Speaker: Paul Macklin, Ph.D.
Associate Professor, Indiana University
Date: Monday May 4, 2020
Time: 2:00-3:30 PM
Title: “Open Source Multicellular Systems Modeling for Cancer (and COVID-19)”
Paul Macklin is a mathematician, Associate Professor, and Director of Undergraduate studies in the recently-established Department of Intelligent Systems Engineering at Indiana University. He works with biologists, modelers, and clinicians to develop and validate sophisticated 3D computer models of cancer, SARS-CoV-2, and other multicellular systems, using the open source PhysiCell platform developed by his lab. He also works with the National Cancer Institute and the Department of Energy to co-lead a national initiative to create digital twins for the future of personalized predictive cancer medicine.
For the full abstract and registration details, visit the Penn Engineering events calendar.
Some medical conditions, like diabetes or limb amputation, have the potential to result in wounds that never heal, affecting patients for the rest of their lives. Though normal wound-healing processes are relatively understood by medical professionals, the complications that can lead to chronic non-healing wounds are often varied and complex, creating a gap in successful treatments. But biomedical engineering faculty from the University of Connecticut want to change that.
Ali Tamayol, Ph.D., an Associate Professor in UConn’s Biomedical Engineering Department, developed what he’s calling a “smart” bandage in collaboration with researchers from the University of Nebraska-Lincoln and Harvard Medical School. The bandage, paired with a smartphone platform, has the ability to deliver medications to the wound via wirelessly controlled mini needles. The minimally invasive device thus allows doctors to control medication dosages for wounds without the patient even having to come in for an appointment. Early tests of the device on mice showed success in wound-healing processes, and Tamayol hopes that soon, the technology will be able to do the same for humans.
A New Patch Could Fix Broken Hearts
Heart disease is by far one of the most common medical conditions in the world, and has a high risk of morbidity. While some efforts in tissue engineering have sought to resolve cardiac tissue damage, they often require the use of existing heart cells, which can introduce a variety of complications to its integration into the human body. So, a group of bioengineers at Trinity College in Dublin sought to eliminate the need for cells by creating a patch that mimics both the mechanical and electrical properties of cardiac tissue.
Using thermoelastic polymers, the engineers, led by Ussher Assistant Professor in Biomedical Engineering Michael Monaghan, Ph.D., created a patch that could withstand multiple rounds of stretching and exhibited elasticity: two of the biggest challenges in designing synthetic cardiac tissues. With the desired mechanical properties working, the team then coated the patches with an electroconductive polymer that would allow for the necessary electrical signaling of cardiac tissue without decreasing cell compatibility in the patch. So far, the patch has demonstrated success in both mechanical and electrical behaviors in ex vivo models, suggesting promise that it might be able to work in the human body, too.
3-D Printing a New Tissue Engineering Scaffold
While successful tissue engineering innovations often hold tremendous promise for advances in personalized medicine and regeneration, creating the right scaffold for cells to grow on either before or after implantation into the body can be tricky. One common approach is to use 3-D printers to extrude scaffolds into customizable shapes. But the problem is that not all scaffold materials that are best for the body will hold up their structure in the 3-D printing process.
A team of biomedical engineers at Rutgers University led by Chair of Biomedical Engineering David I. Schreiber, Ph.D., hopes to apply the use of hyaluronic acid — a common natural molecule throughout the human body — in conjunction with polyethylene glycol to create a gel-like scaffold. The hope is that the polyethylene glycol will improve the scaffold’s durability, as using hyaluronic acid alone creates a substance that is often too weak for tissue engineering use. Envisioning this gel-like scaffold as a sort of ink cartridge, the engineers hope that they can create a platform that’s customizable for a variety of different cells that require different mechanical properties to survive. Notably, this new approach can specifically control both the stiffness and the ligands of the scaffold, tailoring it to a number of tissue engineering applications.
A New Portable Chip Can Track Wide Ranges of Brain Activity
Understanding the workings of the human brain is no small feat, and neuroscience still has a long way to go. While recent technology in brain probes and imaging allows for better understanding of the organ than ever before, that technology often requires immense amounts of wires and stationary attachments, limiting the scope of brain activity that can be studied. The answer to this problem? Figure out a way to implant a portable probe into the brain to monitor its everyday signaling pathways.
That’s exactly what researchers from the University of Arizona, George Washington University, and Northwestern University set out to do. Together, they created a small, wireless, and battery-free device that can monitor brain activity by using light. The light-sensing works by first tinting some neurons with a dye that can change its brightness according to neuronal activity levels. Instead of using a battery, the device relies on energy from oscillating magnetic fields that it can pick up with a miniature antenna. Led in part by the University of Arizona’s Gutruf Lab, the new device holds promise for better understanding how complex brain conditions like Alzheimer’s and Parkinson’s might work, as well as what the mechanisms of some mental health conditions look like, too.
People & Places
Each year, the National Academy of Engineering (NAE) elects new members in what is considered one of the highest professional honors in engineering. This year, NAE elected 87 new members and 18 international members, including a former Penn faculty member and alumna Susan S. Margulies, Ph.D. Now a professor of Biomedical Engineering at Georgia Tech and Emory University, Margulies was recognized by the NAE for her contributions to “elaborating the traumatic injury thresholds of brain and lung in terms of structure-function mechanisms.” Congratulations, Dr. Margulies!
Nimmi Ramanujam, Ph.D., a Distinguished Professor of Bioengineering at Duke University, was recently announced as having one of the highest-scoring proposals for the MacArthur Foundation’s 100&Change competition for her proposal “Women-Inspired Strategies for Health (WISH): A Revolution Against Cervical Cancer.” Dr. Ramanujam’s proposal, which will enter the next round of competition for the grant, focuses on closing the cervical cancer inequity gap by creating a new model of women-centered healthcare.
A blood test may be able to detect the most common form of pancreatic cancer while it is still in its early stages while also helping doctors accurately stage a patient’s disease and guide them to the appropriate treatment. A multidisciplinary study found the test—known as a liquid biopsy—was more accurate at detecting disease in a blinded study than any other known biomarker alone, and was also more accurate at staging disease than imaging is capable of alone. The team, which includes researchers from the Perelman School of Medicine, the Abramson Cancer Center, and the School of Engineering and Applied Science, published their findings in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the third leading cause of cancer deaths. The overall five-year survival rate is just 9%, and most patients live less than one year following their diagnosis. One of the biggest challenges is catching the disease before it has progressed or spread. If the disease is caught early, patients may be candidates for surgery to remove the cancer, which can be curative. For locally advanced patients—meaning patients whose cancer has not spread beyond the pancreas but who are not candidates for surgery based on the size or location of the tumor—treatment involves three months of systemic therapy like chemo or radiation, then reassessing to see if surgery is an option. For patients whose disease has spread, there are currently no curative treatment options.
“Right now, the majority of patients who are diagnosed already have metastatic disease, so there is a critical need for a test that can not only detect the disease earlier but also accurately tell us who might be at a point where we can direct them to a potentially curative treatment,” says the study’s co-senior author Erica L. Carpenter,director of the Liquid Biopsy Laboratory and a research assistant professor of medicine. The study’s other co-senior author is David Issadore, an associate professor of bioengineering and electrical and systems engineering.
In response to the unprecedented challenges presented by the global outbreak of the novel coronavirus SARS-CoV-2, Penn Bioengineering’s faculty, students, and staff are finding innovative ways of pivoting their research and academic projects to contribute to the fight against COVID-19. Though these projects are all works in progress, I think it is vitally important to keep those in our broader communities informed of the critical contributions our people are making. Whether adapting current research to focus on COVID-19, investing time, technology, and equipment to help health care infrastructure, or creating new outreach and educational programs for students, I am incredibly proud of the way Penn Bioengineering is making a difference. I invite you to read more about our ongoing projects below.
Novel Chest X-Ray Contrast
David Cormode, Associate Professor of Radiology and Bioengineering
The Cormode and Noel labs are working to develop dark-field X-ray imaging, which may prove very helpful for COVID patients. It involves fabricating diffusers that incorporate gold nanoparticles to modify the X-ray beam. This method gives excellent images of lung structure. Chest X-ray is being used on the front lines for COVID patients, and this could potentially be an easy to implement modification of existing X-ray systems. The additional data give insight into the health state of the microstructures (alveoli) in the lung. This new contrast mechanics could be an early insight into the disease status of COVID-19 patients. For more on this research, see Cormode and Noel’s chapter in the forthcoming volume Spectral, Photon Counting Computed Tomography: Technology and Applications, edited by Katsuyuki Taguchi, Ira Blevis, and Krzysztof Iniewski (Routledge 2020).
Computational Models for Targeting Acute Respiratory Distress Syndrome (ARDS). The severe forms of COVID-19 infections resulting in death proceeds by the propagation of the acute respiratory distress syndrome or ARDS. In ARDS, the lungs fill up with fluid preventing oxygenation and effective delivery of therapeutics through the inhalation route. To overcome this major limitation, delivery of antiinflammatory drugs through the vasculature (IV injection) is a better approach; however, the high injected dose required can lead to toxicity. A group of undergraduate and postdoctoral researchers in the Radhakrishnan Lab (Emma Glass, Christina Eng, Samaneh Farokhirad, and Sreeja Kandy) are developing a computational model that can design drug-filled nanoparticles and target them to the inflamed lung regions. The model combines different length-scales, (namely, pharmacodynamic factors at the organ scale, hydrodynamic and transport factors in the tissue scale, and nanoparticle-cell interaction at the subcellular scale), into one integrated framework. This targeted approach can significantly decrease the required dose for combating ARDS. This project is done in collaboration with Clinical Scientist Dr. Jacob Brenner, who is an attending ER Physician in Penn Medicine. This research is adapted from prior findings published in Volume 13, Issue 4 of Nanomedicine: Nanotechnology, Biology and Medicine: “Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions” (May 2017).
Sydney Shaffer, Assistant Professor of Bioengineering and Pathology and Laboratory Medicine
Arjun Raj, David Issadore, and Sydney Shaffer are working on developing an integrated, rapid point-of-care diagnostic for SARS-CoV-2 using single molecule RNA FISH. The platform currently in development uses sequence specific fluorescent probes that bind to the viral RNA when it is present. The fluorescent probes are detected using a iPhone compatible point-of-care reader device that determines whether the specimen is infected or uninfected. As the entire assay takes less than 10 minutes and can be performed with minimal equipment, we envision that this platform could ultimately be used for screening for active COVID19 at doctors’ offices and testing sites. Support for this project will come from a recently-announced IRM Collaborative Research Grant from the Institute of Regenerative Medicine with matching funding provided by the Departments of Bioengineering and Pathology and Laboratory Medicine in the Perelman School of Medicine (PSOM) (PI’s: Sydney Shaffer, Sara Cherry, Ophir Shalem, Arjun Raj). This research is adapted from findings published in the journal Lab on a Chip: “Multiplexed detection of viral infections using rapid in situ RNA analysis on a chip” (Issue 15, 2015). See also United States Provisional Patent Application Serial No. 14/900,494 (2014): “Methods for rapid ribonucleic acid fluorescence in situ hybridization” (Inventors: Raj A., Shaffer S.M., Issadore D.).
HEALTH CARE INFRASTRUCTURE
Penn Health-Tech Coronavirus COVID-19 Collaborations
Brian Litt, Professor of Bioengineering, Neurology, and Neurosurgery
In his role as one of the faculty directors for Penn Health-Tech, Professor Brian Litt is working closely with me to facilitate all the rapid response team initiatives, and in helping to garner support the center and remove obstacles. These projects include ramping up ventilator capacity and fabrication of ventilator parts, the creation of point-of-care ultrasounds and diagnostic testing, evaluating processes of PPE decontamination, and more. Visit the Penn Health-Tech coronavirus website to learn more, get involved with an existing team, or submit a new idea.
Dr. Maltese is rapidly developing a low-cost ventilator that could be deployed in Penn Medicine for the expected surge, and any surge in subsequent waves. This design is currently under consideration by the FDA for Emergency Use Authorization (EUA). This example is one of several designs considered by Penn Medicine in dealing with the patient surge.
David F. Meaney, Solomon R. Pollack Professor of Bioengineering and Senior Associate Dean
Led by David Meaney, Kevin Turner, Peter Bruno and Mark Yim, the face shield team at Penn Health-Tech is working on developing thousands of rapidly producible shields to protect and prolong the usage of Personal Protective Equipment (PPE). Learn more about Penn Health-Tech’s initiatives and apply to get involved here.
Update 4/29/20: The Penn Engineering community has sprung into action over the course of the past few weeks in response to COVID-19. Dr. Meaney shared his perspective on those efforts and the ones that will come online as the pandemic continues to unfold. Read the full post on the Penn Engineering blog.
OUTREACH & EDUCATION
Student Community Building
Yale Cohen, Professor of Otorhinolaryngology, Department of Psychology, BE Graduate Group Member, and BE Graduate Chair
Yale Cohen, and Penn Bioengineering’s Graduate Chair, is working with Penn faculty and peer institutions across the country to identify intellectually engaging and/or community-building activities for Bioengineering students. While those ideas are in progress, he has also worked with BE Department Chair Ravi Radhakrishnan and Undergraduate Chair Andrew Tsourkas to set up a dedicated Penn Bioengineering slack channel open to all Penn Bioengineering Undergrads, Master’s and Doctoral Students, and Postdocs as well as faculty and staff. It has already become an enjoyable place for the Penn BE community to connect and share ideas, articles, and funny memes.
Undergraduate Course: Biotechnology, Immunology, Vaccines and COVID-19 (ENGR 35)
Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor of Bioengineering and Chemical and Biomolecular Engineering
This Summer Session II, Professor Dan Hammer and CBE Senior Lecturer Miriam R. Wattenbarger will teach a brand-new course introducing Penn undergraduates to a basic understanding of biological systems, immunology, viruses, and vaccines. This course will start with the fundamentals of biotechnology, and no prior knowledge of biotechnology is necessary. Some chemistry is needed to understand how biological systems work. The course will cover basic concepts in biotechnology, including DNA, RNA, the Central Dogma, proteins, recombinant DNA technology, polymerase chain reaction, DNA sequencing, the functioning of the immune system, acquired vs. innate immunity, viruses (including HIV, influenza, adenovirus, and coronavirus), gene therapy, CRISPR-Cas9 editing, drug discovery, types of pharmaceuticals (including small molecule inhibitors and monoclonal antibodies), vaccines, clinical trials. Some quantitative principles will be used to quantifying the strength of binding, calculate the dynamics of enzymes, writing and solving simple epidemiological models, methods for making and purifying drugs and vaccines. The course will end with specific case study of coronavirus pandemic, types of drugs proposed and their mechanism of action, and vaccine development.
Update 4/29/20: Read the Penn Engineering blog post on this course published April 27, 2020.
Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science
Dr. Kording facilitated Neuromatch 2020, a large virtual neurosciences conferences consisting of over 3,000 registrants. All of the conference talk videos are archived on the conference website and Dr. Kording has blogged about what he learned in the course of running a large conference entirely online. Based on the success of Neuromatch 1.0, the team are now working on planning Neuromatch 2.0, which will take place in May 2020. Dr. Kording is also working on facilitating the transition of neuroscience communication into the online space, including a weekly social (#neurodrinking) with both US and EU versions.
Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science
Dr. Kording is working to launch the Neuromatch Academy, an open, online, 3-week intensive tutorial-based computational neuroscience training event (July 13-31, 2020). Participants from undergraduate to professors as well as industry are welcome. The Neuromatch Academy will introduce traditional and emerging computational neuroscience tools, their complementarity, and what they can tell us about the brain. A main focus is not just on using the techniques, but on understanding how they relate to biological questions. The school will be Python-based making use of Google Colab. The Academy will also include professional development / meta-science, model interpretation, and networking sessions. The goal is to give participants the computational background needed to do research in neuroscience. Interested participants can learn more and apply here.
Journal of Biomedical Engineering Call for Review Articles
Beth Winkelstein, Vice Provost for Education and Eduardo D. Glandt President’s Distinguished Professor of Bioengineering
The American Society of Medical Engineers’ (ASME) Journal of Biomechanical Engineering (JBME), of which Dr. Winkelstein is an Editor, has put out a call for review articles by trainees for a special issue of the journal. The call was made in March 2020 when many labs were ramping down, and trainees began refocusing on review articles and remote work. This call continues the JBME’s long history of supporting junior faculty and trainees and promoting their intellectual contributions during challenging times.
Update 4/29/20: CFP for the special 2021 issue here.
Are you a Penn Bioengineering community member involved in a coronavirus-related project? Let us know! Please reach out to firstname.lastname@example.org.
The Office of the Provost awards the Penn Prize for Excellence in Teaching by Graduate Students in recognition of their profound impact on education across the University. Nominations come directly from undergraduate and graduate students in their courses and are narrowed down to ten awardees each year.
Muir has served as a teaching assistant for coursework in Biomaterials with Skirkanich Assistant Professor of Innovation Michael Mitchell and Tissue Engineering with Robert D. Bent Professor Jason Burdick. She is conducting her thesis on granular hydrogels for musculoskeletal tissue repair under Burdick’s advisement. Muir has also received both NSF and Tau Beta Pi Fellowships for her graduate studies.
The Department of Bioengineering is proud to congratulate Whelton Miller, Ph.D., a former BE Postdoctoral Fellow, on his appointment as an Assistant Professor in the Department of Medicine in the Health Sciences Division at Loyola University. Miller’s appointment began in January 2020.
Miller received his B.S. in Biochemistry in 2001 from the University of Delaware where he worked under the supervision of Dr. Douglass F. Taber. After graduation, he worked in industry as a synthetic organic chemist for a pharmaceutical company. After three years of industry experience, he returned to academia to complete a Ph.D. in Theoretical/Computational Chemistry from the University of the Sciences in Philadelphia in 2012.
Miller joined Loyola University in Chicago, IL in the summer of 2019. Now in his new faculty position, Miller continues to work on collaborative research projects and include colleagues at Instituto Tecnológico de Santo Domingo, the University of Pennsylvania, Lincoln University, University of Ghana, and the University of the Sciences. His current research involves using computational chemistry techniques for theoretical design and study of organometallic and inorganic compounds, protein ligand interactions, and structural electronic effects. His goal is to employ several computational techniques to understand, as well as predict, molecular interactions, such as protein-ligand interactions and protein-protein interactions. Miller says he is always looking forward to more opportunities for minority student development and enrichment in the STEM-related disciplines. Congratulations, Dr. Miller!
Almost every engineering school in the country offers a course in mechatronics — the overlap of mechanical, electrical, and computer engineering in electromechanical system design — but how many offer a course in biomechatronics? Taught by LeAnn Dourte, Ph.D., a Practice Associate Professor in Bioengineering, Penn Engineering’s Biomechatronics course (BE 570) gives students the chance to think about how the principles of mechatronic design can be used in biological settings involving orthopaedics, cardiovascular systems, and respiration, to name a few.
Throughout the course, students engage in different projects related to circuitry, signal processing, mechanics, motors, and analog controls, eventually applying all of these to biological examples before working on a final culminating project in design teams of two. In a simulation meant to mimic the sort of thinking and design processes that go behind innovations in robotic surgery, students create an electromechanical device that acts as a robotic hand. The catch? The “hand” has to have enough dexterity to pick up a water bead with a slipperiness similar to that of human tissue.
In addition to successfully performing this mechanical task using skills that the students learned throughout the semester, design teams also have to incorporate biological interfaces into the final project, such as using EMG signals to move part of the robotic hand, to give one example. Furthermore, each team needs to have a unique element to their design, whether in the use of a second biological interface, the application of Bluetooth to the system, or even a physical extension of the robotic hand to include the electromechanical equivalents of a shoulder, elbow, or wrist joint.
Students Carolyn Godone and Mike Furr (both M.S.E. in Bioengineering ‘19) created a design inspired by the mechanical iris of a camera lens, using gears to push 3-D printed slices together in a symmetrical pattern to close around an object for pickup. They controlled their unique gripper with a thermal sensing camera that could employ a heat map of the device’s user to rotate, raise, and lower the gripper. Another pair of students, Omar Abdoun (BE M.D./Ph.D. student) and Andrew Chan (M.S.E. in Robotics ‘19), made what they called a “cryogripper”: a tissue moistened with water that freezes on demand when it contacts its target hydrogel. The ice allows the target to be lifted without falling, and the tissue can later be thawed with pumps of warm water to release hydrogel.
Spencer Glantz, a graduate of the Penn Bioengineering doctoral program and former member of the Brian Chow Lab, was mentioned in a recent WHYY piece highlighting the efforts of Penn labs to develop rapid, at-home testing for COVID-19. Glantz is currently a co-leader of the molecular biology team for 4Catalyzer, a medical device incubator founded by National Medal of Technology and Innovation recipient, and sponsor of the annual Rothberg Catalyzer Makerthon competition, Jonathan Rothberg. 4Catalyzer is developing the testing technology while Penn researchers are working to evaluate its effectiveness.
Originally from Matawan, NJ, Riley has been an NIH Postdoctoral Fellow in the Mitchell Lab since 2018. Her move to a faculty position at Rowan marks a return, as she received her B.S. in Civil and Environmental Engineering there in 2012. Riley went on to receive her Ph.D. in Biomedical Engineering in 2018 at the University of Delaware with Emily Day, Ph.D. before joining the lab of Michael J. Mitchell, Ph.D., Skirkanich Assistant Professor of Innovation, later that year. The Mitchell Lab’s research lies at the interface of biomaterials science, drug delivery, and cellular and molecular bioengineering to fundamentally understand and therapeutically target biological barriers.
“Rachel has had a prolific academic career at the University of Delaware and at Penn, launching several exciting research projects and mentoring the next generation of STEM researchers,” Mitchell says. “I’m very hopeful that her new position as an Assistant Professor of Biomedical Engineering at Rowan University will permit her to engineer new drug delivery technologies for women’s health applications.”
Research in the Riley Lab at Rowan will explore how nanoparticle drug delivery technologies can be engineered specifically for applications in women’s health. They will use nanoparticles as tools to study and treat gynecological cancers, fetal diseases, and pregnancy complications. Riley’s ultimate goal is to gain a fundamental understanding of how nanoparticle structure influences delivery to gynecological tissues to enable them to take an engineering approach to tackle new applications in women’s health.
Riley says that she is committed to supporting women and minorities in STEM disciplines and she looks forward to continuing collaborations with Penn and starting new collaborations with researchers at Cooper Medical School at Rowan University (CMSRU). Congratulations, Dr. Riley!
Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer. College membership honors those who have made outstanding contributions to “engineering and medicine research, practice, or education” and to “the pioneering of new and developing fields of technology, making major advancements in traditional fields of medical and biological engineering, or developing/implementing innovative approaches to bioengineering education.”
Bassett was nominated, reviewed, and elected by peers and members of the College of Fellows for “significant contributions to the application of neural network theory for understanding both physio and patho-physiological brain function.”
As a result of health concerns, AIMBE’s annual meeting and induction ceremony scheduled for March 29–30, 2020, was cancelled. Under special procedures, Bassett was remotely inducted along with 156 colleagues who make up the AIMBE College of Fellows Class of 2020.