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.
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.
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.
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).
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
MatthewAronson 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.
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.”
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.”
Brian Litt, Professor in Bioengineering in Penn Engineering and in Neurology in the Perelman School of Medicine, spoke to Neurology Today about the advances in technology for detecting and forecasting seizures.
The Litt Lab for Translational Neuroengineering translates neuroengineering research directly into patient care, focusing on epilepsy and a variety of research initiatives and clinical applications.
“Dr. Litt’s group is working with one of a number of startups developing ‘dry’ electrode headsets for home EEG monitoring. ‘They are still experimental, but they’re getting better, and I’m really optimistic about the possibilities there.'”
Brain development does not occur uniformly across the brain, but follows a newly identified developmental sequence, according to a new Penn Medicine study. Brain regions that support cognitive, social, and emotional functions appear to remain malleable—or capable of changing, adapting, and remodeling—longer than other brain regions, rendering youth sensitive to socioeconomic environments through adolescence. The findings are published in Nature Neuroscience.
Researchers charted how developmental processes unfold across the human brain from the ages of 8 to 23 years old through magnetic resonance imaging (MRI). The findings indicate a new approach to understanding the order in which individual brain regions show reductions in plasticity during development.
Brain plasticity refers to the capacity for neural circuits—connections and pathways in the brain for thought, emotion, and movement—to change or reorganize in response to internal biological signals or the external environment. While it is generally understood that children have higher brain plasticity than adults, this study provides new insights into where and when reductions in plasticity occur in the brain throughout childhood and adolescence.
The findings reveal that reductions in brain plasticity occur earliest in “sensory-motor” regions, such as visual and auditory regions, and occur later in “associative” regions, such as those involved in higher-order thinking (problem solving and social learning). As a result, brain regions that support executive, social, and emotional functions appear to be particularly malleable and responsive to the environment during early adolescence, as plasticity occurs later in development.
“Studying brain development in the living human brain is challenging. A lot of neuroscientists’ understanding about brain plasticity during development actually comes from studies conducted with rodents. But rodent brains do not have many of what we refer to as the association regions of the human brain, so we know less about how these important areas develop,” says corresponding author Theodore D. Satterthwaite,the McLure Associate Professor of Psychiatry in the Perelman School of Medicine, and director of the Penn Lifespan Informatics and Neuroimaging Center (PennLINC).
The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year, the Department of Bioengineering at the University of Pennsylvania recognizes the stellar work of four graduate students in Bioengineering.
Margaret Billingsley
Dissertation: “Ionizable Lipid Nanoparticles for mRNA CAR T Cell Engineering”
Maggie Billingsley
Margaret earned a bachelor’s degree in Biomedical Engineering from the University of Delaware where she conducted research in the Day Lab on the use of antibody-coated gold nanoparticles for the detection of circulating tumor cells. She conducted doctoral research in the lab of Michael J. Mitchell, J. and Peter Skirkanich Assistant Professor in Bioengineering. After defending her thesis at Penn in 2022, Margaret began postdoctoral training at the Massachusetts Institute of Technology (MIT) in the Hammond Lab where she is investigating the design and application of polymeric nanoparticles for combination therapies in ovarian cancer. She plans to use these experiences to continue a research career focused on drug delivery systems.
“Maggie was an absolutely prolific Ph.D. student in my lab, who pioneered the development of new mRNA lipid nanoparticle technology to engineer the immune system to target and kill tumor cells,” says Mitchell. “Maggie is incredibly well deserving of this honor, and I am so excited to see what she accomplishes next as a Postdoctoral Fellow at MIT and ultimately as a professor running her own independent laboratory at a top academic institution.”
Victoria Muir
Dissertation: “Designing Hyaluronic Acid Granular Hydrogels for Biomaterials Applications”
Victoria Muir
Victoria is currently a Princeton University Presidential Postdoctoral Research Fellow in the lab of Sujit S. Datta, where she studies microbial community behavior in 3D environments. She obtained her Ph.D. in 2022 as an NSF Graduate Research Fellow at Penn Bioengineering under the advisement of Jason A. Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. She received a B.ChE. in Chemical Engineering from the University of Delaware in 2018 as a Eugene DuPont Scholar. Outside of research, Victoria is highly active in volunteer and leadership roles within the American Institute of Chemical Engineers (AIChE), currently serving as Past Chair of the Young Professionals Community and a member of the Career and Education Operating Council (CEOC). Victoria’s career aspiration is to become a professor of chemical engineering and to lead a research program at the interaction of biomaterials, soft matter, and microbiology.
“Victoria was a fantastic Ph.D. student,” says Burdick. “She worked on important projects related to granular materials from the fundamentals to applications in tissue repair. She was also a leader in outreach activities, a great mentor to numerous undergraduates, and is already interviewing towards an independent academic position.”
Sadhana Ravikumar
Dissertation: “Characterizing Medial Temporal Lobe Neurodegeneration Due to Tau Pathology in Alzheimer’s Disease Using Postmortem Imaging”
Sadhana Ravikumar
Sadhana completed her B.S. in Electrical Engineering at the University of Cape Town, South Africa in 2014 and her M.S. in Biomedical Engineering from Carnegie Mellon University in 2017. Outside of the lab, she enjoys spending time in nature and exploring restaurants in Philadelphia with friends. She focused her doctoral work on the development of computational image analysis techniques applied to ex vivo human brain imaging data in the Penn Image Computing and Science Laboratory of Paul Yushkevich, Professor of Radiology at the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group. She hopes to continue working at the intersection of machine learning and biomedical imaging to advance personalized healthcare and drug development.
“Dr. Sadhana Ravikumar’s Ph.D. work is a tour de force that combines novel methodological contributions crafted to address the challenge of anatomical variability in ultra-high resolution ex vivo human brain MRI with new clinical knowledge on the contributions of molecular pathology to neurodegeneration in Alzheimer’s disease,” says Yushkevich. “I am thrilled that this excellent contribution, as well as Sadhana’s professionalism and commitment to mentorship, have been recognized through the Sol Pollack award.”
Hannah Zlotnick
Dissertation: “Remote Force Guided Assembly of Complex Orthopaedic Tissues”
Hannah Zlotnick
Hannah was a Ph.D. candidate in the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and in Bioengineering. She successfully defended her thesis and graduated in August 2022. During her Ph.D., Hannah advanced the state-of-the-art in articular cartilage repair by harnessing remote fields, such as magnetism and gravity. Using these non-invasive forces, she was able to control cell positioning within engineered tissues, similar to the cell patterns within native cartilage, and enhance the integration between cartilage and bone. Her work could be used in many tissue engineering applications to recreate complex tissues and tissue interfaces. Hannah earned a B.S. in Biological Engineering from the Massachusetts Institute of Technology (MIT) in 2017 during which time she was also a member of the women’s varsity soccer team. At Penn, Hannah was also involved in the Graduate Association of Bioengineers (GABE) intramurals & leadership, and helped jumpstart the McKay DEI committee. Since completing her Ph.D., Hannah has begun her postdoctoral research as a Schmidt Science Fellow in Jason Burdick’s lab at the University of Colorado Boulder where she looks to improve in vitro disease models for osteoarthritis.
“Hannah was an outstanding graduate student, embodying all that is amazing about Penn BE – smart, driven, inventive and outstanding in every way,” says Mauck. “ I can’t wait to see where she goes and what she accomplishes!”
Congratulations to our four amazing 2023 Sol Pollack Award winners!
Members of Team Sonura: Tifara Boyce, Gabriela Cano, Gabriella Daltoso, Sophie Ishiwari, & Caroline Magro (credit: Penn BE Labs)
Technical.ly Philly journalist Sarah Huffman recently paid another visit to Penn Bioengineering’s George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, this time for the 2023 Senior Design Expo. Following the annual Senior Design presentations held in the Singh Center for Nanotechnology, in which graduating fourth-year undergraduates in Bioengineering presented their final capstone projects, the Expo offered an opportunity for the teams to do live demonstrations (or demos) for the department’s internal competition judges and the wider BE community.
“In the course of the day, students presented the challenge they were aiming to solve and the technical details of their solution. After, demonstrations sought to find if the devices really worked.
‘[It’s] looking at the device as a whole, because quite frankly, you can say whatever you want at a presentation, does it really work,’ said [BE Labs Director Sevile] Mannickarottu. ‘You can make it look pretty, “but does it work?” is the big question.'”
Daeyeon Lee, Professor and Evan C Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group, is the recipient of two recent honors.
Daeyeon Lee of the School of Engineering and Applied Science delivers the 2023 Thompson Chair Lecture on April 4, 2023. He spoke about reconnecting in the classroom and building community.
“Students who feel connected with instructors and among peers will invest more time, work harder, and retain information better, because they feel comfortable and safe being in the classroom and making space,” Lee said in his opening remarks. “So, there are clearly lots of positive benefits to having this connectedness among students in the classroom.”
Lee’s lecture, titled “(Re)connecting in the Classroom,” was inspired by the “Great Disengagement” referenced in an article published in The Chronicle of Higher Education last year. It portrayed students as more disconnected and uncertain as they re-entered the campus environment.
Read more about Lee’s “(Re)connecting in the Classroom” in Penn Today.
In addition, Lee has received the 2022 Outstanding Achievement Award in Nanoscience from the American Chemical Society (ACS).
The annual award recognizes exceptional achievements in nanoscience research and notable leadership in the area of colloidal nanoparticles and application. Lee was chosen from a large group of extraordinary nominees among the invited speakers, “for pioneering research in development of factory-on-a-chip and its application for large scale nanoparticle synthesis and functionalization.”
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.
