Week in BioE (July 31, 2018)

New Data Analysis Methods

Like many other fields, biomedical research is experiencing a data explosion. Some estimates suggest that the amount of data generated from the health sciences is now doubling every eighteen months, and experts expect it to double every seventy-three days by 2020.  One challenge that researchers face is how to meaningfully analyze this data tsunami.

The challenge of interpreting data occurs at all scales, and a recent collaboration shows how new approaches can allow us to handle the volumes of data emerging at the level of individual cells to infer more about how biology “works” at this level.  Wharton Statistics Department researchers Mo Huang and Jingshu Wang (PhD Student and Postdoctoral Researcher, respectively) collaborated with Arjun Raj’s lab in Bioengineering and published their findings in recent issues of Nature Methods and Proceedings of the National Academy of Sciences.  One study focused on a de-noising technique called SAVER to provide more precise data from single cell experiments and significantly improves the ability to detect trends in a dataset, similar to how increasing sample size helps improve the ability to determine differences between experimental groups.  The second method, termed DESCEND, creates more accurate characterization of gene expression that occur in individual cells. Together these two methods will improve data collection for biologists and medical professionals working  to diagnose, monitor, and treat diseased cells.

Dr. Raj’s team contributed data to the cause and acted as consultants on the biological aspects of this research. Further collaboration involved Mingyao Li, PhD, Professor of Biostatistics at the Perelman School of Medicine, and Nancy Zhang, PD, Professor Statistics at the Wharton School. “We are so happy to have had the chance to work with Nancy and Mingyao on analyzing single cell data,” said Dr. Raj. “The things they were able to do with our data are pretty amazing and important for the field.”

Advancements in Biomaterials

This blog features many new biomaterials techniques and substances, and there are several exciting new developments to report this week. First, the journal of Nature Biomedical Engineering published a study announcing a new therapy to treat or even eliminate lung infections, such as those acquired while in hospital or as the result of cystic fibrosis, which are highly common and dangerous. Researchers identified and designed viruses to target and kill the bacteria which causes these infections, but the difficulty of administering them to patients has proven prohibitive. This new therapy, developed by researchers at the Georgia Institute of Technology, is administered as a dry powder directly to the lungs and bypasses many of the delivery problems appearing in past treatments. Further research on the safety of this method is required before clinical trials can begin.

A team at Harvard University published another recent study in Nature Biomedical Engineering announcing their creation of a tissue-engineered scale model of the left human heart ventricle. This model is made from degradable fibers that simulate the natural fibers of heart tissue. Lead investigator Professor Kevin Kit Parker, PhD, and his team eventually hope to build specific models culled from patient stem cells to replicate the features of that patient’s heart, complete with the patient’s unique DNA and any heart defects or diseases. This replica would allow researchers and clinicians to study and test various treatments before applying them to a specific patient.

Lastly, researchers at the Tufts University School of Engineering published in the Proceedings of the National Academy of Sciences on their creation of flexible magnetic composites that respond to light. This material is capable of macroscale motion and is extremely flexible, allowing its adaptation into a variety of substances such as sponges, film, and hydrogels. Author and graduate student Meg Li explained that this material differs from similar substances in its complexity; for example, in the ability for engineers to dictate specific movements, such as toward or away from the light source. Co-author Fiorenzo Omenetto, PhD, suggests that with further research, these movements could be controlled at even more specific and detailed levels.

CFPS: Getting Closer to “On Demand” Medicine

A recent and growing trend in medicine is the move towards personalized or “on demand” medicine, allowing for treatment customized to specific patients’ needs and situations. One leading method is Cell-Free Protein Synthesis (CFPS), a way of engineering cellular biology without using actual cells. CFPS is used to make substances such as medicine, vaccines, and chemicals in a sustainable and portable way. One instance if the rapid manufacture of insulin to treat diabetic patients. Given that many clinics most in need of such substances are found in remote and under-served locations far away from well-equipped hospitals and urban infrastructure, the ability to safely and quickly create and transport these vital substances to patients is vitally important.

The biggest limiting factor to CFPS is difficulty of replicating Glycosylation, a complex modification that most proteins undergo. Glycosylation is important for proteins to exert their biological function, and is very difficult to synthetically duplicate. Previously, achieving successful Glycosylation was a key barrier in CFPS. Fortunately, Matthew DeLisa, PhD, the Williams L. Lewis Professor of Engineering at Cornell University and Michael Jewett, PD, Associate Professor of Chemical and Biological Engineering at Northwestern University, have created a “single-pot” glycoprotein biosynthesis that allows them to make these critical molecules very quickly. The full study was recently published in Nature Communications. With this new method, medicine is one step closer to being fully “on demand.”

People and Places

The Institute of Electrical and Electronics Engineers (IEEE) interviewed our own Penn faculty member Danielle Bassett, PhD, the Edwardo D. Glandt Faculty Fellow and Associate Professor in Bioengineering, for their website. Dr. Bassett, who shares a joint appointment with Electrical Systems Engineering (ESE) at Penn, has published groundbreaking research in Network Neuroscience, Complex Systems, and more. In the video interview (below), Dr. Bassett discusses current research trends in neuroscience and their applications in medicine.

Finally, a new partnership between Case Western Reserve University and Cleveland Clinic seeks to promote education and research in biomedical engineering in the Cleveland area. Cleveland Clinic Lerner Research Institute‘s Chair of Biomedical Engineering, Geoff Vince, PhD, sees this as an opportunity to capitalize on the renown of both institutions, building on the region’s already stellar reputation in the field of BME. Dozens of researchers from both institutions will have the opportunity to collaborate in a variety of disciplines and projects. In addition to professional academics and medical doctors, the leaders of this new partnership hope to create an atmosphere that can benefit all levels of education, all the way down to high school students.

Week in BioE (July 25, 2018)

Advances in Stem Cell Research

Stem cell therapy has been used to treat a variety of conditions.

A paper published this month in Scientific Reports announced a new a strategy for the treatment of segmental bone defects. The new technique, called Segmental Additive Tissue Engineering (or SATE) comes from a team of researchers with the New York Stem Cell Foundation Research Institute (NYSCF). A press release from the NYSCF and an accompanying short video (below) describe the breakthrough technique, which will “[allow] researchers to combine segments of bone engineered from stem cells to create large scale, personalized grafts that will enhance treatment for those suffering from bone disease or injury through regenerative medicine.”

Segmental Additive Tissue Engineering from NYSCF on Vimeo.

Ralph Lauren Senior Investigator Guiseppe Maria de Peppo, PhD, and first author Martina Sladkova, PhD, express their hope that this new procedure will help address some of the limitations of bone grafts, such as immune system rejection, the need for growing bones in pediatric patients, and the difficulty of creating larger bone grafts made from patient stem cells.

Elsewhere in stem cell research, the Spanish Agency for Medicines and Medical Devices has given the company Viscofan BioEngineering approval to start clinical trials for stem cell therapy to treat heart failure. Already a world leader in the market for medical collagen, Viscofan is now turning its research toward using collagen (a protein found in the connective tissue of mammals) to strengthen the weakened heart muscle of those with ischemic cardiomyopathy, a type of heart failure and the leading cause of death in the world. This new “Cardiomesh” project includes collaborators from industry, academia, and hospitals to create this elastic and biodegradable product. Viscofan expects to start clinical trials after the summer of this year, and the full details can be found in Viscofan’s press release.

Federal Grant Supports International Bioengineering Research

The Canadian government awarded a $1.65 million federal grant to two top Canadian universities to develop a center based on engineering RNA. The University of Lethbridge and the Université de Sherbrooke will team up with international collaborators from the United States, Germany, France, Australia, and more and to found and develop the Ribonucleic Acid Bioengineering and Innovation Network Collaborative Research and Training Experience over the next six years. This comes as part of the Canadian government’s CREATE initiative, which awards grants to research teams across the country to support research, innovation, and jobs-creation in the sciences. These two universities are national leaders in the field of RNA research, a diverse and interdisciplinary field. This new network will focus on training of both young academics transitioning to industry and entrepreneurs looking to develop new technologies. This project is led by Hans-Joachim Wieden, PhD, Chemistry and Biochemistry faculty at the University of Lethbridge and an Alberta Innovates Strategic Chair in RNA Bioengineering.

Lehigh University Awarded Grant in Ebola Research

Close to Philadelphia in Allentown, PA, researchers at Lehigh University received a National Science Foundation (NSF) grant to support their research into one of the deadliest of modern diseases, the Ebola virus, which is highly infectious and currently without vaccine or cure. Entitled “TIM Protein-Mediated Ebola Virus-Host Cell Adhesion: Experiments and Models,” the goal of this research is to create a “predictive and quantitative model of the Ebola Virus (EBOV)-host cell interactions at the molecular through single-virus levels.” Building on past research, the investigators ultimately hope to provide the first quantitative study of this type of cell interaction. By studying how EBOV enters the body through healthy cells, the aim is to understand how it works and ultimately develop a technique to stop its entry. The lead investigator, Anand Jagota, PhD, is the current Professor and Founding Chair of Lehigh University’s Bioengineering program.

New Research in Brain Tumor Removal

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded a grant to Fake (Frank) Lu, PhD, Assistant Professor of Biomedical Engineering at the State University of New York (SUNY) at Binghamton in support of his research to design more accurate techniques for the removal of brain tumors. His technique, called Stimulated Raman Scattering or SRS, is a mode of identifying molecules during surgery which can be used to create a highly detailed and accurate image. Dr. Lu’s SRS techniques will improve both the speed of the surgery and the accuracy of the tissue removal. With this grant support, Dr. Lu’s team will collaborate with local universities and hospitals on collecting more data as their next step before making the technology more widely available.

People and Places

Undergraduate students at our neighbor Drexel University received the Robert Noyce Scholarship, an NSF program that supports students seeking their teacher certification in science and math at the middle school level. The co-investigators and undergraduates are from a variety of disciplines and programs across the university, including co-investigator Donald L. McEachron, PhD, Teaching Professor of Biomedical Engineering, Science and Health Systems. The students’ curriculum in the DragonsTeach Middle Years program will combine rigorous preparation for teaching STEM subjects and the foundational knowledge to work with under-served schools.

Another group of students, this time from California State University, Long Beach, used their victory in the university’s annual Innovation Challenge as an opportunity to launch a startup called Artemus Labs. Their first product, “Python,” uses body heat other physical sensations to regulate a prosthetic liner, useful in making sure prosthetic limbs are comfortable for the wearer. The students explained that their idea was driven by need, as few prosthetic manufacturers prioritize such factors as temperature or sweat regulation in the creation of their products.

Finally, the University of Southern California Viterbi School of Engineering has a new Chair of Biomedical Engineering: Professor K. Kirk Shung, PhD. Dr. Shung obtained his doctorate from the University of Washington and joined USC in 2002. With a background in electrical engineering, Dr. Shung’s research focuses on high frequency ultrasonic imaging and transducer development, and has been supported by a NIH grant as well as won multiple awards from the American Institute of Ultrasound in Medicine and the Institute of Electrical and Electronics Engineers (IEEE), among others.

Week in BioE (July 9, 2018)

A New Treatment for Joint Dysfunction

TMD is a common condition affecting movement of the jaw

Medical researchers have long been baffled by the need to find safe and effective treatment for a common condition called temporomandibular joint dysfunction (TMD). Affecting around twenty-five percent of the adult population worldwide, TMD appears overwhelmingly in adolescent, premenopausal women. Many different factors such as injury, arthritis, or grinding of the teeth can lead to the disintegration of or damage to the temporomandibular joint (TMJ), which leads to TMD, although the root cause is not always clear. A type of temporomandibular disorder,  TMD can result in chronic pain in the jaw and ears, create difficulty eating and talking, and even cause occasional locking of the joint, making it difficult to open or close one’s mouth.  Surgery is often considered a last resort because the results are often short-lasting or even dangerous.

The state of TMD treatment may change with the publication of a study in Science Translational Medicine. With contributions from researchers at the University of California, Irvine (UCI), UC Davis, and the University of Texas School of Dentistry at Houston, this new study has successfully implanted engineered discs made from rib cartilage cells into a TMJ model. The biological properties of the discs are similar enough to native TMJ cells to more fully reduce further degeneration of the joint as well as potentially pave the way for regeneration of joints with TMD.

Senior author Kyriacos Athanasiou, PhD, Distinguished Professor of Biomedical Engineering at UCI, states the next steps for the team of researchers include a long-term study to ensure ongoing effectiveness and safety of the implants followed by eventual clinical trials. In the long run, this technique may also prove useful and relevant to the treatment of other types of arthritis and joint dysfunction.

Advances in Autism Research

Currently, diagnosis of autism spectrum disorders (ASD) has been limited entirely to clinical observation and examination by medical professionals. This makes the early identification and treatment of ASD difficult as most children cannot be accurately diagnosed until around the age of four, delaying the treatment they might receive. A recent study published in the journal of Bioengineering & Translational Medicine, however, suggests that new blood tests may be able to identify ASD with a high level of accuracy, increasing the early identification that is key to helping autistic children and their families. The researchers, led by Juergen Hahn, PhD, Professor and Department Head of Biomedical Engineering at the Rensselaer Polytechnic Institute, hope that after clinical trials this blood test will become commercially available.

In addition to work that shows methods to detect autism earlier, the most recent issue of Nature Biomedical Engineering includes a study to understand the possible causes of autism and, in turn, develop treatments for the disease. The breakthrough technology of Cas9 enzymes allowed researchers to edit the genome, correcting for symptoms that appeared in mice which resembled autism, including exaggerated and repetitive behaviors. This advance comes from a team at the University of California, Berkeley, which developed the gene-editing technique known as CRISPR-Gold to treat symptoms of ASD by injecting the Cas9 enzyme into the brain without the need for viral delivery. The UC Berkeley researchers suggest in the article’s abstract that these safe gene-editing technologies “may revolutionize the treatment of neurological diseases and the understanding of brain function.” These treatments may have practical benefits for the understanding and treatment of such diverse conditions as addiction and epilepsy as well as ASD.

Penn Professor’s Groundbreaking Bioengineering Technology

Our own D. Kacy Cullen, PhD, was recently featured in Penn Today for his groundbreaking research which has led to the first implantable tissue-engineered brain pathways. This technology could lead to the reversal of certain neurodegenerative disorders, such as Parkinson’s disease.

With three patents, at least eight published papers, $3.3 million in funding, and a productive go with the Penn Center for Innovation’s I-Corps program this past fall, Dr. Cullen is ready to take this project’s findings to the next level with the creation of a brand new startup company: Innervace. “It’s really surreal to think that I’ve been working on this project, this approach, for 10 years now,” he says. “It really was doggedness to just keep pushing in the lab, despite the challenges in getting extramural funding, despite the skepticism of peer reviewers. But we’ve shown that we’re able to do it, and that this is a viable technology.” Several Penn bioengineering students are involved in the research conducted in Dr. Cullen’s lab, including doctoral candidate Laura Struzyna and recent graduate Kate Panzer, who worked in the lab all four years of her undergraduate career.

In addition to his appointment as a Research Associate Professor of Neurosurgery at the Perelman School of Medicine at the University of Pennsylvania, Dr. Cullen also serves as a member of Penn’s Department of Bioengineering Graduate Group Faculty, and will teach the graduate course BE 502 (From Lab to Market Place) for the BE Department this fall 2018 semester. He also serves as the director for the Center of Neurotrauma, Neurodegeneration, and Restoration at the VA Medical Center.

New Prosthetics Will Have the Ability to Feel Pain

New research from the Department of Biomedical Engineering at Johns Hopkins University (JHU) has found a way to address one of the difficult aspects of amputation: the inability for prosthetic limbs to feel. This innovative electronic dermis is worn over the prosthetic, and can detect sensations (such as pain or even a light touch), which are conveyed to the user’s nervous system, closing mimicking skin. The findings of this study were recently published in the journal Science Robotics.

While one might wonder at the value of feeling pain, both researchers and amputees verify that physical sensory reception is important both for the desired realism of the prosthetic or bionic limb, and also to alert the wearer of any potential harm or damage, the same way that heat can remind a person to remove her hand from a hot surface, preventing a potential burn. Professor Nitish Thakor, PhD, and his team hope to make this exciting new technology readily available to amputees.

People and Places

Women are still vastly outnumbered in STEM, making up only twenty percent of the field, and given the need for diversification, researchers, educators, and companies are brainstorming ways to proactively solve this problem by promoting STEM subjects to young women. One current initiative has been spearheaded by GE Healthcare and Milwaukee School of Engineering University (MSOE) who are partnering to give middle school girls access to programs in engineering during their summer break at the MSOE Summer STEM Camp, hoping to reduce the stigma of these subjects for young women. GE Girls also hosts STEM programs with a number of institutions across the U.S.

The National Science Policy Network (NSPN) “works to provide a collaborative resource portal for early-career scientists and engineers involved in science policy, diplomacy, and advocacy.” The NSPN offers platforms and support including grant funding, internships, and competitions. Chaired and led by emerging researchers and professors from around the country, including biomedical engineering PhD student Michaela Rikard of the University of Virginia, the NSPN seeks to provide a network for young scientists in the current political climate in which scientific issues and the very importance of the sciences as a whole are hotly contested and debated by politicians and the public. The NSPN looks to provide a way for scientists to have a voice in policy-making. This new initiative was recently featured in the Scientific American.

Upon its original founding in 2000, the Bill and Melinda Gates Foundation has included the eradication of malaria as part of its mission, pledging around $2 billion to the cause in the years since. One of its most recent initiatives is the funding of a bioengineering project which targets the type of mosquitoes which carry the deadly disease. Engineered mosquitoes (so-called “Friendly Mosquitoes”) would mate in the wild, passing on a mosquito-killing gene to their female offspring (only females bite humans) before they reach maturity. While previous versions of “Friendly Mosquitoes” have been met with success, concerns have been raised about the potential long-term ecological effects to the mosquito population. UK-based partner Oxitec expects to have the new group ready for trials in two years.