohen, PhD, Professor of Otorhinolaryngology with secondary appointments in Neuroscience and Bioengineering, is the recipient of the Jane M. Glick Graduate Student Teaching Award. Cohen is an alumnus of the Penn Bioengineering doctoral program and is currently the department’s Graduate Chair.

“Dr. Cohen’s commitment to educating and training the next generation of scientists exemplifies the type of scientist and educator that Jane Glick represented. His students value his highly engaging and supportive approach to teaching, praising his enthusiasm, energy, honesty, and compassion.”

Douglas H. Smith, MD, Robert A. Groff Endowed Professor of Research and Teaching in Neurosurgery and member of the Penn Bioengineering Graduate Group, is the recipient of this year’s William Osler Patient Oriented Research Award:

“Dr. Smith is the foremost authority on diffuse axonal injury (DAI) as the unifying hypothesis behind the short- and long-term consequences of concussion.  After realizing early in his career that concussion, or mild traumatic brain injury (TBI), was a much more serious event than broadly appreciated, Dr. Smith and his team have used computer biomechanical modeling, in vitro and in vivo testing in parallel with seminal human studies to elucidate mechanisms of concussion.”

Read the full story in Penn Medicine Communications.

Ravi Radhakrishnan Adapts Multiscale Modeling Course

 

Ravi Radhakrishnan, PhD

Ravi Radhakrishnan, Professor and Chair of the Department of Bioengineering and Professor in Chemical and Biomolecular Engineering, is among the many faculty who quickly adapted their courses to an online format in the wake of the COVID-19 pandemic. Now, a recent publication in the American Institute of Chemical Engineers (AIChE) Journal reflects one of these revamped courses. The course BE 559: “Multiscale Modeling of Chemical and Biological Systems” provides theoretical, conceptual, and hands-on modeling experience on three different length and time scales: (1) electronic structure (A, ps); (2) molecular mechanics (100A, ns); and (3) deterministic and stochastic approaches for microscale systems (um, sec). During the course, students gained hands-on experience in running codes on real applications together with the following theoretical formalisms: molecular dynamics, Monte Carlo, free energy methods, deterministic and stochastic modeling. The transition to the online format was greatly facilitated by a grant from the Extreme Science and Engineering Discovery Environment (XSEDE) which provided cloud and supercomputing resources to the students facilitating the computational laboratory experience. Radhakrishnan’s article, “A survey of multiscale modeling: Foundations, historical milestones, current status, and future prospects,” reviews the foundations, historical developments, and current paradigms in multiscale modeling (MSM).

Radhakrishnan aspires to modernize computational science, integrating Multiscale Modeling and Data Science for Biological and Biomedical Science & Engineering. His team does so by integrating multiphysics modeling, computing, data science to tackle applications. The integrative approach is pictorially depicted here in terms of modeling different length and timescales using techniques such as molecular dynamics of atomistic systems, Brownian dynamics of coarse-grained systems, and field equations governing continuum scales of macroscopic systems.

Read the full article in the AIChE Journal: https://doi.org/10.1002/aic.17026

Funding source: National Institutes of Health, Grant/Award Number: CA227550

Engineering Bacteria-Killing Molecules from Wasp Venom

César de la Fuente, PhD

César de la Fuente a Presidential Assistant Professor in the Perelman School of Medicine’s departments of Psychiatry and Microbiology and Engineering’s department of Bioengineering, has racked up accolades for his innovative, computational approach to discovering new antibiotics.

Now, in his most recent study, de la Fuente has shown how these vital drugs might be derived from wasp venom.

The study, published in The Proceedings of the National Academy of Sciences, involved altering a highly toxic small protein from a common Asian wasp species, Vespula lewisii, the Korean yellow-jacket wasp. The alterations enhanced the molecule’s ability to kill bacterial cells while greatly reducing its ability to harm human cells. In animal models, de la Fuente and his colleagues showed that this family of new antimicrobial molecules made with these alterations could protect mice from otherwise lethal bacterial infections.

There is an urgent need for new drug treatments for bacterial infections, as many circulating bacterial species have developed a resistance to older drugs. The U.S. Centers for Disease Control & Prevention has estimated that each year nearly three million Americans are infected with antibiotic-resistant microbes and more than 35,000 die of them. Globally the problem is even worse: Sepsis, an often-fatal inflammatory syndrome triggered by extensive bacterial infection, is thought to have accounted for about one in five deaths around the world as recently as 2017.

“New antibiotics are urgently needed to treat the ever-increasing number of drug-resistant infections, and venoms are an untapped source of novel potential drugs. We think that venom-derived molecules such as the ones we engineered in this study are going to be a valuable source of new antibiotics,” says de la Fuente.

De la Fuente and his team started with a small protein, or “peptide,” called mastoparan-L, a key ingredient in the venom of Vespula lewisii wasps. Mastoparan-L-containing venom is usually not dangerous to humans in the small doses delivered by wasp stings, but it is quite toxic. It destroys red blood cells, and triggers a type of allergic/inflammatory reaction that in susceptible individuals can lead to a fatal syndrome called anaphylaxis—in which blood pressure drops and breathing becomes difficult or impossible.

Mastoparan-L (mast-L) also is known for its moderate toxicity to bacterial species, making it a potential starting point for engineering new antibiotics. But there are still some unknowns, including how to enhance its anti-bacterial properties, and how to make it safe for humans.

Continue reading at Penn Medicine News.