Nanorobotic Systems Presents New Options for Targeting Fungal Infections

by Nathi Magubane

Candida albicans is a species of yeast that is a normal part of the human microbiota but can also cause severe infections that pose a significant global health risk due to their resistance to existing treatments, so much so that the World Health Organization has highlighted this as a priority issue. The picture above shows a before (left) and after (right) fluorescence image of fungal biofilms being precisely targeted by nanozyme microrobots without bonding to or disturbing the tissue sample. (Image: Min Jun Oh and Seokyoung Yoon)

Infections caused by fungi, such as Candida albicans, pose a significant global health risk due to their resistance to existing treatments, so much so that the World Health Organization has highlighted this as a priority issue.

Although nanomaterials show promise as antifungal agents, current iterations lack the potency and specificity needed for quick and targeted treatment, leading to prolonged treatment times and potential off-target effects and drug resistance.

Now, in a groundbreaking development with far-reaching implications for global health, a team of researchers jointly led by Hyun (Michel) Koo of the University of Pennsylvania School of Dental Medicine and Edward Steager of Penn’s School of Engineering and Applied Science has created a microrobotic system capable of rapid, targeted elimination of fungal pathogens.

“Candida forms tenacious biofilm infections that are particularly hard to treat,” Koo says. “Current antifungal therapies lack the potency and specificity required to quickly and effectively eliminate these pathogens, so this collaboration draws from our clinical knowledge and combines Ed’s team and their robotic expertise to offer a new approach.”

The team of researchers is a part of Penn Dental’s Center for Innovation & Precision Dentistry, an initiative that leverages engineering and computational approaches to uncover new knowledge for disease mitigation and advance oral and craniofacial health care innovation.

For this paper, published in Advanced Materials, the researchers capitalized on recent advancements in catalytic nanoparticles, known as nanozymes, and they built miniature robotic systems that could accurately target and quickly destroy fungal cells. They achieved this by using electromagnetic fields to control the shape and movements of these nanozyme microrobots with great precision.

“The methods we use to control the nanoparticles in this study are magnetic, which allows us to direct them to the exact infection location,” Steager says. “We use iron oxide nanoparticles, which have another important property, namely that they’re catalytic.”

Read the full story in Penn Today.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and in the divisions of Pediatric Dentistry and Community Oral Health and is the co-founder of the Center for Innovation & Precision Dentistry in the School of Dental Medicine at the University of Pennsylvania. He is a member of the Penn Bioengineering Graduate Group.

Edward Steager is a research investigator in the School of Engineering and Applied Science’s General Robotics, Automation, Sensing & Perception Laboratory at Penn.

Other authors include Min Jun Oh, Alaa Babeer, Yuan Liu, Zhi Ren, Zhenting Xiang, Yilan Miao, and Chider Chen of Penn Dental; and David P. Cormode and Seokyoung Yoon of the Perelman School of Medicine. Cormode also holds a secondary appointment in Bioengineering.

This research was supported in part by the National Institute for Dental and Craniofacial Research (R01 DE025848, R56 DE029985, R90DE031532 and; the Basic Science Research Program through the National Research Foundation of Korea of the Ministry of Education (NRF-2021R1A6A3A03044553).

Penn Bioengineering Graduate Student on T Cell Therapy Improvements

Image: Courtesy of Penn Medicine News

 Neil Sheppard,  Adjunct Associate Professor of Pathology and Laboratory Medicine in the Perelman School of Medicine, and David Mai, a Bioengineering graduate student in the School of Engineering and Applied Science, explained the findings of their recent study, which offered a potential strategy to improve T cell therapy in solid tumors, to the European biotech news website Labiotech.

Mai is a graduate student in the lab of Carl H. June, the Richard W. Vague Professor in Immunotherapy in Penn Medicine, Director of the Center for Cellular Immunotherapies (CCI) at the Abramson Cancer Center, and member of the Penn Bioengineering Graduate Group.

Read “Immunotherapy in the fight against solid tumors” in Labiotech.

Read more about this collaborative study here.

Class of 2023 Ivy Day

 

Bella Mirro (left) poses with Penn President Liz Magill. (Image: Prestige Portraits)

For 150 years, Ivy Day has been an annual tradition at Penn, with each graduating class installing at least one new plaque and planting a sprig of ivy. On Saturday, May 13, the class of 2023 added to the 200-plus plaques throughout campus with a stone designed by Marah Sanchez, a Class of 2023 student in the School of Nursing, and remarks from Vice Provost for University Life Karu Kozuma.

“The Ivy Day Award Ceremony is a special celebration that gives us an opportunity to acknowledge the contributions and accomplishments of our graduating student leaders,” Kozuma says. “It is also an occasion to create connections. At the ceremony, we have the privilege of meeting family members and loved ones who have supported the students, while the students can connect with alumni who received the same recognition 25 years ago.”

Among the honorees were several Penn Bioengineering students.

Isabella Mirro was presented with the Penn Student Agencies Award by President Liz Magill. This award recognizes distinguished academic achievement and significant leadership in undergraduate activities by a member of the senior class. Mirro, a graduate of the undergraduate Class of 2023, was recently profiled in 34th Street Magazine.

President Liz Magill (right) with the winners of the President’s Innovation Prize. (Image: Prestige Portraits)

Additionally, Tifara Boyce, Gabriela Cano, Gabriella Daltoso, Sophie Ishiwari, and Caroline Magro were formally presented with the President’s Innovation Prize for their startup Sonura. Sonura was featured in Penn Today for their award-winning beanie for NICU infants.

Read the full list of Ivy Day awards in Penn Today.

Folding@Home: How You, and Your Computer, Can Play Scientist

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Greg Bowman kneels, working on a server.
Folding@home is led by Gregory Bowman, a Penn Integrates Knowledge Professor who has appointments in the Departments of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science. (Image: Courtesy of Penn Medicine News)

Two heads are better than one. The ethos behind the scientific research project Folding@home is that same idea, multiplied: 50,000 computers are better than one.

Folding@home is a distributed computing project which is used to simulate protein folding, or how protein molecules assemble themselves into 3-D shapes. Research into protein folding allows scientists to better understand how these molecules function or malfunction inside the human body. Often, mutations in proteins influence the progression of many diseases like Alzheimer’s disease, cancer, and even COVID-19.

Penn is home to both the computer brains and human minds behind the Folding@home project which, with its network, forms the largest supercomputer in the world. All of that computing power continually works together to answer scientific questions such as what areas of specific protein implicated in Parkinson’s disease may be susceptible to medication or other treatment.

Led by Gregory Bowman, a Penn Integrates Knowledge professor of Biochemistry and Biophysics in the Perelman School of Medicine who has joint appointments in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science, Folding@home is open for any individual around the world to participate in and essentially volunteer their computer to join a huge network of computers and do research.

Using the network hub at Penn, Bowman and his team assign experiments to each individual computer which communicates with other computers and feeds info back to Philly. To date, the network is comprised of more than 50,000 computers spread across the world.

“What we do is like drawing a map,” said Bowman, explaining how the networked computers work together in a type of system that experts call Markov state models. “Each computer is like a driver visiting different places and reporting back info on those locations so we can get a sense of the landscape.”

Individuals can participate by signing up and then installing software to their standard personal desktop or laptop. Participants can direct the software to run in the background and limit it to a certain percentage of processing power or have the software run only when the computer is idle.

When the software is at work, it’s conducting unique experiments designed and assigned by Bowman and his team back at Penn. Users can play scientist and watch the results of simulations and monitor the data in real time, or they can simply let their computer do the work while they go about their lives.

Read the full story at Penn Medicine News.

Why is Machine Learning Trending in Medical Research but not in Our Doctor’s Offices?

by Melissa Pappas

Illustration of a robot in a white room with medical equipment.Machine learning (ML) programs computers to learn the way we do – through the continual assessment of data and identification of patterns based on past outcomes. ML can quickly pick out trends in big datasets, operate with little to no human interaction and improve its predictions over time. Due to these abilities, it is rapidly finding its way into medical research.

People with breast cancer may soon be diagnosed through ML faster than through a biopsy. Those suffering from depression might be able to predict mood changes through smart phone recordings of daily activities such as the time they wake up and amount of time they spend exercising. ML may also help paralyzed people regain autonomy using prosthetics controlled by patterns identified in brain scan data. ML research promises these and many other possibilities to help people lead healthier lives.

But while the number of ML studies grow, the actual use of it in doctors’ offices has not expanded much past simple functions such as converting voice to text for notetaking.

The limitations lie in medical research’s small sample sizes and unique datasets. This small data makes it hard for machines to identify meaningful patterns. The more data, the more accuracy in ML diagnoses and predictions. For many diagnostic uses, massive numbers of subjects in the thousands would be needed, but most studies use smaller numbers in the dozens of subjects.

But there are ways to find significant results from small datasets if you know how to manipulate the numbers. Running statistical tests over and over again with different subsets of your data can indicate significance in a dataset that in reality may be just random outliers.

This tactic, known as P-hacking or feature hacking in ML, leads to the creation of predictive models that are too limited to be useful in the real world. What looks good on paper doesn’t translate to a doctor’s ability to diagnose or treat us.

These statistical mistakes, oftentimes done unknowingly, can lead to dangerous conclusions.

To help scientists avoid these mistakes and push ML applications forward, Konrad Kording, Nathan Francis Mossell University Professor with appointments in the Departments of Bioengineering and Computer and Information Science in Penn Engineering and the Department of Neuroscience at Penn’s Perelman School of Medicine, is leading an aspect of a large, NIH-funded program known as CENTER – Creating an Educational Nexus for Training in Experimental Rigor. Kording will lead Penn’s cohort by creating the Community for Rigor which will provide open-access resources on conducting sound science. Members of this inclusive scientific community will be able to engage with ML simulations and discussion-based courses.

“The reason for the lack of ML in real-world scenarios is due to statistical misuse rather than the limitations of the tool itself,” says Kording. “If a study publishes a claim that seems too good to be true, it usually is, and many times we can track that back to their use of statistics.”

Such studies that make their way into peer-reviewed journals contribute to misinformation and mistrust in science and are more common than one might expect.

Read the full story in Penn Engineering Today.

The Potential Futures of Neurotech

Roy Hoshi Hamilton, MD, MS, FAAN, FANA

Brain technology offers all kinds of exciting possibilities — from treating conditions like epilepsy or depression, to simply maximizing brain health. But medical ethicists are concerned about potential dangers and privacy concerns. Roy Hamilton, Professor of Neurology in the Perelman School of Medicine,  Director of the Penn Brain Science, Translation, Innovation, and Modulation (BrainSTIM) Center, and member of the Penn Bioengineering Graduate Group, spoke with WHYY about how brain stimulation is being used.

Listen to “Neurotech and the Growing Battle for Our Brains

Two from Penn Bioengineering Graduate Group Elected to the National Academy of Sciences

Four faculty from the University of Pennsylvania have been elected to the United States National Academy of Sciences (NAS). They are David Brainard of the School of Arts & Sciences; Duncan Watts of the Annenberg School of Communication, School of Engineering and Applied Science, and Wharton School; and Susan R. Weiss and Kenneth S. Zaret of the Perelman School of Medicine.

They join 120 members and 23 international members elected by their peers this year to NAS. Recognized for “distinguished and continuing achievements in original research,” this new class brings the total number of active members to 2,565 and of international members to 526.

Brainard and Zaret are members of the Penn Bioengineering Graduate Group.

David Brainard is the RRL Professor of Psychology, director of the Vision Research Center, and associate dean for the natural sciences in the School of Arts & Sciences. His research focuses on human vision, using both experiments and computer modeling of visual processing, to understand how the visual system deciphers information about objects from light entering the eye. Specifically, he and his lab are interested in color vision, conducting psychophysical experiments to investigate how the appearance of color is affected by an object’s surface properties and ambient light, and how color perception aids in identifying objects. Brainard is the recipient of many honors, including the Macbeth Award from the Inter-Society Color Council, Stein Innovation Award from Research to Prevent Blindness, and Edgard D. Tillyer Award from Optica. He is an elected member of the Society of Experimental Psychologists, a Silver Fellow of the Association for Research in Vision and Ophthalmology, and a Fellow of the Association for Psychological Science.

Kenneth Zaret

Kenneth S. Zaret is the Joseph Leidy Professor in the Department of Cell and Developmental Biology at the Perelman School of Medicine, director of the Institute for Regenerative Medicine, and a member of the Cell and Molecular Biology Graduate Program. His research focuses on gene regulation, cell differentiation, and chromatin structure, with a goal of elucidating these phenomena in the context of embryonic development and tissue regeneration. Pinpointing these aspects of development at the cellular level can serve as the basis for developing future therapeutics and experimental models that further scientists’ ability to understand and cure disease. Zaret has been the recipient of many honors, including a MERIT Award from the National Institutes of Health, the Stanley N. Cohen Biomedical Research Award, and election as a fellow of the American Association for the Advancement of Science.

Read the full announcement in Penn Today.

CiPD Fellows Recognized with Research Awards

Members of the inaugural cohort of fellows in the Center for Innovation and Precision Dentistry (CiPD)’s NIDCR T90/R90 Postdoctoral Training Program have been recognized for their research activities with fellows receiving awards from the American Association for Dental, Oral, and Craniofacial Research (AADOCR), the Society for Biomaterials, and the Osteology Foundation. All four of the honored postdocs are affiliated with Penn Bioengineering.

Zhi Ren

Zhi Ren won first place in the Fives-Taylor Award at the AADOCR Mini Symposium for Young Investigators. A postdoctoral fellow in the labs of Dr. Hyun (Michel) Koo at Penn Dental Medicine (and member of the Penn Bioengineering Graduate Group) and Dr. Kathleen Stebe of Penn Engineering, Dr. Ren’s research focuses on understanding how bacterial and fungal pathogens interact in the oral cavity to form a sticky plaque biofilm on teeth, which gives rise to severe childhood tooth decay that affects millions of children worldwide. In his award-winning study, titled “Interkingdom Assemblages in Saliva Display Group-Level Migratory Surface Mobility”, Dr. Ren discovered that bacteria and fungi naturally present in the saliva of toddlers with severe decay can form superorganisms able to move and rapidly spread on tooth surfaces.

Justin Burrell

Justin Burrell won second place in the AADOCR Hatton Competition postdoctoral category for his research. Dr. Burrell has been working with Dr. Anh Le in Penn Dental Medicine’s Department of Oral Surgery/Pharmacology and Dr. D. Kacy Cullen of Penn Medicine and Penn Bioengineering. Together, their interdisciplinary team of clinician-scientists, biologists, and neuroengineers have been developing novel therapies to expedite facial nerve regeneration and increase meaningful functional recovery.

Marshall Padilla

Marshall Padilla earned third place at the Society for Biomaterials Postdoctoral Recognition Award Competition for a project titled, “Branched lipid architecture improves lipid-nanoparticle-based mRNA delivery to the liver via enhanced endosomal escape”. Padilla was also a finalist in the AADOCR Hatton Award Competition, presenting on a separate project titled, “Lipid Nanoparticle Optimization for mRNA-based Oral Cancer Therapy”. Both projects employ lipid nanoparticles, the same delivery vehicles used in the mRNA COVID-19 vaccine technology. A postdoctoral fellow in the lab of Dr. Michael J. Mitchell of Penn’s Department of Bioengineering, Dr. Padilla’s research focuses on developing new ways to enhance the efficacy and safety of lipid nanoparticle technology and its applications in dentistry and biomedicine. He has been working in collaboration with Dr. Shuying (Sheri) Yang and Dr. Anh Le in Penn Dental Medicine.

Dennis Sourvanos

Dennis Sourvanos (GD’23, DScD’23) was the recipient of the Trainee Travel Grant award through the Osteology Foundation (Lucerne Switzerland). Dr. Sourvanos will be presenting his research related to medical dosimetry and tissue regeneration at the International Osteology Symposium in Barcelona, Spain (April 27th – 29th 2023). He also presented at the 2023 AADOCR/CADR Annual Meeting for his project titled, “Validating Head-and-Neck Human-Tissue Optical Properties for Photobiomodulation and Photodynamic Therapies.” Dr. Sourvanos has been working with Dr. Joseph Fiorellini in Penn Dental Medicine’s Department of Periodontics and Dr. Timothy Zhu in the Hospital of the University of Pennsylvania’s Department of Radiation Oncology and the Smilow Center for Translational Research (and member of the Penn Bioengineering Graduate Group).

Read the full announcement in Penn Dental Medicine News.

More 2023 SFB STAR Awards for Penn Bioengineering Students

Following up on our recent announcement of two Student Travel Achievement Recognition (STAR) Awards from the Society for Biomaterials (SFB) for members of the lab of Mike Mitchell, we are pleased to announce that two more Penn Bioengineering students also received STAR Awards!

Matthew Aronson and Alexandra Dumas are both members of the lab of Riccardo Gottardi, Assistant Professor in Pediatrics in the Perelman School of Medicine and in Bioengineering in the School of Engineering and Applied Science. Both presented their work at the recent 2023 SFB Annual Meeting and Exposition in San Diego, California in April 2023 and were honored with STAR Awards for their research.

The Gottardi Bioengineering and Biomaterials Laboratory studies treatment and function restoration for children with otolaryngologic disorders through the Children’s Hospital of Philadelphia  (CHOP) in the Division of Otolaryngology.

Matthew Aronson

Matthew Aronson is a third-year Ph.D. student in Bioengineering, an Ashton Fellow, and a NSF Fellow. His doctoral research focuses on studying pediatric airway diseases and disorders. More specifically, he is interested in how bacteria of the upper airway are responsible for the development and progression the disease subglottic stenosis, narrowing of the airway. In addition to understanding this devastating disease in the context of pediatric patients at CHOP, he also designed a novel drug-eluting endotracheal tube to deliver a selective antimicrobial peptide to function as a treatment modality for the prevention of the disease.

Alexandra Dumas

Alexandra Dumas is a rising fourth-year undergraduate in Bioengineering from Durban, South Africa. She is a PURM Fellow and a University Scholar. Her recent work in the Gottardi Lab focuses on using decellularized cartilage scaffolds to repair the meniscus and airway. After her undergraduate degree, she hopes to pursue a Ph.D. or M.D.-Ph.D. in bioengineering to pursue the design of new biomaterials for low-resource communities.

 

Read more stories featuring Gottardi and his team here.

Safe and Sound: Sonura Supports Newborn Development by Sequestering Disruptive Noise

by Nathi Magubane

Recipients of the 2023 President’s Innovation Prize, team Sonura, five bioengineering graduates from the School of Engineering and Applied Science, have created a device that filters out disruptive environmental noises for infants in neonatal intensive care units. Their beanie offers protection and fosters parental connection to newborns while also supporting their development.

Machines beeping and whirring in a rhythmic chorus, the droning hum of medical equipment, and the bustles of busy health care providers are the familiar sounds of an extended stay at a hospital. This cacophony can create a sense of urgency for medical professionals as they move about with focused determination, closely monitoring their patients, but for infants in neonatal intensive care units (NICU) this constant noise can be overwhelming and developmentally detrimental.

Enter Tifara Boyce, from New York City; Gabriela Cano, from Lawrenceville, New Jersey; Gabriella Daltoso, from Boise, Idaho; Sophie Ishiwari, from Chicago, and Caroline Magro, from Alexandria, Virginia, bioengineering graduates from the School of Engineering and Applied Science, who have created the Sonura Beanie. Their device filters out harmful noises for NICU infants while supporting cognitive and socioemotional development by allowing parents to send voice messages to their newborns.

The Sonura team members are recipients of the 2023 President’s Innovation Prize, which includes an award of $100,000 and an additional $50,000 living stipend per team member. The recent graduates will spend the year developing their product.

“The Penn engineers behind Sonura are determined to make a difference in the world,” says President Liz Magill. “They identified a substantial medical challenge that affects many parents and their newborn children. With the guidance of their mentors, they are taking key steps to address it and in doing so are improving the developmental prospects for children in the NICU. I am proud the University is able to support their important work.”

The Sonura Beanie’s creation began in the Stephenson Foundation Educational Laboratory and Bio-MakerSpace as a part of the Bioengineering Senior Design class project.

Prototype of the Sonura Beanie. (Image: Courtesy of the Sonura team)

She was particularly struck by the noisiness of the environment and considered the neurodevelopmental outcomes that may arise following long-term exposure to the harsh sounds at a critical developmental stage for infants. This concern prompted Magro to consult her team about potential solutions.

“I was really eager to tackle this problem because it bears some personal significance to me,” says Cano, who works on the device’s mobile application. “My sister was a NICU baby who was two months premature, so, when Caroline and I started talking about the issues a disruptive environment could cause, it seemed like the pieces of a puzzle started to come together.”

Read the full story in Penn Today.