Week in BioE (February 13, 2019)

Bioengineers Tackle Heart Disease

Heart disease is currently the leading cause of death in the United States, resulting in about 630,000 deaths every year according to the Center for Disease Control. One of the most common side effects of heart disease is damage to blood vessels and cardiac tissue, which can ultimately lead to conditions like high blood pressure, arrhythmia, and even cardiac arrest. In serious cases of irreversible heart damage, often the only option for patients is a full heart transplant, and efforts to engineer vascularized cardiac tissue grafts have proved challenging in research so far.

But researchers Ying Zheng, Ph.D., and Charles Murry, M.D., Ph.D., both of whom have joint appointments in Bioengineering at the University of Washington, have found success in using human microvascular grafts to create working blood vessels in vitro to treat infarcted rat hearts. The new heart muscle, developed from human embryonic stem cell-derived endothelial cells in petri dishes, was grown with a focus on not only being able to easily integrate it in vivo, but also in creating a patch of vasculature that closely mirrored that of the heart. In concentrating more on the mechanical aspects of the blood vessel network, Zheng and Murry were able to better restore normal blood flow to the damaged rat hearts after integration of the grafts. The study appears in a recent edition of Nature Communications.

Another team of bioengineers, led by Michael Sacks, Ph.D. at the University of Texas at Austin, recently invented a software-based method for repairing mitral valves in the heart. Their work, published in the International Journal for Numerical Methods in Biomedical Engineering, uses computational modeling techniques to create a noninvasive way of simulating repairs to the mitral valve, which will allow for a better prediction of surgical procedures and postoperative side effects on a more patient-specific basis. This ability to know which treatment plan may be best-suited for a given patient is important especially for valve repair, as heart valves are notoriously difficult to model or image due to the complexity of their functions. But through the use of advanced technology in 3D echocardiography, Sacks and his team say that their new model is accurate enough to rely on in clinical settings.

Virtual Reality Assists in the Evaluation of Surgery

Any form of surgery is always a high risk procedure, as it is subject to a wide variety of sources of human error and irregularity, even with the best surgeons. Certainly, there should be a system in place to not only continually assess the knowledge of surgeons throughout their careers, but also to evaluate their practices and techniques during operation. Such an evaluation, however, would put patients at risk during the assessment of the surgeon.

But now a team of researchers from Rensselaer Polytechnic Institute has developed a way of simulating colorectal surgical procedures using virtual reality technology. Suvranu De, Sc.D. — the J. Erik Jonsson ‘22 Distinguished Professor of Engineering and Head of the Department of Mechanical, Aerospace and Nuclear Engineering with joint appointments in Biomedical Engineering and Information Technology and Web Science —leads the project which incorporates both visual and tactile feedback for users to employ as a tool for both training and evaluating colorectal surgeons. While virtual reality simulators have been used for similar applications related to procedures like the colonoscopy, they have yet to be fully developed for open surgical procedures, because of the difficulties in creating a fully engaged and immersive environment. Nonetheless, De and his team hope that their work will lead to the creation of the first “Virtual Intelligent Preceptor,” which will allow for more advanced technological innovations in aspects of surgical education that have so far been difficult to standardize. Support for the project comes from the National Institute of Biomedical Imaging and Bioengineering (NBIB).

Penn BE’s Dr. Bassett on Understanding Knowledge Networks in the Brain

Dr. Danielle Bassett, Ph.D., Eduardo D. Glandt Faculty Fellow and Associate Professor of Bioengineering

As a network neuroscientist, Danielle Bassett, Ph.D., Eduardo D. Glandt Faculty Fellow and Associate Professor in the Department Bioengineering, brings together insights from a variety of fields to understand how the brain’s connections form and change: mathematics, physics, electrical engineering and developmental biology, to name a few. Bassett’s recent work on the learning process also draws from linguistics, educational theory and other domains even further afield.

The intersection and interaction of knowledge from multiple sources doesn’t just describe Bassett’s methodology; it’s at the heart of her research itself. At the Society for Industrial and Applied MathematicsAnnual Meeting last year, Bassett provided an address on how the structure of knowledge networks can influence what our brains can do when it comes to learning new things.

Read the full story on Penn Engineering’s Medium blog.

People & Places:

Tammy Dorsey, a graduate student at Wichita State University, created a non-invasive in utero tool to help read the oxygen levels of unborn babies as part of her senior design project. Dorsey says the inspiration for the project came from complications during the birth of her middle child, who despite having a normal heart rate throughout the entire pregnancy, was born blue. The device Dorsey created uses measurements of the baby’s pH to read fetal oxygen levels. She hopes that the design will help doctors better detect when a fetus is in distress during pregnancy and childbirth.

The field of bioengineering is constantly growing, and new programs are always in development. Boise State University has announced the launch of a new doctoral program in bioengineering that will begin in the fall of 2019. Developed through the collaboration of the university’s College of Health Sciences, College of Engineering, Graduate College, and College of Arts and Sciences, this new opportunity to do research in the field of bioengineering will have three study tracks available in biomechanics, mechanobiology, and human performance.

The new biomedical engineering department at the University of Massachusetts Amherst has announced the department’s first faculty appointments. The founding department head will be Professor Tammy L. Haut Donahue, Ph.D., whose research focus is on the biomechanics of the musculoskeletal system. Another professor joining the department’s new faculty is Seth W. Donahue, Ph.D., who has also done research in the field of biomechanics, and specifically how it pertains to tissue regeneration.

Since we last posted, there have also been several significant academic appointments in the field of Bioengineering. This week, we would like to congratulate Bruce Tromberg, Ph.D., on his appointment as the director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). Dr. Tromberg is currently a Professor with appointments in Biomedical Engineering and Surgery at the University of California at Irvine, where he leads research in bioimaging and biophotonics. He has also served on the External Advisory Board of NIH P41 Center for Magnetic Resonance and Optical Imaging here at Penn since 2009, and has also given several lectures here on his work in bioimaging.

Secondly, we congratulate the University of Toronto’s Professor Warren Chan, Ph.D., who was recently named as a Tier 1 Canada Research Chair in Nanobioengineering. Professor Chan, who is also the director of the Institute of Biomaterials and Biomedical Engineering at the University of Toronto, conducts research in the field of nanotechnology for applications in the treatment and diagnosis of cancer and viral diseases.

And finally, we also want to congratulate Frank Pintar, Ph.D., on his appointment as the Founding Chair of the Marquette University and Medical College of Wisconsin. Dr. Pintar’s research in bioengineering involves the study of the biomechanics involved with brain and spinal cord injury, with a focus on motor vehicle crash trauma.

Penn BE Undergraduates’ Plate Reader Design Published

Microplate reader, Wikimedia Commons

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.

Bioengineering Graduate Group Symposium – January 2019

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

Annual Bioengineering Graduate Group Research Symposium: January 8th

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.

RSVP: https://goo.gl/forms/r4le7koqYnMj3W4m1

Dr. Sujata Bhatia

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 Receives BMES Rising Star Award

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.

BE Seminar Series: November 29th

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.

BE Seminar Series: November 15th

The BE Seminar Series continues this week with two lectures delivered by our current PhD Students. We hope to see you there!

Date: November 15, 2018
Location: Room 337, Towne Building

Claim Extraction for Biomedical Publications

Speaker: Titipat Achikulvisut, Ph.D. Student
Advisor: Konrad Kording, Ph.D.
Time: 12:05-12:25 pm

Abstract:

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

Speaker: Mengjin Dong, Ph.D. Student
Advisor: Paul Yushkevich, Ph.D.
Time: 12:30-12:50 pm

Abstract:

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 Receives NIH Director’s New Innovator Award

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.

Read the full story at Penn Medium.

BE Seminar Series: September 20, 2018

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.

BE Seminar Series starts tomorrow!

Rosalind Picard, ScD, FIEEE

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.