Week in BioE (July 12, 2019)

by Sophie Burkholder

DNA Microscopy Gives a Better Look at Cell and Tissue Organization

A new technique that researchers from the Broad Institute of MIT and Harvard University are calling DNA microscopy could help map cells for better understanding of genetic and molecular complexities. Joshua Weinstein, Ph.D., a postdoctoral associate at the Broad Institute, who is also an alumnus of Penn’s Physics and Biophysics department and former student in Penn Bioengineering Professor Ravi Radhakrishnan’s lab, is the first author of this paper on optics-free imaging published in Cell.

The primary goal of the study was to find a way of improving analysis of the spatial organization of cells and tissues in terms of their molecules like DNA and RNA. The DNA microscopy method that Weinstein and his team designed involves first tagging DNA, and allowing the DNA to replicate with those tags, which eventually creates a cloud of sorts that diffuses throughout the cell. The DNA tags subsequent interactions with molecules throughout the cell allowed Weinstein and his team to calculate the locations of those molecules within the cell using basic lab equipment. While the researchers on this project focused their application of DNA microscopy on tracking human cancer cells through RNA tags, this new method opens the door to future study of any condition in which the organization of cells is important.

Read more on Weinstein’s research in a recent New York Times profile piece.

Penn Engineers Demonstrate Superstrong, Reversible Adhesive that Works like Snail Slime

A snail’s epiphragm. (Photo: Beocheck)

If you’ve ever pressed a picture-hanging strip onto the wall only to realize it’s slightly off-center, you know the disappointment behind adhesion as we typically experience it: it may be strong, but it’s mostly irreversible. While you can un-stick the used strip from the wall, you can’t turn its stickiness back on to adjust its placement; you have to start over with a new strip or tolerate your mistake. Beyond its relevance to interior decorating, durable, reversible adhesion could allow for reusable envelopes, gravity-defying boots, and more heavy-duty industrial applications like car assembly.

Such adhesion has eluded scientists for years but is naturally found in snail slime. A snail’s epiphragm — a slimy layer of moisture that can harden to protect its body from dryness — allows the snail to cement itself in place for long periods of time, making it the ultimate model in adhesion that can be switched on and off as needed. In a new study, Penn Engineers demonstrate a strong, reversible adhesive that uses the same mechanisms that snails do.

This study is a collaboration between Penn Engineering, Lehigh University’s Department of Bioengineering, and the Korea Institute of Science and Technology.

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

Low-Dose Radiation CT Scans Could Be Improved by Machine Learning

Machine learning is a type of artificial intelligence growing more and more popular for applications in bioengineering and therapeutics. Based on learning from patterns in a way similar to the way we do as humans, machine learning is the study of statistical models that can perform specific tasks without explicit instructions. Now, researchers at Rensselaer Polytechnic Institute (RPI) want to use these kinds of models in computerized tomography (CT) scanning by lowering radiation dosage and improving imaging techniques.

A recent paper published in Nature Machine Intelligence details the use of modularized neural networks in low-dose CT scans by RPI bioengineering faculty member Ge Wang, Ph.D., and his lab. Since decreasing the amount of radiation used in a scan will also decrease the quality of the final image, Wang and his team focused on a more optimized approach of image reconstruction with machine learning, so that as little data as possible would be altered or lost in the reconstruction. When tested on CT scans from Massachusetts General Hospital and compared to current image reconstruction methods for the scans, Wang and his team’s method performed just as well if not better than scans performed without the use of machine learning, giving promise to future improvements in low-dose CT scans.

A Mind-Controlled Robotic Arm That Requires No Implants

A new mind-controlled robotic arm designed by researchers at Carnegie Mellon University is the first successful noninvasive brain-computer interface (BCI) of its kind. While BCIs have been around for a while now, this new design from the lab of Bin He, Ph.D.,  a Trustee Professor and the Department Head of Biomedical Engineering at CMU, hopes to eliminate the brain implant that most interfaces currently use. The key to doing this isn’t in trying to replace the implants with noninvasive sensors, but in improving noisy EEG signals through machine learning, neural decoding, and neural imaging. Paired with increased user engagement and training for the new device, He and his team demonstrated that their design enhanced continuous tracking of a target on a computer screen by 500% when compared to typical noninvasive BCIs. He and his team hope that their innovation will help make BCIs more accessible to the patients that need them by reducing the cost and risk of a surgical implant while also improving interface performance.

People and Places

Daeyeon Lee, professor in the Department of Chemical and Biomolecular Engineering and member of the Bioengineering Graduate Group Faculty here at Penn, has been selected by the U.S. Chapter of the Korean Institute of Chemical Engineers (KIChE) as the recipient of the 2019 James M. Lee Memorial Award.

KIChE is an organization that aims “to promote constructive and mutually beneficial interactions among Korean Chemical Engineers in the U.S. and facilitate international collaboration between engineers in U.S. and Korea.”

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

We would also like to congratulate Natalia Trayanova, Ph.D., of the Department of Biomedical Engineering at Johns Hopkins University on being inducted into the Women in Tech International (WITI) Hall of Fame. Beginning in 1996, the Hall of Fame recognizes significant contributions to science and technology from women. Trayanova’s research specializes in computational cardiology with a focus on virtual heart models for the study of individualized heart irregularities in patients. Her research helps to improve treatment plans for patients with cardiac problems by creating virtual simulations that help reduce uncertainty in either diagnosis or courses of therapy.

Finally, we would like to congratulate Andre Churchwell, M.D., on being named Vanderbilt University’s Chief Diversity Officer and Interim Vice Chancellor for Equity, Diversity, and Inclusion. Churchwell is also a professor of medicine, biomedical engineering, and radiology and radiological sciences at Vanderbilt, with a long career focused in cardiology.

Week in BioE (June 14, 2019)

by Sophie Burkholder

Bio-inspiration Informs New Football Helmet Design from IUPUI Students

Art, design, biology, and engineering all interact with each other in a recent design for a football helmet from two students one of media arts and the other of engineering at the Indiana University – Purdue University Indianapolis. Directed by Lecturer in Media Arts and Science Zebulun Wood, M.S., and Associate Professor of Mechanical and Energy Engineering and Assistant Professor of Biomedical Engineering Andres Tovar, Ph.D., the students found inspiration in biological structures like a pomelo peel, nautilus shell, and woodpecker skull to create energy-absorbing helmet liners. The resulting design took these natural concussion-reducing structures and created compliant mechanism lattice-based liners the replace the foam traditionally placed in between two harder shells of a typical helmet. Their work not only exemplifies the benefits of bio-inspiration, but demonstrates the way that several different domains of study can overlap in the innovation of a new product.

Study of Mechanical Properties of Hyaluronic Acid Could Help Inform Current Debates Over Treatment Regulation for Osteoarthritis

Arthritis is an extremely common condition, especially in older patients, in which inflammation of the joints can cause high amounts of stiffness and pain. Osteoarthritis in particular is the result of the degradation of flexible tissue between the bones of a joint, which increases friction in joint motion. A common treatment of this form of arthritis is the injection of hyaluronic acid, which is meant to provide joint lubrication, and decreases this friction between bones. Recently, however, there has been a debate over hyaluronic acid’s classification by the FDA and whether it should remain based on the knowledge of the mechanical actions of the acid in treatment for osteoarthritis or if potential chemical action of the acid should be considered as well.

Because of limited ways of testing the mechanical properties of the acid, many researchers felt that there could be more to hyaluronic acid’s role in pain relief for arthritic patients. But Lawrence Bonassar, Ph.D., the Daljit S. and Elaine Sarkaria Professor in Biomedical Engineering at the Meinig School of Bioengineering of Cornell University, had another idea. With his lab, he created a custom-made tribometer to measure the coefficient of friction of a given lubricant by rubbing a piece of cartilage back and forth across a smooth glass plate. The research demonstrated that hyaluronic acid’s ability to reduce the coefficient of friction aligned with patients’ pain relief. Bonassar and his team hope that these results will demonstrate the heavy contribution of mechanical action that hyaluronic acid has in osteoarthritis treatment, and help bring an end to the debate over its FDA classification.

A New Way of Mapping the Heart Could Lead to Better Understanding of Contractile Activity

Though reduced contractions in certain regions of the heart can be an indicator of a certain condition, there is currently no way to directly measure contractile activity. This is why Cristian Linte, Ph.D., an Associate Professor of Biomedical Engineering in the Kate Gleason College of Engineering at the Rochester Institute of Technology (RIT), hopes to create a map of the heart that can quantify contraction power. In collaboration with Niels Otani, Ph.D., an Associate Professor in the School of Mathematics at RIT, Linte plans to use an $850,000 grant from the National Science Foundation to achieve a more comprehensive understanding of the heart through both medical imaging and mechanical modeling. The group hopes that their approach will lead to not only a better way to diagnose certain heart conditions and diseases, but also open up understanding of active contraction, passive motion, and the stresses within the heart walls that underlie each.

Celebrity Cat Lil Bub Helps Penn and German Researchers Draw Public Attention to Genetics

Lil Bub’s unique appearance has garnered millions of online fans, and now, an avenue for researchers to talk about genetics. (Photo Courtesy of Mike Bridavsky)

In 2015, a group of curious researchers set out to sequence the genome of a celebrity cat named Lil Bub. They were hoping to understand the genetics behind Lil Bub’s extra toes and unique skeletal structure, which contribute to her heart-warming, kitten-like appearance. However, an equally important goal of their “LilBUBome” project was to invite the general public into the world of genetics.

Orsolya “Uschi” Symmons, a postdoctoral researcher at Penn in Associate Professor of Bioengineering Arjun Raj’s lab, led the research team along with Darío Lupiáñez at the Max-Delbrück Center for Molecular Medicine in Berlin, and Daniel Ibrahim at the Max Planck Institute for Molecular Geneticsin Berlin. Lil Bub’s owner, Mike Bridavsky, also contributed to the project.

Because of Lil Bub’s online fame, the project garnered attention from her fans and the media, all hoping to discover the secret to Lil Bub’s charm. As early as 2015, Gizmodo’s Kiona Smith-Strickland reported on the team’s intentions to sequence Lil Bub’s genome, and, since then, many have been awaiting the results of the LilBUBome.

To read more of this story, visit Penn Engineering’s Medium Blog.

People and Places

The Alfred P. Sloan Foundation awarded a six-year grant to Barnard College and Columbia University’s School of Engineering and Applied Science to support graduate education for women in engineering. The funding will go towards a new five-year program that enables Barnard students to attain both a B.A. and M.S. in one year after their traditional four years of undergraduate education. The program will offer M.S. degrees in chemical engineering, biomedical engineering, and industrial engineering and operations research, and is one of the first of its kind for women’s colleges.

We would like to congratulate Jean Paul Allain, Ph.D., on being named the first head of the new Ken and Mary Alice Lindquist Department of Nuclear Engineering at Penn State. Allain, who is currently a Professor and head of graduate programs in the University of Illinois at Urbana-Champaign’s Department of Nuclear, Plasma, and Radiological Engineering, conducts research in models of particle-surface interactions. In addition to being head of the new department at Penn State, Allain will also hold a position as a Professor of Biomedical Engineering at the university.

We would also like to congratulate Andrew Douglas, Ph.D., on his appointment as the Vice Provost for Faculty Affairs at Johns Hopkins University. Douglas currently holds the position of Vice Dean for Faculty at the Whiting School of Engineering, and has joint appointments in Mechanical and Biomedical Engineering. Douglas’s research at Hopkins focuses on mechanical properties and responses of compliant biological tissue and on the nonlinear mechanics of solids, with a focus on soft tissues and organs like the heart and tongue.

Week in BioE: April 5, 2019

by Sophie Burkholder

Tulane Researchers Use Cancer Imaging Technique to Help Detect Preeclampsia

Preeclampsia is potentially life-threatening pregnancy disorder that typically occurs in about 200,000 expectant mothers every year. With symptoms of high blood pressure, swelling of the hands and feet, and protein presence in urine, preeclampsia is usually treatable if diagnosed early enough. However, current methods for diagnosis involve invasive procedures like cordocentesis, a procedure which takes a sample of fetal blood.

Researchers at Tulane School of Medicine led by assistant professor of bioengineering Carolyn Bayer, Ph.D., hope to improve diagnostics for preeclampsia with the use of spectral photoacoustic imaging. Using this technique, Bayer’s team noticed a nearly 12 percent decrease in placental oxygenation in rats with induced preeclampsia when compared to normal pregnant rats after only two days. If success in using this imaging technology continues at the clinical level, Bayer plans to find more applications of it in the detection and diagnosis of breast and ovarian cancers as well.

New CRISPR-powered device detects genetic mutations in minutes 

Two groups of researchers from the University of California, Berkeley and the Keck Graduate Institute of the Claremont Colleges recently collaborated to design what they call a “CRISPR-Chip” –  a combination of the CRISPR-Cas9 System with a graphene transistor to sequence DNA for the purpose of genetic mutation diagnosis. While companies like 23andMe made genetic testing and analysis more common and accessible for the general public in recent years, the CRISPR-Chip looks to streamline the technology even more.

This new chip eliminates the long and expensive amplification process involved in the typical polymerase chain reaction (PCR) used to read DNA sequences. In doing so, the CRISPR-Chip is much more of a point-of-care diagnostic, having the ability to quickly detect a given mutation or sequence when given a pure DNA sample. Led by Kiana Aran, Ph.D., the research team behind the CRISPR-Chip hopes that this new combination of nanoelectronics and modern biology will allow for a new world of possibilities in personalized medicine.

New Method of Brain Stimulation Might Alleviate Symptoms of Depression

Depression is one of the most common mental health disorders in the United States, with nearly 3 million cases every year. For most patients suffering from depression, treatment involves prolonged psychotherapy, antidepressant medication, or even electroconvulsive therapy in extreme cases. Now, scientists at the University of North Carolina School of Medicine study the use of transcranial alternating current stimulation (tACS) to alleviate symptoms of depression.

Led by Flavio Frohlich, Ph.D., who has an adjunct appointment in biomedical engineering, this team of researchers based this new solution on information from each patient’s specific alpha oscillations, which are a kind of wave that can be detected by an electroencephalogram (EEG). Those who suffer from depression tend to have imbalanced alpha oscillations, so Frohlich and his team sought to use tACS to restore this balance in those patients. After seeing positive results from data collected two weeks after patients in a clinical trial receives the tACS treatment, Frohlich hopes that future applications will include treatment for even more mental health disorders and psychiatric illnesses.

University of Utah Researchers Receive Grant to Improve Hearing Devices for Deaf Patients

Engineers at the University of Utah are part of team that recently received a $9.7 million grant from the National Institute of Health (NIH) to design new implantable hearing devices for deaf patients, with the hope to improve beyond the sound quality of existing devices. The work will build upon a previous project at the University of Utah called the Utah Electrode Array, a brain-computer interface originally developed by Richard Normann, Ph.D., that can send and receive neural impulses to and from the brain. This new device will differ from a typical cochlear implant because the Utah Electrode Array assembly will be attached directly to the auditory nerve instead of the cochlea, providing the patient with a much higher resolution of sound.

People & Places

Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Scholar in the Department of Materials Science and Engineering and Secondary Faculty in Bioengineering, has been named the recipient of the 2018–19 George H. Heilmeier Faculty Award for Excellence in Research for “for pioneering multi-scale models of nanomaterials and biological systems.”

The Heilmeier Award honors a Penn Engineering faculty member whose work is scientifically meritorious and has high technological impact and visibility. It is named for George H. Heilmeier, a Penn Engineering alumnus and overseer whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize.

Read the rest of the story on Penn Engineering’s Medium blog.

We would also like to congratulate Jay Goldberg, Ph.D., from Marquette University on his election as a fellow to the National Academy of Inventors. Nominated largely for his six patents involving medical devices, Goldberg also brings this innovation to his courses. One in particular called Clinical Issues in Biomedical Engineering Design allows junior and senior undergraduates to observe the use of technology in clinical settings like the operating room, in an effort to get students thinking about how to improve the use of medical devices in these areas.

 

Bioengineering Welcomes New Faculty Member Sydney Shaffer

Sydney Shaffer, MD, PhD

The Department of Bioengineering at the University of Pennsylvania is proud to announce the appointment of Sydney Shaffer, Ph.D., as an Assistant Professor of Bioengineering. She shares a joint appointment with Pathology and Laboratory Medicine. Originally from Atlanta, GA, Dr. Shaffer received her B.S. in Chemical Engineering from Georgia Institute of Technology, coming to Penn to complete her M.D./Ph.D. work in Bioengineering and the Perelman School of Medicine. After graduating in 2018, she conducted her postdoctoral work at Penn in Cancer Biology with Dr. Junwei Shi.

Dr. Shaffer’s research is is focused on understanding how differences present in single-cells can generate phenotypes such as drug resistance in cancer, oncogenesis, differentiation, and invasion. Our approach leverages cutting-edge technologies including high-throughput imaging, single-molecule RNA FISH, fluorescent protein tagging, CRISPR/Cas9 screening, and flow cytometry to investigate rare single-cell phenomena. Further information can be found at www.sydshafferlab.com.

In addition to her exciting research, Dr. Shaffer will be an enthusiastic new member of the Bioengineering Department community. In the short term, she will be taking over the popular class BE 400 (Preceptorships in Bioengineering) which gives undergraduates the rare chance to shadow renowned physicians over a period of ten weeks. She will also serve as a faculty advisor as well as a mentor to the lucky students in her classes and lab.

Dr. Shaffer says that, “With my research interests and training at the interface of engineering and medicine, I am thrilled to be part of the highly interdisciplinary community of Penn Bioengineering.”

“Sydney has a unique combination of creativity and impact in her work,” says Solomon R. Pollack Professor and Chair Dr. David Meaney. “Her work to untangle the secrets of how single cancer cells can develop resistance to a cancer drug  therefore leading to a return of the cancer  is nothing short of stunning. We are incredibly fortunate to have her on our faculty. ”

Week in BioE (June 19, 2018)

Dolphin Echolocation Could Improve Ultrasound

dolphin echolocationDolphins are among the most intelligent creatures on earth, showing behaviors such as teaching, learning, cooperation, delayed gratification, and other markers of high intelligence. Dolphins communicate vocally with one another, although we aren’t sure exactly what they communicate. While this communication isn’t “language” as humans define it, it uses echolocation — finding objects and orienteering on the basis of reflected sound — which humans don’t use in their communications.

Now, we have new information about dolphin echolocation thanks to an article recently published in the Journal of the Acoustical Society of America by mathematicians and biomedical engineers in Sweden.  On the basis of earlier research finding that dolphin echolocation signals consist of two tones, rather than one, the new study finds that these two tones are emitted at slightly different times and that the sound waves have a Gaussian shape, similar to a bell curve. Using a mathematical algorithm, the authors successfully simulated echolocation signals in the lab.

The findings explain how dolphins use echolocation effectively but could also contribute to more accurate sound-based diagnostic techniques — particularly ultrasound, which relies heavily on methods similar to echolocation to provide images of moving tissues within the body, e.g., prenatal imaging and heart contraction.

Modeling Diseased Blood Vessels for Drug and Device Testing

Drugs and devices require extensive testing before they are approved by regulatory agencies and used to treat human patients. Tissue engineering has helped bridge the gap between a promising idea and its use in a patient by creating technologies that mimic the complex structure of human tissue. Most of these technologies focus on the engineering of healthy tissues and much less on constructing models of diseased tissue. These models of diseased tissue may be useful for designing treatments for diseases and understanding how diseases are caused.

In this light, Marsha W. Rolle, PhD, Associate Professor of Biomedical Engineering at Worcester Polytechnic Institute (WPI), is working to create engineered blood vessels that are already diseased as a way to test possible treatments. With three years of funding from the National Institutes of Health’s National Heart Lung and Blood Institute amounting to nearly $500,000, Dr. Rolle and her research team create these damaged vessels by engineering smooth muscle cells to form tubes 2 mm in diameter. These synthetic vessels are then modified to resemble features of diseases. For example, growth factors attached to microspheres can encourage the growth of tissue in small parts of the vessel wall, eventually becoming areas of narrowing in the vessel. Similarly, other factors could lead to changes in the vessel that resemble aneurysms. In both cases, the function of the microengineered vessel could be measured as the change happens, providing insight into either vascular stenosis or aneurysms, neither of which is possible in humans.

Dr. Rolle’s first step will be to test the damaged engineered vessels with existing medications. If successful, this new technique could be used for testing of new drugs and devices prior to testing in animals.

New Heart Implant Can Deliver Drug

Speaking of damage to the circulatory system, a new article in Nature Biomedical Engineering details how engineers at MIT, Harvard, and Trinity College, Dublin, created a heart implant that can deliver targeted therapy to damaged heart tissue. The authors, led in part by Conor J. Walsh, PhD, and David J. Mooney, PhD, of Harvard, created a device called Therepi, approximately 4 mm in size, which is deployed with a hypodermic. Once placed, a reservoir of medicine within the Therepi treats the damaged heart muscle. In addition, it can be refilled without needing to remove the implant. The Nature Biomedical Engineering study is limited to testing in rats, but the authors see testing in humans in the near future.

Erdős-Rényi Prize for Penn Professor

Danielle S. Bassett, PhD, Eduardo D. Glandt Faculty Fellow and Associate Professor of Bioengineering at the University of Pennsylvania, has been named the 2018 recipient of the Erdős-Rényi Prize in Network Science by the Network Science Society (NetSci). NetSci has recognized Dr. Bassett for “fundamental contributions to our understanding of the network architecture of the human brain, its evolution over learning and development, and its alteration in neurological disease.” Dr. Bassett will receive the award and deliver a lecture on June 14 at the International Conference on Network Science in Paris. She is the seventh scientist and fourth American to receive the prize.

The Erdős-Rényi Prize is awarded annually to a scientist younger than 40 years old for his/her achievements in the field of network science. It is named for the Hungarian mathematicians Paul Erdős, whose surname provided a measurement for research collaboration by academic mathematicians, and Alfréd Rényi, whose work focused on probability and graph theory. In network science, an Erdős-Rényi model is a model for generating random graphs. Dr. Bassett’s research applies the principles of network science in neuroscience, with the intention of understanding the brain better by modeling the networks and circuits of our most complex organ.

People and Places

Two new centers dedicated to health sciences are opening. Western New England University opened its new Center for Global Health Engineering in April, with Michael J. Rust, PhD, Associate Professor of Biomedical Engineering, as the codirector under director Christian Salmon, PhD. Elsewhere, Northwestern University launched a new center — the Center for Advanced Regenerative Engineering — with Guillermo Ameer, PhD, Daniel Hale Williams Professor of Biomedical Engineering and Surgery at Northwestern, as founding director.

Finally, Joseph J. Pancrazio, Ph.D., Professor of Bioengineering at the University of Texas at Dallas and Associate Provost,  has been named Vice President for Research. Before moving to UT Dallas in 2015, Dr. Pancrazio was the founding chair of Bioengineering at George Mason University in Virginia.

Week in BioE (April 24, 2018)

Pushing the Limits of Imaging

7T-MRI
An image showing 7-tesla MRI of the human brain

Since the late 1970s with the advent of computed tomography (CT), medical imaging has grown exponentially. Magnetic resonance imaging (MRI) offers some of the clearest pictures of human anatomy and pathology, particularly as the strength of the magnetic field used (measured in units called Teslas) increases. However, MRI machines are expensive, and the costs increase as one uses a machine with higher field strength to ‘see’ the human more closely. Therefore, it is often more useful (and certainly less expensive) to modify existing MRI technology on hand, rather than acquire a new machine.

A recent example is the work of Tamer Ibrahim, PhD, Associate Professor of Bioengineering at the University of Pittsburgh. Dr. Ibrahim used a series of multiple NIH grants to develop a coil system for Pitt’s 7T-MRI — one of only approximately 60 worldwide — enabling it to more accurately image the brain’s white matter. Dr. Ibrahim is interested in seeing how hyperintensity in the white matter is related to depression, which is one of the highest-burden but least-discussed diseases in the world. Called a “tic-tac-toe” radiofrequency coil setting, the device that Dr. Ibrahim created is a network of antennas fitted to the head that minimize concerns such as coil heating and radiofrequency intensity losses, as well as safety concerns.

Dr. Ibrahim has more NIH funding on the way to continue optimizing his device and apply it in other psychiatric and neurological disorders. Rather than purchasing a new MRI machine with higher field strengths to achieve this image quality, Dr. Ibrahim’s coil design can be used on existing machines. One possible outcome is more clinicians using this new coil to study how changes in the brain’s white matter structure occur in a broad range of brain diseases, leading to both earlier detection anfor ad more effective treatment.

Smart Shunt for Hydrocephalus

Hydrocephalus, once more commonly known as “water on the brain,” is a condition marked by abnormal accumulation of cerebrospinal fluid (CSF) in the skull. If unchecked, the accumulation of fluid will create dangerous pressures in the brain that can result in brain damage. Hydrocephalus occurs in one in every 1,000 births, and nearly 400,000 adults in the US suffered at least on episode of hydrocephalus. For both infants and adults, hydrocephalus is often treated surgically with the installation of a shunt to channel the excess CSF out of the cranium. These shunts are simple but effective devices that operate mechanically. However, since they’re entirely mechanical, they fail over time. Being able to determine that such a failure was imminent could allow patients to receive a replacement shunt before complications arise.

To meet this clinical need, a group of scientists at the University of Southern California (USC)  updated existing shunt systems with microsensing technology, creating a “smart shunt” that can tell clinicians how an installed shunt is functioning and alert the clinician that a replacement is needed. The group, including Ellis Fan-Chuin Meng, PhD, Gabilan Distinguished Professorship in Science and Engineering, Dwight C. and Hildagarde E. Baum Chair, and Professor of Biomedical Engineering and Electrical Engineering-Electrophysics, has created a start-up called Senseer to produce these smart shunts.

The shunt currently measures pressure, flow, and occlusion using miniature microelectronics sensors. If device approval comes, the company hopes to move on to developing smart sensors for other organ systems.

DNA-based Drug Testing

Drug and alcohol testing is a controversial topic, partly because of the balance between individual rights to use legal drugs and potential for societal harm if these drugs are abused or if patients transition into illegal drug use and dependence. Inventing technology to determine when, and how much, a person has been drinking or using drugs (including tobacco) would probably increase, rather than decrease, the controversy involved in the topic.

New technology reported recently adds a new element to this discussion. According to Robert Philibert, MD, PhD, Professor of Psychiatry at the University of Iowa and an adjunct faculty member in the Department of Biomedical Engineering, his company’s tests, which rely on epigenetic markers of substance use, could be used, for example, to inform a primary care physician about the actual history of substance use, rather than relying solely on patients’ self-reported use.

Dr. Philibert’s tests are currently pending approval by the Food and Drug Administration. Marketing for the products will begin in the coming weeks.

People and Places

Recognizing the changing priorities in engineering and the growing role of data sciences, Boston University has decided to adapt its curriculum by adding data science requirements for all majors. According to John White, PhD, Chair of the Department of Biomedical Engineering, “Advances in data sciences and computing technology will allow us to make sense of all these data.”

The Biomedical Science Program at Howard Payne University in Brownwood, Texas, has received a $200,000 grant from  the James A. “Buddy” Davidson Charitable Foundation to endow a scholarship in Davidson’s name, as well as to refurbish the program’s Winebrenner Memorial Hall of Science.

Finally, we offer our congratulations this week to James C. Gee, PhD, Professor of Radiologic Science in Radiology at the University of Pennsylvania’s Perelman School of Medicine and a Graduate Group faculty member in Penn’s Department of Bioengineering.  Dr. Gee was named a fellow of the American Institute for Medical and Biological Engineering.

Oncology/Engineering Review Published

oncology
Mike Mitchell, Ph.D.

Michael Mitchell, Ph.D., who will arrive in the Spring 2018 semester as assistant professor in the Department of Bioengineering, is the first author on a new review published in Nature Reviews Cancer on the topic of engineering and the physical sciences and their contributions to oncology. The review was authored with Rakesh K. Jain, Ph.D., who is Andrew Werk Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School, and Robert Langer, Sc.D., who is Institute Professor in Chemical Engineering at the David H. Koch Institute for Integrative Cancer Research at MIT. Dr. Mitchell is currently in his final semester as a postdoctoral fellow at the Koch Institute and is a member of Dr. Langer’s lab at MIT.

The review focuses on four key areas of development for oncology in recent years: the physical microenvironment of the tumor; technological advances in drug delivery; cellular and molecular imaging; and microfluidics and microfabrication. Asked about the review, Dr. Mitchell said, “We’ve seen exponential growth at the interface of engineering and physical sciences over the last decade, specifically through these advances. These novel tools and technologies have not only advanced our fundamental understanding of the basic biology of cancer but also have accelerated the discovery and translation of new cancer therapeutics.”

Week in BioE (October 6, 2017)

We Bleed Green

field goalBiomechanics is a subdiscipline within bioengineering with many applications that include studying how tissue forms and grows during development (see our profile of incoming faculty member Alex Hughes to learn more) and determining how the ‘imprint’ of spine-based pain can be treated with anti-inflammatory medication (see story here on work from the lab of Dr. Beth Winkelstein). Understanding and analyzing human performance are other areas of biomechanics application. On September 24, Eagles kicker Jake Elliott set a team record when he kicked a 61 yard field goal at the end of regulation time to beat the Giants. Marking the achievement, the Philadelphia Inquirer featured an interview with Dr. Chase Pfeifer, a biomedical engineer from the University of Nebraska-Lincoln (UNL), to find out what factors contribute to a successful field goal from this distance. Pfeifer has both knowledge and experience with this question; he was a backup kicker for the Florida State Seminoles as an undergraduate. In the Inquirer, Dr. Pfeifer explained to readers the biophysics behind Elliott’s record kick.

Dr. Pfeifer assures readers that there’s more to kicking a 61-yard field goal than strong muscles. He explains, “The timing of muscle activation was actually more important than muscle strength in achieving that higher foot velocity.” Four muscle groups were activated by Elliott to set his record. In addition, Pfeifer’s colleague at UNL, Professor Tim Gay of the physics department, explained to the Inquirer how the climatic conditions favored Elliott’s success. Specifically, since it was a hot day, the air was less dense, allowing for longer kick distances.

Speaking of football, a new article in Annals of Biomedical Engineering offers some hope for NFL players and the league itself in the wake of growing awareness and concern about chronic traumatic encephalopathy (CTE). The increased focus on CTE has resulted in increased research on the condition and its prevention. Real-time measurement of impact energy in head injuries has, until now, relied on measurements of the motion of the head or helmet, rather than measuring the impact energy directly.

In the Annals article, scientists from Brigham Young University, including David T. Fullwood, Ph.D., professor of mechanical engineering, report on the testing of a new sensor used to measure the impact event. The authors implanted nano-composite foam (NCF) sensors into football helmets and then submitted the helmets to two dozen drop tests. The data collected from the foam sensors were compared to two of the most widely used indices to measure head injury risk, achieving excellent correlation (>90%) with injury risk indicators. The authors intend to test newer models of the sensors in the future, as well as in vivo testing.

Breast Cancer News

Despite significant advances in diagnosis and treatment, breast cancer remains the most common cancer in women. More than 300,000 women are newly diagnosed in the United States each year. Maximizing the effectiveness of treatment involves early detection of the tumor and its metastasis. Imaging plays a key role in this process. However, early tumors are very small, making their detection quite difficult.

In response to this challenge, Zheng-Rong Lu, Ph.D., the M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve University, has coauthored a paper recently published in Nature Communications showing that a newly developed type of molecule could be used for highly sensitive magnetic resonance imaging (MRI) to detect and stratify early breast tumors.

Dr. Lu and his colleagues engineered molecules called fullerenes, which are hollow, spherical molecules of carbon. The team embedded gadolinium, a rare earth metal that is easily detected with MR imaging, into the fullerene to create metallofullerenes. They tested these metallofullerenes both in vitro and in a mouse model to determine how well they enhanced the ability of MRI to detect tumors. Metallofullerene particles could not only distinguish cancers more effectively on MRI, but they could also distinguish more aggressive tumor types from less aggressive ones. In addition, they found that metallofullerenes rapidly cleared from the body via the kidneys, ensuring that these agents would pose minimal toxicity risk. If this technology proves effective in humans, it could significantly improve the early detection of breast cancer and, in turn, survival rates.

One possible risk for breast cancer patients is the metastasis of the cancer to other body regions.  Scientists at Cornell identified a mineral process underlying breast cancer metastasis to bones, reporting their findings in PNAS. Led by Claudia Fischbach-Teschl, Ph.D., associate professor of biomedical engineering at Cornell, the authors investigated how hydroxylapatite — a naturally occurring mineral — participates in metastasis.

Dr. Fischbach-Teschl and her colleagues used X-ray scattering and Raman spectroscopy to examine the nanostructures of hydroxylapatite in the bones of mice with and without breast cancer. They found that bones were more likely to be metastasized by primary breast tumors if the hydroxylapatite crystals in them were less mature. Before the cancer spreads to the bone, the authors found that the cancer “communicates” with these immature crystals, preparing sites in the bone to which the cancer can spread.

With 80% of metastatic breast cancer cases spreading to the bones, the discovery of the Cornell team could contribute enormously to preventing metastasis — not only of breast cancer but also of any cancer with a greater likelihood of spreading to the bones.

A Review of Glucose Monitoring Technology

Our ability to treat diabetes has consistently improved over the years, but the need for patients with the disease to monitor their blood glucose requires either multiple needle pricks or invasive insulin pumps.  However, several technologies are in development around the world to make blood glucose monitoring less cumbersome. In a new article published in Bioengineering, engineers in the United Arab Emirates offer a review of the latest technologies, including analytic methods that could streamline decisions on doses of insulin to offset high glucose levels.

People and Places

The University of California, Davis, opened its Molecular Prototyping and BioInnovation Laboratory (MPBIL) in 2014. Since then, the “biomaker lab” has stood as an example of the future of biotechnology education. In collaboration with UCD’s First-Year Seminar Program, the MPBIL has launched a student-designed pilot course that has thus far yielded three seminars. You can read more about UCD’s innovative program at their Web site.

To promote diversity in engineering, the cosmetics company L’Oréal started the L’Oréal USA For Women in Science Program, which awards Changing the Face of STEM mentoring grants. Among this year’s recipients is John Hopkins University’s Sridevi Sarma, Ph.D. Dr. Sarma, who is an associate professor of biomedical engineering, will use her grant in collaboration with the Girls Scouts of Central Maryland to promote physics education for young women. Congratulations to her!

Burdick Recognized by NIH in Two Programs

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Jason Burdick, Ph.D.

Jason Burdick, Ph.D., professor in the Department of Bioengineering, was among the recent recipients of a grant from Sharing Partnership for Innovative Research in Translation (SPIRiT), a pilot grant program awarded by the Clinical and Translational Science Award (CTSA) division of the National Institutes of Health (NIH).

Dr. Burdick’s research, undertaken with Albert Sinusas, MD, of Yale, concerns the development of a noninvasive treatment to limit the damage to the heart caused by heart attacks, which are suffered annually by almost 750,000 Americans. Using single-photo emission computed tomography (SPECT), the technique identifies the damaged heart muscle on the basis of enzymes activated by damage, followed by the targeted administration of bioengineered hydrogels for the delivery of therapeutics

Dr. Burdick says, “This research has the potential to advance treatments for the many individuals with heart attacks who have few current options. Our approach uses injectable materials and advanced imaging techniques to address the changes in protease levels after heart attacks that can lead to tissue damage.”

In other news, Dr. Burdick was one of 12 researchers named by the NIH’s Center for Engineering Complex Tissues to lead collaborative projects aimed at generating complex tissues for several parts of the body.

Researchers Visualize Resistant Cancer Cells

by Meagan Ita, Ph.D. Student in Bioengineering and GABE Co-President

Cancer is a disease that affects millions, and over the last several decades, researchers have delved deeply into the biological underpinnings of the disease in the hopes of finding a cure. One major discovery is that mistakes in your DNA “instructions” can lead to cancer by crossing the wires in your cellular circuitry, and researchers have developed amazing new drugs that can cause tumors to melt away by targeting these broken components. The problem though is that, most of the time, the tumors come back, and this is a huge barrier to cures.

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Picture of patient treated with vemurafenib and then developing resistance. Courtesy of the American Society of Clinical Oncology

For a long time, everyone assumed that the reason the tumors came back was  DNA mistakes on top of the original mistakes, with these new mistakes blocking the activity of the anti-cancer drug. However, new work led by Sydney Shaffer from the Arjun Raj Lab at Penn Bioengineering, published this week in Nature, challenges this view by looking all the way down at individual cancer cells and seeing how they respond to these drugs on a cell-by-cell basis.

Sydney found that in melanoma, contrary to what researchers thought, it need not be a DNA mistake that leads a cell to become resistant to the drug, but rather a change in cellular identity. Just like your body has cells of all different types, like skin cells and brain cells, cancer cells appear to change between different types, but unlike in the body, cancer cells do it in a seemingly random and uncontrolled way, and the cells exploit this variability to allow those rare cells that have changed their type to survive the drug.

Here, we talk with Sydney about the inspiration, triumphs, and challenges she faced in her research.

What was the initial inspiration for looking at drug resistance in melanoma?

For the first two years of working on this project, we actually didn’t have a clear question in mind. I was just trying a bunch of different experiments with melanoma cells, and I noticed something that we found thought-provoking. Whenever we gave the melanoma cells a particular drug, they would become resistant at exactly the same point in time. At first, this may not seem unusual, but for example, if everyone showed up at a restaurant to eat lunch at exactly noon, you would guess this was not happening purely by chance. Maybe classes let out right beforehand? Or a big meeting? For the melanoma cells, we would similarly expect there to be a range of different times for the cells to become resistant, but instead it all happened at once.

This observation helped us figure out that the drug-resistant cells probably already exist before we treat them. It also got us curious about the particular processes that make the cells resistant, and we spent many lab meetings discussing this observation until one postdoc, Gautham Nair, suggested trying some experiments based upon the classical molecular biology experiments of Luria and Delbrück.

Who were Luria and Delbrück, and how did they influence your work?

Max Delbrück and Salvador Luria (below) were scientists who, in the 1940s, performed a clever experiment that demonstrated that bacteria become resistant to viruses through random DNA mutations. According to Wikipedia, Luria actually had the idea for these experiments while watching slot machines!

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Delbrück (left) and Luria. Courtesy of the Genetics Society of America.

Their experiment was super simple: it was basically a statistical way to see whether cells “sense and respond” to a challenge, or whether they just passively get a mutation that lets some fraction of them survive the challenge, basically like Darwinian evolution. The idea is that, in the first scenario, there is no history: every cell has an equal chance to respond when challenged.

But in the second scenario, history matters in that if your great-grandparent was a survivor, then all your relatives would be too. If you could redo history over and over, then sometimes maybe your great-great-great-great-grandparent would be a survivor, and so you would get a whole bunch of survivors when the challenge came. Luria and Delbrück’s results showed that this second scenario was what happened with bacteria, providing the first evidence for genetic mutations in bacteria occurring in the absence of selection, and they both went on to win a Nobel prize in 1969.

Arjun actually had just lectured about these experiments in our graduate course on modeling biological systems. We adapted the same strategy and theory as Luria and Delbrück’s experiments for our work but applied it to melanoma and actually found a different result. Our experiments showed that resistance in melanoma does not arise through a heritable DNA mutation.

Shaffer colony
Picture of a resistant colony growing in the Raj lab.

Based upon this work, do you have any ideas for how we might prevent resistance in patients?

Yes. The recommended dosing for many of these drugs is daily. Our work would suggest that something like interval therapy might be more effective, for instance, if you gave the drug for a few days, killed many of the tumor cells, and then stopped the drug. During the time that the drug is stopped, the cells that initially survived the drug (we call these cells pre-resistant) could then transition out of this cell state and back to a sensitive state. Then, when the patient takes the drug again, it would be more effective at killing the remaining tumor cells. Another idea would be to find drugs that are specific to the pre-resistant cells and give these drugs in combination with other targeted therapies.

Were there any “Aha!” moments while working on this project?

One of the most exciting moments of this research was when we first found the pre-resistant cells. Hidden among thousands of pictures of empty cells, we were shocked to actually see the rare cells full of brightly tagged resistance genes (below).

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Resistant cells growing in the Raj lab.

What were some low points in working on the project? Do you recall any specific moments that you just felt intellectually and/or emotionally stumped? How did you get through them?

Oh yes, there were definitely low points during this project. One that stands out to me specifically was this one Friday afternoon where I presented at lab meeting. At the time, I only had a little bit of preliminary data. One of the members of the lab asked me a series of questions about resistance: How many different drug doses had I tried? Could I just give a lot and kill them all? What dose of drug is relevant for patients? What about drug resistance? Was I really interested in? All reasonable questions to ask. However, this was really overwhelming to a first-year graduate student because it made me realize that I didn’t have a clearly defined project that I was working on yet. There were just so many different questions that I didn’t know where to start.

Ultimately, with Arjun’s guidance, I came to realize that this was part of the process of figuring out what my thesis project would be, and the vagueness of our ideas at this time was a great thing because it left me open to find a problem that I found really interesting.

At another point in working on this: I remember that we were clearly conceptually stuck. We had identified the rare cells, but it wasn’t clear how to find out if these were the same cells that become resistant to drug. I had an entire lab meeting where we discussed this concern and came to the conclusion that, without some connection between the cells in this state and resistance, the work would be very speculative, which felt unsatisfying to me. Unfortunately, there wasn’t a quick fix to this problem. We just ended up trying a whole bunch of different ideas and eventually one of our strategies worked out.

Were there any funny moments that stand out to you?

Yeah! I was 40 weeks pregnant as we were finishing off our first submission of the paper! As my due date passed, I was really feeling the pressure to finish everything. Each day, I was coming into lab and just hoping I wouldn’t go into labor yet! Actually, the members of our lab had placed bets on when the baby would be born. Fortunately, those who bet on a late arrival ended up winning, and we submitted the paper the day before my daughter, Julien, was born. I was actually still at the hospital when I got the e-mail that the paper went to review.

So even though it might seem like this project is checked off the list with a kick-ass publication, there are probably a bunch of unfinished ideas you have. So,what are you working on next? Will this project ever be “done?”

For sure. The list of unfinished ideas is very long, and some of the questions that came from this work are now being pursued by other people in the lab. Right now, I’m working on ways of measuring the length of time that individual cells remain in these different cell states.

Interested in sharing your research in Penn BE? Contact penngabe@gmail.com for an interview by GABE (Graduate Association of Bioengineers) and let us know!