The week of August 21-25, 20 students from area middle schools visited Penn to participate in InnoWorks, an educational initiative of the United InnoWorks Academy (UIA), a non-profit organization founded in 2003 by William Hwang, M.D., Ph.D., when he was an undergraduate engineering major at Duke. Today, InnoWorks offers programs at 20 colleges and universities in the U.S. and Caribbean. In the program, undergraduate student volunteers host middle schoolers from disadvantaged backgrounds to foster the teenagers’ interest in science and engineering.
Each day of the week, from 9:15 a.m. to 5:00 p.m., the group of teens attended presentations, conducted experiments, and competed against one another in activities designed to have them apply the principles they learned about. Each day was dedicated to different topics: materials science on Monday; biology on Tuesday; chemistry and earth science on Wednesday; physics and computer science on Thursday; and a wrap-up day on Friday. In addition, over the course of the week, the students were scored for their activities, with a winner announced at the end of the week.
For instance, on Friday, students participating in InnoWorks competed in the Egg Drop Challenge. Using materials provided for them, the students designed their own parachutes for eggs, which they used in dropping the eggs from the second floor of Skirkanich Hall to the ground floor. The students did so well that the competition had to be extended to the third floor.
On another day, Dr. Kushol Gupta, a research assistant professor at Penn conducting research on HIV and assistant director of the Penn Band, talked to the students about the physics of music. Sarah Tang and Monroe Kennedy of Dean Vijay Kumar’s GRASP lab discussed the current state of robotics and drones and showed video clips of some of their work. It was among the most popular popular parts of the week.
Here at Penn, the codirectors of the chapter are Jacqueline Valeri, a senior bioengineering major, and Monica Shen, a senior biology major. Asked about InnoWorks this year, Jackie said, “The InnoWorks program is a great camp to be involved with because the hands-on, interactive engagement really gets our students excited about science. We try to do really minimal lecturing time and maximize the opportunity for the students to actually do experiments, demonstrations, and design challenges. As codirector of this year’s program, it was really awesome to see what a great group of students we had this year and how they flourished throughout the week. This is my third year participating in Penn’s InnoWorks chapter and it has been one of the most rewarding, fun experiences that I’ve had at Penn!”
Since its invention in the early 1970s, magnetic resonance imaging (MRI) has played an increasingly important role in the diagnosis of illness. In addition, over time, the technology of MRI has evolved enormously, with the ability to render more detailed three-dimensional images using stronger magnetic fields . However, imaging tissues under mechanical loads (e.g., beating heart, lung breathing) are still difficult to image precisely with MRI.
A new study in PLOS One, led by Morten Jensen, Ph.D., of the University of Arkansas, breaks an important technical barrier in high resolution imaging for tissues under mechanical load. Using 3D-printed mounting hardware and 7-tesla MRI, this group produced some of the highest quality images yet produced of the mitral valve exposed to physiological pressures (see above). In the longer term, this method could point to new corrective surgical procedures that would greatly improve the repair procedures for mitral valves.
Among the most significant challenges faced by surgical oncologists is developing a ‘clear margin,’ meaning that the tissue remaining after tumor excision is free of any tumor cells. If the margins are not free of tumor cells, the cancer is more likely to recur. However, until now, it has been impossible to determine if cancer cells were still present in tissue margins before finishing surgery because of the time required to test specimens.
At the University of Texas, Austin, however, scientists are getting closer to overcoming this obstacle. In a recent study published in Science Translational Medicine, this team of scientists presents the MasSpecPen — short for mass spectrometry pen. This device is capable of injecting a tiny drop of water into tissue, extracting the water after it mixes with the tissue, and quickly analyzing the sample’s molecular components. The authors, who included biomedical engineering faculty member Thomas E. Milner, Ph.D., tested the device using ex vivo samples from 253 patients with different varieties of cancer, including breast, lung, and thyroid cancers. The MasSpecPen provided sensitivity, specificity, and accuracy exceeding 96% in all cases. Although it has yet to be tested intraoperatively, if effective under those conditions, the device could become an essential part of the surgeon’s arsenal.
If the MasSpecPen could render surgical treatment of cancer more effective, a device developed at SUNY Buffalo could help doctors diagnose lung cancer earlier. Lung cancer is a particularly deadly variety of cancer because patients don’t feel any discomfort until the cancer has spread to other areas of the body. In collaboration with Buffalo’s Roswell Park Center Institute, microchip manufacturer Intel, and local startup Garwood Medical Devices, a team of scientists, including Professor Edward P. Furlani, Ph.D., from Buffalo’s Department of Chemical and Biomedical Engineering, was awarded a grant from the National Science Foundation to develop a subcutaneous implant incorporating a nanoplasmonic biochip to detect biomarkers of lung cancer. A wearable smart band would receive data from the biochip and would act as an early warning system for lung cancer. The biomarkers selected for the biochip would optimally predict lung cancer risk much earlier than the metastasis stage. If the system that the team develops is successful in diagnosing lung cancer before it spreads, it could greatly improve survival and cure rates.
Worldwide but particularly in the Global South, malaria remains a major public health concern. According to a Global Burden of Disease study in 2015, there were nearly 300 million cases of the disease in a single year, with 731,000 fatalities. One of the earliest treatments to combat malaria was invented by British colonialists, who added quinine to the tonic used in the gin and tonic cocktail. More recently the drug artemisinin was developed for fighting malaria. However, this drug and its derivatives are very expensive. The primary reason for this cost is that the drug is extracted from the sweet wormwood plant, which is in short supply. In hopes of producing a greater supply of artemisinin, scientists collaborating among Denmark, Malaysia, and the Netherlands report in Frontiers in Bioengineering and Biotechnology that transplanting the genes responsible for producing atremisinin into Physcomitrella patens, a common moss, led to a much faster production rate of the drug than what is possible with the wormwood plant. The process proved simpler and less expensive than earlier attempts to transplant genes into tobacco plants. If this potential is harnessed correctly, it could make an enormous difference in lessening the global burden of malaria.
We’ve known for years about the flight-or-fight response — the adrenergic response of our bodies to danger, which we share in common with a number of other animals. Once the decision to flee is made, however, we know far less about what determines the escape strategy used. According to Malcolm A. MacIver, professor of biomedical engineering and mechanical engineering in Northwestern University’s McCormick School of Engineering, part of the escape strategy depends on how far away the attacker is. In a paper he coauthored that was published in Current Biology, Dr. MacIver studied threat responses in larval zebrafish and found that a fast-looming stimulus produced either freezing or escape at a shorter interval following the threat perception; when the perceived threat was slow looming, longer latency following the perception of the threat was seen, resulting in a greater variety of types of escape behaviors. While it might seem a giant leap between observing behaviors in fish and higher life forms, the basic mechanism in the “oldest” parts of the brain, from an evolutionary standpoint, are less different than we might think.
People and Places
The University of Maryland has announced that construction on a new building to serve as the home of its Department of Bioengineering will be finished by the end of September. The building is to be named A. James Clark Hall, after a builder, philanthropist, and alumnus of Maryland’s School of Engineering. Further south, George Mason University in Fairfax, Va., has announced that the new chair of its Department of Engineering there will be Michael Buschmann, Ph.D., an alumnus of MIT and faculty member since the 1990s at École Polytechnique in Montreal. Congratulations, Dr. Buschmann!
This past summer, 10 undergraduate from 10 colleges came to Penn for 10 weeks (May 30 to August 4) for the Summer Undergraduate Research Experience (SURE), also known as the Research Experience for Undergraduates (REU). During the program, the students were hosted in the laboratories of faculty in Penn’s Schools of Engineering and Applied Science (including Penn Bioengineering faculty Beth Winkelstein, Dan Huh, and Jason Burdick) and Arts and Sciences and the Perelman School of Medicine. These students were hosted under the aegis of the Center for Engineering MechanoBiology (CEMB), a National Science Foundation-funded collaboration among Penn, Washington University (WashU) in St. Louis, New Jersey Institute of Technology (NJIT), Alabama State University, Bryn Mawr College, Boston University, and the University of Texas at Austin.
The students all worked on individual research projects. At the end of the 10-week term, three abstracts from this research were chosen for presentation at the forthcoming annual meeting of the Biomedical Engineering Society (BMES), which will be held October 11-14 in Phoenix. The three students are Kimberly DeLuca (NJIT), John Durel (Univ. of Virginia), and Olivia Leavitt (Worcester Polytech).
The CEMB Web site at WashU has a nice page up featuring the program and this summer’s students.
Zhiliang Cheng, Ph.D., a research assistant professor in the Department of Bioengineering at the University of Pennsylvania, has received an R01 grant from the National Institute of Neurological Disorders and Stroke to study chronic pain. The grant, which provides nearly $1.7 million over the next five years, will support the work of Dr. Cheng, Bioengineering Professor Andrew Tsourkas, and Vice Provost for Education and Professor Beth Winkelstein, in developing a novel nanotechnology platform for greater effectiveness in radiculopathy treatment.
Based on the idea that phospholipase-A2 (PLA2) enzymes, which modulate inflammation, play an important role in pain due to nerve damage, the group’s research seeks to develop PLA2-responsive multifunctional nanoparticles (PRMNs) that could both deliver anti-inflammatory drugs and magnetic resonance contrast agents to sites of pain so that the molecular mechanisms at work in producing chronic pain can be imaged, as well as allowing for the closer monitoring of treatment.
This research builds on previous findings by Drs. Cheng, Tsourkas, and Winkelstein. In a 2011 paper, Drs. Tsourkas and Winkelstein used superparamagnetic iron oxide nanoparticles to enhance magnetic resonance imaging of neurological injury in a rat model. Based on the theory of reactive oxygen species playing a role in pain following neural trauma, a subsequent paper published in July with Sonia Kartha as first author and Dr. Cheng as a coauthor found that a type of nanoparticle called polymersomes could be used to deploy superoxide dismutase, an antioxidant, to sites of neuropathic pain. The current grant-supported study combines the technologies developed in the previous studies.
“To the best of our knowledge, no studies have sought to combine and/or leverage this aspect of the inflammatory and PLA2 response for developing effective pain treatment. We hypothesize that this theranostic agent, which integrates both diagnostic and therapeutic functions into a single system, offers a unique opportunity and tremendous potential for monitoring and treating patients with direct, clinically translational impact,” Dr. Cheng said.
Each year, the Penn Department of Bioengineering chooses undergraduate students to receive fellowships for summer research. These fellowships, which provide a $3,500 stipend for use over 10 weeks, were endowed by the Abraham Noordergraaf Student Summer Bioengineering Research Fund. Dr. Noordergraaf, who died in 2014, was a founding member and first chair of the Penn BE Department. In keeping with Dr. Noordergraaf’s research focus on the cardiovascular system, fellows with a focus on this system are favored but not exclusively awarded.
The fellows for the summer of 2017 were Brianna Karpowicz, Jacqueline Valeri, and Alejandro Villasmil. Brianna is a junior bioengineering major working in the lab of Professor Yale Cohen. In her research, Brianna worked with Dr. Cohen in the Auditory Research Laboratory, examining the modeling of multisensory perceptual decision making and specifically seeking to better understand the mechanisms underlying the relationship between sensory information and perception.
Alejandro Villasmil, who is a senior bioengineering major working in Professor Beth Winkelstein’s lab, used his Noordergraaf’s grant to study chronic pain in neck injury. To better understand this problem, Alejandro helped to model injury to the facet capsular ligament — one of the structures in the neck — by examining how painful and nonpainful stimuli affected the axonal structure. He found using fluorescence technology that uniaxial tension resulted in axonal changes resulting in pain.
Finally, Jacqueline Valeri is a senior bioengineering major doing research in the lab of Professor Jennifer Phillips-Cremins. In Professor Cremins’s lab, Jackie undertook research on stem cells, specifically examining the question of whether light could be used to control and modulate the fate of these cells — a field called optogenetics. She helped to design two light boxes to stimulate the interaction between two proteins as a first step toward ultimately attempting to control pluripotent stem cells using light, specifically determining what cell lines these stem cells ultimately produce.
At Columbia, a new way of treating lung disease is under development. As reported recently in Science Advances, a Columbia research group, headed by Gordana Vunjak-Novakovic, Ph.D., from the Department of Biomedical Engineering, developed a way to prepare grafted lung tissue for transplantation that could make the process easier. The challenge has been removing the epithelial cells, which ultimately make up the surface of the organ, from potential grafts without damaging the blood vessels. Applying a detergent solution to lung tissue from rats, Dr. Vunjak-Novakovic’s team was able to obtain grafts that could subsequently be used as scaffolds for human pulmonary cells and stem cell-derived lung epithelial cells. Although this approach remains in a very early state, the results here indicate promise for this technology for end-stage lung diseases such as emphysema.
Eliminating Obesity and Diabetes With Injections
You’ve probably heard that there’s an epidemic of obesity in the United States. Obesity carries an enormous health cost because it is linked to a variety of major health complications, including diabetes and heart disease. At a cell level, white fat cells require more energy to work off than brown fat cells. Approaches to fight obesity now include efforts to increase the number of brown fat cells. Scientists at Purdue University might have found a significant shortcut to creating more brown fat cells. By inhibiting the Notch signaling pathway, Meng Deng, Ph.D., of the Weldon School of Biomedical Engineering and his colleagues were able to cause white fat cells to convert into brown cells. Reporting their results in Molecular Therapy, the team used nanoparticles loaded with dibenazapine, a chemical used widely in pharmacology, to treat obese mice with targeted injections of the drug-laden nanoparticles. Results showed that the reduction of white fat in the mice was correlated with improved glucose metabolism and reduced body weight. While it’s not yet time to cancel the gym membership, an easier way to combat obesity could be on the horizon.
Diabetes is a chronic health condition with treatments that include diet management and/or insulin injections. In a new twist on diabetes treatments, scientists at the University of Toronto have shown, in a recent PNAS study, that pancreatic islets cells, which produce insulin, could be injected subcutaneously to reverse diabetes in mice. While the idea of transplanting islets into the pancreas has been investigated for some time, this is the first time that transplants were placed under the skin, far away from the pancreas. Impressively, the modules could be retrieved and reused. If future investigations are successful, these modules could form the basis of a treatment for type 1 (so-called juvenile) diabetes, which is caused by autoimmune destruction of the pancreatic islets.
News from New England
Feng Zhang, Ph.D., associate professor in the Departments of Brain and Cognitive Sciences and of Biological Engineering at MIT, is one of five scientists to receive the Albany Medical Prize in Medicine and Biomedical Research for his work on CRISPR-Cas9 gene editing technology. We offer Dr. Zhang our heartfelt congratulations.
Across the river from Cambridge in Medford, Tufts University has announced that its newly completed Science and Engineering Complex (SEC) will open this semester and will combine classrooms and laboratories — specifically what the developers are calling “lab neighborhoods,” or spaces for collaboration among laboratories working on related research questions. Bruce Panilaitis, Ph.D., a research assistant professor in the Department of Biomedical Engineering, is the director of the SEC, and his department will also have offices there.
Cerebral palsy (CP) remains one of the most common congenital birth defects, affecting 500,000 American newborns per year. Gait disorders from CP are common, and crouch gait — characterized by misdirection and improper bending of the feet, causing excessive knee bending and the appearance of crouching — is among the most difficult to correct.
Researchers at Northern Arizona University recently developed a new exoskeleton to treat crouch gait. In an article published in Science Translational Medicine, Zach Lerner, Ph.D., assistant professor of mechanical engineering and a faculty member with NAU’s Center for Bioengineering Innovation, tested a robotic, motorized exoskeleton in seven patients with crouch gait. Six of the seven participants using the exoskeleton show improvements on par with surgical procedures to correct crouch gait. Although commercial availability of the exoskeleton will require testing in much larger patient groups, the device is an encouraging development in the treatment of a difficult disorder.
Brain Science News
A couple of weeks ago, we discussed here how the Department of Defense supports research using electrical stimulation of the scalp to direct brain activity. At the University of Texas at Arlington (UTA), bioengineering professor Hanli Liu, Ph.D., received a NIH grant to test how infrared light, rather than electrical stimulation, can achieve similar effects on the brain. In collaboration with two other UTA professors, Professor Liu uses Transcranial Infrafred Brain Stimulation (TIBS) to project infrared light onto the forehead to enhance blood flow and oxygen supply to the underlying area of the brain. With the grant, she and her colleagues intend to develop imaging tools that will provide greater insight into how both TIBS and the brain itself work.
Even as we learn more about the brain, the devastating effects of neurodegenerative diseases show us how much we still don’t know. Certain drugs can slow the inevitable advance of the disease, but beginning treatment early is important to maintaining a sense of normalcy. At Case Western Reserve University, Anant Madabhushi, Ph.D., professor of biomedical engineering, is developing computer technology to distinguish Alzheimer’s from other disorders and to predict onset earlier and more accurately. Reporting their outcomes in Scientific Reports from testing in nearly 150 patients, Dr. Madabhushi and his colleagues used a variety of clinical measures (blood biomarkers, imaging data, neuropsychological testing) instead of a single test and developed a much more accurate test for detecting Alzheimer’s disease. Their approach, called cascaded multiview canonical correlation (CaMCCo), used the ordered analysis of different tests to stratify different patient groups at each stage, rather than developing a single combined measure all at once. More work will be needed to determine how this approach can lead to earlier detection of Alzheimer’s, but its accuracy is very encouraging for future studies.
Causes for Congratulations
Rose-Hulman Institute of Technology has announced that Kay C. Dee, Ph.D., is among the recipients of this year’s Inspiring Leaders in STEM Award from Insight Into Diversity magazine. Professor Dee, Associate Dean of Learning and Technology and Professor of Biology and Biomedical Engineering at Rose-Hulman, is the former head of her department. As a dean, she has focused on several issues, including easier access for students with disabilities. Congratulations to Dr. Dee!
Also, several bioengineering and biomedical engineering departments across the country are celebrating birthdays. The departments at both the University of Virginia (biomedical engineering) and the University of Michigan (bioengineering) are 50 years old, with Michigan also celebrating the 20th birthday of their biomedical engineering department. The comparative baby of the group, the Department of Biomedical Engineering at Tulane University, turns 40. Happy birthday all!
The roundworm C. elegans is one of the most important model organisms in biological research. With a transparent, millimeter-long body containing only about a thousand cells and a lifespan of a few weeks, there is no better way of deciphering the role of a given gene on a living creature’s anatomy or behavior. In addition, many of the genes discovered in the worm have been shown to have similar roles in other animals and humans.
In the era of big data, however, a single worm isn’t enough. Thousands upon thousands of individual organisms are necessary to compare many different genes and ensure the reliability of experimental results.
Engineers at the University of Pennsylvania have taken strides to make this type of high-throughput experiment feasible by developing a system they have dubbed “the WorMotel.” To demonstrate its effectiveness, the researchers have studied the role of a set of mutations and stress-inducing drugs on the aging of 1,935 of these organisms, specifically, what percentage of their lifespans they remain healthy and active.
The WorMotel system features index-card-sized plates made out of a transparent polymer. Each plate features 240 individual wells, in which a single worm lives its entire life. Automated systems keep them fed and stimulated while machine vision algorithms track and record their behavior.
The WorMotel system is also designed to be highly scalable. Robotic carousels can automatically swap hundreds of WorMotel plates in and out of analysis chambers, studying up to 57,600 worms in a single experiment.
The study, published in the journal eLife, was led by Christopher Fang-Yen, Wilf Family Term Assistant Professor in Bioengineering in Penn’s School of Engineering and Applied Science, and Matthew Churgin, a former graduate student (now a postdoctoral fellow) in his lab. They collaborated with David Raizen, an Associate Professor of Neurology in Penn’s Perelman School of Medicine. Former Fang-Yen lab members Sang-Kyu Jung, Chih-Chieh (Jay) Yu, and Xiangmei Chen also contributed to the research.
Continuing with our series of interviews with new faculty members, we feature this interview with Dr. Joel Boerckel, who has a dual appointment in the Department of Bioengineering at Penn and the Perelman School of Medicine’s Department of Orthopaedic Surgery. Dr. Boerckel’s research concerns the mechanobiology of development and regeneration. Here, he speaks with Andrew Mathis about his career to this point and where he sees the fields of tissue engineering and regenerative medicine heading over the future. Enjoy!
Excessive exposure to the sun remains a leading cause of skin cancers. The common methods of protection, including sunscreens and clothing, are the main ways in which people practice prevention. Amazingly, new research shows that what we eat could affect our cancer risk from sun exposure as well. Joseph S. Takahashi, Ph.D., who is chair of the Department of Neuroscience at the University of Texas Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, was one of a team of scientists who recently published a paper in Cell Reports that found that by restricting the times when animals ate, their relative risk from exposure to ultraviolet light could change dramatically.
We tend to think of circadian rhythms as being among the reasons why we get sleepy at night, but the skin has a circadian clock as well, and this clock regulates the expression of certain genes by the epidermis, the visible outermost layer of the skin. The Cell Reports study found that food intake also affected these changes in gene expression. Restricting the eating to time windows throughout a 24h cycle, rather than providing food all the time, led to reduced levels of a skin enzyme that repairs damaged DNA — the underlying cause of sun-induced skin cancer. The study was conducted in mice, so no firm conclusions about the effects in humans can be drawn yet, but avoiding midnight snacks could be beneficial to more than your weight.
Let’s Get Small
Nanotechnology is one of the most common buzzwords nowadays in engineering, and the possible applications in health are enormous. For example, using tiny particles to interfere with the cancer signaling could give us a tool to stop cancer progression far earlier than what is possible today. One of the most recent approaches is the use of star-shaped gold particles — gold nanostars — in combination with an antibody-based therapy to treat cancer.
The study authors, led by Tuan Vo-Dinh, Ph.D., the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering at Duke, combined the gold nanostars with anti-PD-L1 antibodies. The antibodies target a protein that is expressed in a variety of cancer types. Focusing a laser on the gold nanostars heats up the particles, destroying the cancer cells bound to the nanoparticles. Unlike past nanoparticle designs, the star shape concentrate the energy from the laser at their tips, thus requiring less exposure to the laser. Studies using the nanostar technology in mice showed a significant improvement in the cure rate from primary and metastatic tumors, and a resistance to cancer when it was reintroduced months later.
Nanotechnology is not the only new frontier for cancer therapies. One very interesting area is using plant viruses as a platform to attack cancers. Plant viruses stimulate a natural response to fight tumor progression, and these are viewed by some as ‘nature’s nanoparticles’. The viruses are complex structures, and offer the possibility of genetic manipulation to make them even more effective in the future. At Case Western Reserve University, scientists led by Nicole Steinmetz, Ph.D., associate professor of biomedical engineering, used a virus that normally affects potatoes to deliver cancer drugs in mice. Reporting their findings in Nano Letters, the authors used potato virus X (PVX) to form nanoparticles that they injected into the tumors of mice with melanoma, alongside a widely used chemotherapy drug, doxorubicin. Tumor progression was halted. Most importantly, the co-administration of drug and virus was more effective than packing the drug in the virus before injection. This co-administration approach is different than past studies that focus on packaging the drug into the nanoparticle first, and represents an important shift in the field.
Educating Engineers “Humanely”
Engineering curricula are nothing if not rigorous, and that level of rigor doesn’t leave much room for education in the humanities and social sciences. However, at Wake Forest University, an initiative led by founding dean of engineering Olga Pierrakos, Ph.D., will have 50 undergraduate engineering students enrolled in a new program at the college’s Downtown campus in Winston-Salem, N.C. The new curriculum plans for an equal distribution of general education/free electives relative to engineering coursework, with the expectation that the expansion of the liberal arts into and engineering degree will develop students with a broader perspective on how engineering can shape society.
People in the News
At the University of Illinois, Urbana-Champaign, Rashid Bashir, Ph.D., Grainger Distinguished Chair in Engineering and professor in the Department of Bioengineering, has been elevated to the position of executive associate dean and chief diversity officer at UIUC’s new Carle Illinois College of Medicine. The position began last week. Professor Michael Insana, Ph.D., replaces Dr. Bashir as department chair.
At the University of Virginia, Jeffrey W. Holmes, Ph.D., professor of biomedical engineering and medicine, will serve as the director of a new Center for Engineering in Medicine (CEM). The center is to be built using $10 million in funding over the next five years. The goal of the center is to increase the collaborations among engineers, physicians, nursing professionals, and biomedical scientists.