In a paper recently published in Biochemistry, a group of University of Pennsylvania Bioengineering students describe the results of their work designing a new, open-source, low-cost microplate reader. Plate readers are instruments designed to measure light absorption and fluorescence emission from molecules useful for clinical biomarker analyses and assays in a diverse array of fields including synthetic biology, optogenetics, and photosensory biology. This new design costs less than $3500, a significantly lower price than other commercially available alternatives. As described in the paper’s abstract, this design is the latest in a growing trend of open-source hardware to enhance access to equipment for biology labs. The project originated as part of the annual International Genetically Engineering Machine Competition (iGEM), an annual worldwide competition focusing on “push[ing] the boundaries of synthetic biology by tackling everyday issues facing the world” (iGEM website).
The group consists of current junior Andrew Clark (BSE ’20) and recent graduates Karol Szymula (BSE ’18), who works in the lab of Dr. Danielle Bassett, and Michael Patterson (BSE ’18), a Master’s student in Bioengineering and Engineer of Instructional Laboratories. Assistant Professor of Bioengineering Dr. Brian Chow served as their faculty mentor alongside Director of Instructional Labs Sevile Mannickarottu and Michael Magaraci, a Ph.D. candidate in Bioengineering, all of whom serve as co-authors on the published article. The research and design of the project was conducted in the Stephenson Foundation Bioengineering Educational Laboratory here at the University of Pennsylvania’s Department of Bioengineering.
On January 8, 2019 the Department of Bioengineering at Penn held its annual Graduate Group Research Symposium to great success.
Thank you to everyone who attended and participated, our student volunteers, our faculty who participated as judges for the student talks and poster competition, and especially to our keynote speaker, Dr. Sujata Bhatia, Professor of Chemical and Biomolecular Engineering at the University of Delaware.
Congratulations to the award winners:
Student Talks:
First prize – Meagan Ita
Second prize – Nicolette Driscoll
Third prize – Minna Chen
Poster Presentations:
First prize – Mariia Alibekova
Second prize – Jonathan Galarraga, Sonia Kartha, and John Viola
Third prize – Andrei Georgescu
First prize winner Meagan Ita delivers her talk.
We had a great turnout!
John Viola’s group won second prize in the poster competition.
First prize winner Mariia Alibekova discusses her poster.
Mi Yi Kwon with her poster.
Keynote speaker Dr. Sujata Bhatia with Penn BE’s Dr. Daniel Hammer.
The annual Bioengineering Graduate Symposium provides an opportunity for current bioengineering graduate students to showcase their research to faculty and peers through poster sessions and short talks.
Date: January 8th
Location: Wu & Chen Auditorium and Levine Hall Lobby
Time: Check-in opens 12:45, event starts 1 pm.
Keynote Speaker: Dr. Sujata Bhatia,
Professor of Chemical and Bimolecular Engineering, faculty director, McNair Scholars Program,
University of Delaware
“Bioengineering to Alleviate the Global Burden of Disease”
Biochemical and biomedical engineers face an unprecedented opportunity to improve and save the lives of millions worldwide. Both high-income and low-income countries are experiencing an explosion in the incidence of chronic diseases, including coronary artery disease, stroke, diabetes, and cancer. At the same time, low-income countries continue to be plagued by infectious diseases, including HIV, tuberculosis, diarrheal disease, and pneumonia; low-income countries are often said to experience a dual burden of chronic and infectious diseases. Innovative biomedical materials will only reach the clinic if these technologies solve pressing clinical problems. This talk will describe opportunities for bioengineers to alleviate the global burden of disease. The talk will additionally highlight specific examples of unmet clinical needs. Bioengineers in industry, academia, and government can all make a difference, not only by designing novel biomedical products, but also by training the next generation of bioengineers and shaping the future direction of research and development.
Michael Mitchell, PhD, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering at Penn, has been honored with a Rising Star Award in Cellular and Molecular Bioengineering from the Biomedical Engineering Society (BMES). According to the BMES website, “The BMES Cellular and Molecular Bioengineering Special Interest Group brings together researchers with diverse scientific and clinical interests with a common goal of understanding and engineering molecules, cells, their interactions and microenvironments in the pursuit of controlling biological processes and improving the practice of medicine.” Dr. Mitchell received the award and delivered a lecture at the 2019 Cellular and Molecular Bioengineering Conference in San Diego, California in January, 2019.
One of six early-stage investigators from across the nation to receive the honor, Dr. Mitchell was recognized for his work on engineering delivery technologies for cancer gene therapy and immunotherapy, which is helping to lay the foundation for a new class of therapeutic strategies against hematologic cancers such as multiple myeloma and leukemia. In 2018, Dr. Mitchell was awarded the NIH Director’s New Innovator Award for this research, and received the Burroughs Wellcome Fund Career Award at the Scientific Interface) in 2016. He joined the Penn faculty in January 2018 after completing an NIH NCI postdoctoral fellowship with Dr. Robert Langer at the Koch Institute for Integrative Cancer Research at MIT.
The BE Seminar Series continues this week. We hope to see you there!
Speaker: Alison Pouch, Ph.D.
Research Associate, Penn Image Computing & Science Lab, Department of Radiology
Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania
Date: November 29, 2018
Time: 12:00 pm
Location: Room 337, Towne Building
“Shaping Innovation in Heart Valve Surgery with Image-Based Modeling”
A number of challenging questions routinely arise before heart valve surgery. Should a regurgitant valve be repaired or replaced? If repaired, which techniques and maneuvers should be employed? When is the optimal time to perform surgery? This is just the beginning of a series of questions whose answers rely on an individualized assessment of heart valve morphology and function. With advanced imaging technology like 3D echocardiography already in the operating room, we have a window into patient-specific disease characteristics that cannot otherwise be appreciated immediately before surgery. Unfortunately, imaging resources are often not tapped to their full potential, which contributes to delays in surgical innovation. This presentation introduces an image-based modeling approach to creating enhanced visualizations and quantification of heart valves from real-time 3D echocardiography. The goal of this approach is to fundamentally change the way that surgeons interact with and utilize images in the operating room. Pre-operative image-based heart valve models can be used to characterize mechanisms of disease prior to cardiopulmonary bypass and to identify connections between pre-operative image features and clinical outcomes. Image-based modeling provides a means for surgeons to innovate and master new surgical techniques like bicuspid aortic valve repair and to devise new standardized approaches for surgical treatment of ischemic mitral regurgitation. Image analysis and surgical innovation are linked within and beyond the cardiovascular domain, and this work aims to optimize the potential of imaging and shape modeling for pre-surgical planning.
Scientific claims are a foundation of scientific discourse. Extracting claims from scientific articles is primarily done by researchers during literature review and discussions. The enormous growth in scientific articles makes this ever more challenging and time-consuming. Here, we develop a deep neural network architecture to solve the problem. Our model an F1 score of 0.704 on a large corpus of expertly annotated claims within abstracts. Our results suggest that we can use a small dataset of annotated resources to achieve high-accuracy claim detection. We release a tool for discourse and claim detection, and a novel dataset annotated by experts. We discuss further applications beyond Biomedical literature.
Multiple Sclerosis Lesion Segmentation with Joint Label Fusion Evaluated on OASIS and CNN
Scientific claims are a foundation of scientific discourse. Extracting claims from scientific articles is primarily done by researchers during literature review and discussions. The enormous growth in scientific articles makes this ever more challenging and time-consuming. Here, we develop a deep neural network architecture to solve the problem. Our model an F1 score of 0.704 on a large corpus of expertly annotated claims within abstracts. Our results suggest that we can use a small dataset of annotated resources to achieve high-accuracy claim detection. We release a tool for discourse and claim detection, and a novel dataset annotated by experts. We discuss further applications beyond Biomedical literature.
Michael Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, is drawing on a variety of fields — biomaterials engineering, data science, gene therapy and machine learning — to tailor the next generation of drug delivery vehicles with this level of precision.
His work in this field has earned him a $2.4 million NIH Director’s New Innovator Award, which is part of the NIH Common Fund’s High-Risk, High-Reward Research program. The High-Risk, High-Reward Research program supports innovative research proposals that might not prove successful in the conventional peer-review process despite their potential to advance medicine.
The BE Seminar Series continues next week with three lectures delivered by our current PhD Students. We hope to see you there!
“Magnetic Susceptibility of Hemorrhagic Myocardial Infarction”
Brianna Moon, PhD Candidate
Speaker: Brianna Moon, PhD Candidate
Research Advisor: Walter Witschey, PhD
Date: Thursday, September 20, 2018
Time: 12:05pm-12:25pm
Location: Room 337 Towne Building
Abstract:
Hemorrhagic myocardial infarction (MI) has been reported in 41% and 54% of ST-elevated MI patients after primary percutaneous coronary intervention. These patients are at high risk for adverse left ventricle (LV) remodeling, impaired LV function and increased risk of fatal arrhythmias. Relaxation time MRI such as T2*-maps are sensitive to hemorrhagic infarct iron content, but are also affected by myocardial edema and fibrosis. Quantitative Susceptibility Mapping (QSM), which uses the MR signal phase to quantify tissue magnetic susceptibility, may be a more specific and sensitive marker of hemorrhagic MI. The objective of this study was to develop and validate cardiac QSM in a large animal model of myocardial infarction, investigate the association of magnetic susceptibility with iron content and infarct pathophysiology, and compare QSM to relaxation time mapping, susceptibility-weighted imaging (SWI), and late-gadolinium enhanced (LGE) MRI.
“Role of ACTG2 Mutations in Visceral Myopathy”
Sohaib Hashmi, MD/PhD Student
Speaker: Sohaib Hashmi, MD/PhD Student
Research Advisor: Robert O. Heuckeroth, MD, PhD
Date: Thursday, September 20, 2018
Time: 12:30-12:50pm
Location: Room 337 Towne Building
Abstract:
Visceral myopathy is a debilitating chronic medical condition in which smooth muscle of the bowel, bladder, and uterus is weak or dysfunctional. When the bowel muscle is weak and unable to efficiently contract, the bowel becomes distended which causes pain, bilious vomiting, growth failure, and nutritional deficiencies. The abdominal distension can become life-threatening. Patients often become dependent on intravenous nutrition and undergo multiple rounds of abdominal surgery, which only partially alleviates symptoms. Recently, rare mutations in gamma smooth muscle actin (ACTG2) have been shown to be responsible for a large subset of visceral myopathies. ACTG2 is a critical protein in the smooth muscle contractile apparatus. However, we have only limited knowledge of how ACTG2 mutations may cause human disease. To improve our understanding of the pathophysiology of ACTG2 mutations, my work has the following specific aims:
1)Determine how pathogenic ACTG2 mutations affect actin structure and function in primary human intestinal smooth muscle cells (HISMCs).
2) Examine the effects of ACTG2 mutations on differentiation of human pluripotent stem cells into smooth muscle cells (SMCs).
These studies will allow us to elucidate the mechanisms through which ACTG2 mutations impair normal visceral smooth muscle development and function. I am examining the effects of ACTG2 mutations on actin filament organization in fixed cells and actin dynamics in live cells using fluorescent probes. I will investigate changes in contractile force generation using traction force microscopy. I am also developing a novel differentiation method to convert pluripotent stem cells into cells closely resembling visceral SMCs. We will use this method with CRISPR/Cas9 gene editing to study the effects of the mutations on SMC differentiation. We are currently generating pluripotent stem cell lines containing ACTG2 mutations and performing assays to investigate actin organization and dynamics. We are using these systems to identify robust phenotypes highlighting the mechanisms through which ACTG2 mutations cause disease. We hope to leverage this information in the selection of targets for high-throughput drug screening, which may eventually lead to novel treatment strategies for visceral myopathies.
“Distinct Patterns of Longitudinal Cortical Thinking and Perfusion in Pathological Subtypes of Behavioral Variant Frontotemporal Degeneration”
Christopher Olm, PhD Student
Speaker: Christopher Olm, PhD Student
Research Advisor: Murray Grossman, MD, EdD
Date: Thursday, September 20, 2018
Time: 12:55-1:15pm
Location: Room 337 Towne Building
Abstract:
Two main sources of pathology have been identified in the behavioral variant of frontotemporal dementia (bvFTD): tau inclusions (FTLD-tau) and TDP-43 aggregates (FTLD-TDP). With therapies emerging that target these proteins, exploring distinct trajectories of degeneration can be extremely helpful for tracking progression in clinical trials and improve prognosis estimation. We hypothesized that longitudinal cortical thinning (CT) would identify areas of extant disease progression in bvFTD subgroups and longitudinal hypoperfusion would identify distinct regions of anticipated neurodegeneration. We included N=47 patients with probable or definite bvFTD and two MRI scanning sessions including T1-weighted and arterial spin labeling (ASL) scans, recruited through the Penn Frontotemporal Degeneration Center. Neuropathology, genetic mutations, or CSF protein markers (phosphorylated tau (p-tau)/Ab1-42<.09 for likely FTLD; p-tau<8.75 for FTLD-TDP) were used to identify bvFTD with likely FTLD-tau (n=28, mean age=63.1 years, mean disease duration=3.89 years) or likely FTLD-TDP (n=19, mean age=61.9, mean disease duration=3.06). Voxel-wise cortical thickness and cerebral blood flow estimates were generated for each T1 and ASL scan, respectively, using longitudinal pipelines in ANTs. We created annual change images by subtracting follow-up images from baseline and dividing by inter-scan interval. In whole brain voxel-wise comparisons, FTLD-tau showed significantly greater right orbitofrontal CT and longitudinal hypoperfusion in right middle temporal and angular cortex relative to FTLD-TDP. FTLD-TDP displayed greater progressive CT in left superior and middle frontal cortex, precentral gyrus, and right temporal cortex, and longitudinal hypoperfusion in medial prefrontal cortex relative to FTLD-tau. In conclusion, FTLD-tau and FTLD-TDP show distinct patterns of longitudinal CT and hypoperfusion. Structural and functional MRI contribute independent information potentially useful for characterizing disease progression in vivo for clinical trials.
Please join us for the first of our seminar lectures this year!
Rosalind Picard, ScD, FIEEE
Director of Affective Computing Research
Faculty Chair, MIT Mind+Hand+Heart
MIT Media Lab
“What Can We Discover About Emotions and the Brain from Noninvasive Measures?”
Date: Thursday, September 13, 2018
Time: 12:00PM-1:00 PM
Location: 337 Towne Building
Abstract:
Years ago, our team at MIT created wearable as well as non-contact imaging technology and machine learning algorithms to detect changes in human emotion. As we shrunk the sensors and made them able to comfortably collect data 24/7, we started to discover several surprising findings, such as that autonomic activity measured through a sweat response was more specific than 100 years of studies had assumed. While we originally thought this signal of “arousal” or “stress” was quite generally related to overall activation, we learned it could peak even when a patient’s EEG showed a lack of cortical brain activity. This talk will highlight some of the most surprising findings along the journey of measuring emotion “in the wild”with implications for anxiety, depression, sleep-memory consolidation, epilepsy, autism, pain studies, and more. What is the grand challenge we aim to solve next?
Bio:
Rosalind Picard, ScD, FIEEE, is founder and director of the Affective Computing Research Group at the MIT Media Laboratory, co-founder and Chief Scientist of Empatica, improving lives with clinical quality wearable sensors and analytics, and co-founder of Affectiva, providing tools for Emotion AI. Picard is the author of over two hundred fifty peer-reviewed scientific articles and of the book, Affective Computing, which helped launch that field. Picard’s lab at MIT develops technologies to better measure, understand, forecast, and regulate emotion, including personalized machine-learning analytics that work with wearables and your smartphone.
A new approach uses “mechanoceuticals” to treat pain.
Drugs are commonly injected directly into an injury site to speed healing. For chronic pain, clinicians can inject drugs to reduce inflammation in painful joints, or can inject nerve blockers to block the nerve signals that cause pain. In a recent study, a group from UCLA developed a technique to deform a material surrounding nerve fibers to trigger a response in the fibers that would relieve pain. The combination of mechanics and treatment – i.e., ‘mechanoceuticals’ – is a clever way to trick fibers and reverse painful symptoms. Done without any injections and simply controlling magnetic fields outside the body, this approach can be reused as necessary.
The design of this mechanoceutical was completed by Dino Di Carlo, PhD, Professor of Bioengineering, and his team at UCLA’s Sameuli School of Engineering. By encasing tiny, magnetic nanoparticles within a biocompatible hydrogel, the group used magnetic force to stimulate nerve fibers and cause a corresponding decrease in pain signals. This promising development opens up a new approach to pain management, one which can be created with different biomaterials to suit different conditions, and delivered “on demand” without worrying about injections or, for that matter, any prescription drugs.
Understanding the Adolescent Brain
It’s no surprise that adults and adolescents often struggle to understand one another, but the work of neurologists and other researchers provides a possible physical reason for why that might be. Magnetic resonance elastrography (MRE) is a tool used in biomedical imaging to estimate the mechanical properties, or stiffness, of tissue throughout the body. Unexpectedly, a recent study suggests that brain stiffness correlates with cognitive ability, suggesting MRE may provide insight into patients’ behavior, psychology, and psychiatric state.
A new paper in Developmental Cognitive Neuroscience published the results of a study using MRE to track the relative “stiffness” vs. “softness” of adult and adolescent brains. The University of Delaware team, led by Biomedical Engineering Assistant Professor Curtis Johnson, PhD, and his doctoral student Grace McIlvain, sampled 40 living subjects (aged 12-14) and compared the properties to healthy adult brains.
The study found that children and adolescent brains are softer than those of adults, correlating to the overall malleability of childhood development. The team hopes to continue their studies with younger and older children, looking to demonstrate exactly when and how the change from softness to stiffness takes place, and how these properties correspond to individual qualities such as risk-taking or the onset of puberty. Eventually, establishing a larger database of measurements in the pediatric brain will help further studies into neurological and cognitive disorders in children, helping to understand conditions such as multiple sclerosis, autism, and cerebral palsy.
Can Nanoparticles Replace Stents?
Researchers and clinicians have made amazing advances in heart surgery. Stents, in particular, have become quite sophisticated: they are used to both prop open clogged arteries as well as deliver blood-thinning medication slowly over days to weeks in the area of the stent. However, the risk of blood clotting increases with stents and the blood vessels can constrict over time after the stent is placed in the vessel.
A recent NIH grant will support the design of a stent-free solution to unclog blood vessels. Led by Shaoqin Gong, PhD, Vilas Distinguished Professor of Biomedical Engineering at UW-Madison, the team used nanoparticles (or nanoclusters) to directly target the affected blood vessels and prevent regrowth of the cells post-surgery, eliminating the need for a stent to keep the pathways open. These nanoclusters are injected through an intravenous line, further reducing the risks introduced by the presence of the stent. As heart disease affects millions of people worldwide, this new material has far-reaching consequences. Their study is published in the September edition of Biomaterials.
NIST Grant Supports
The National Institute of Standards and Technology (NIST) awarded a $30 million grant to Johns Hopkins University, Binghamton University, and Morgan State University as part of their Professional Research Experience Program (PREP). Over five years, this award will support the collaboration of academics from all levels (faculty, postdoc, graduate, and undergraduate) across the three universities, enabling them to conduct research and attend NIST conferences.
The principal investigator for Binghamton U. is Professor and Chair of the Biomedical Engineering Department, Kaiming Ye, PhD. Dr. Ye is also the Director of the Center of Biomanufacturing for Regenerative Medicine (CBRM), which will participate in this collaborative new enterprise. Dr. Ye hopes that this grant will create opportunities for academics and researchers to network with each other as well as to more precisely define the standards for the fields of regenerative medicine and biomaterial manufacturing.
The gift honors the late A. James Clark, former CEO of Clark Enterprises and Clark Construction Group LLC, one of the country’s largest privately-held general building contractors. It is designed to prepare future engineering and business leaders, with an emphasis on low income families and first-generation college students. Clark never forgot that his business successes began with an engineering scholarship. This has guided the Clark family’s longstanding investments in engineering education and reflects its commitment to ensure college remains accessible and affordable to high-potential students with financial need.
We are proud to say that three incoming Clark Scholars from the Freshman Class of 2022 will be part of the Bioengineering Department here at Penn.
And finally, our congratulations to the new Dean of the School of Engineering at the University of Mississippi: David A. Puleo, PhD. Dr. Puleo earned his bachelor’s degree and doctorate in Biomedical Engineering from Rensselaer Polytechnic Institute. Most recently he served as Professor of Biomedical Engineering and Associate Dean for Research and Graduate Studies at the University of Kentucky’s College of Engineering. Building on his research in regenerative biomaterials, he also founded Regenera Materials, LLC in 2014. Over the course of his career so far, Dr. Puleo received multiple teaching awards and oversaw much departmental growth within his previous institution, and looks poised to do the same for “Ole Miss.”
Michael Mitchell
Speaker: Alison Pouch, Ph.D.
Scientific claims are a foundation of scientific discourse. Extracting claims from scientific articles is primarily done by researchers during literature review and discussions. The enormous growth in scientific articles makes this ever more challenging and time-consuming. Here, we develop a deep neural network architecture to solve the problem. Our model an F1 score of 0.704 on a large corpus of expertly annotated claims within abstracts. Our results suggest that we can use a small dataset of annotated resources to achieve high-accuracy claim detection. We release a tool for discourse and claim detection, and a novel dataset annotated by experts. We discuss further applications beyond Biomedical literature.
Scientific claims are a foundation of scientific discourse. Extracting claims from scientific articles is primarily done by researchers during literature review and discussions. The enormous growth in scientific articles makes this ever more challenging and time-consuming. Here, we develop a deep neural network architecture to solve the problem. Our model an F1 score of 0.704 on a large corpus of expertly annotated claims within abstracts. Our results suggest that we can use a small dataset of annotated resources to achieve high-accuracy claim detection. We release a tool for discourse and claim detection, and a novel dataset annotated by experts. We discuss further applications beyond Biomedical literature.
