Speaker: Xiling Shen, Ph.D.
Hawkins Family Associate Professor
Biomedical Engineering
Duke University
Date: Thursday, April 15, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Abstract:
Bodily cells undergo transformations in space and time during development, disease progression, and therapeutic treatment. A holistic approach that combines engineering tools, patient-derived models, and analytical methods is needed to map cellular reprogramming and expose new therapeutic opportunities. The talk will cover our effort across the entire spectrum from bench to bedside, including organogenesis during embryonic development, epigenetic and metabolic reprogramming of cancer metastasis and COVID-19 patients, and organoid technology to guide precision- and immune-oncology.
Xiling Shen Bio:
Dr. Shen is the Hawkins Family Associate Professor in the Department of Biomedical Engineering at Duke University. He is also the director of the Woo Center for Big Data and Precision Health. He received his BS, MS, and PhD degrees from Stanford University and the NSF career award at Cornell University. He is the steering committee chair of the NCI Patient-Derived Model of Cancer Consortium. His lab studies precision medicine from a systems biology perspective. Areas of interests include cancer, stem cells, the but-brain axis, and infectious diseases.
Speaker: Kyle Daniels, Ph.D.
Postdoctoral Scholar, Cellular Molecular Pharmacology
University of California, San Francisco
Date: Thursday, October 22, 2020
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Title: “High-throughput Screening of a Combinatorial CAR Co-stimulatory Domain Library”
Abstract:
CAR T cells—T cells engineered to express a chimeric antigen receptor that redirects their function to a specific antigen—have proven to be an effective therapy for certain B cell cancers, but many issues remain in order to apply CAR T cells to a broader range of cancers. The activity of CAR T cells can be modulated by varying their co-stimulatory domains. Most CARs use co-stimulatory domains from natural proteins such as 41BB or CD28, each of which contains motifs that recruit unique signaling molecules and elicit a corresponding T cell response. One strategy to achieve increased control over T cell function is to engineer synthetic co-stimulatory domains composed of novel combinations of motifs from natural co-stimulatory proteins. We constructed libraries of CARs containing synthetic co-stimulatory domains and screened these library in primary human T cells for the ability to promote proliferation, degranulation, and memory formation. The results of the screens give insights into how signaling motifs dictate cell function and offer clues on how to engineer co-stimulatory domains that promote desired CAR T cell functions.
Bio:
Kyle completed his BS in Biochemistry at University of Maryland-College Park, and did undergraduate research in the lab of Dorothy Beckett where he studied ligand binding to biotin protein ligases. He did his graduate work at Duke University with Terry Oas working to understand the mechanism of coupled binding and folding in the protein subunit of B. subtilis RNase P. He is currently a postdoctoral fellow in Wendell Lim’s lab at UCSF studying how combinations of linear motifs in receptors dictate cell function. He was an HHMI undergraduate researcher, an NSF graduate research fellow, and a Damon Runyon Cancer Research Foundation postdoctoral fellow. His research interests include synthetic biology, how cells process information and make decisions, and cellular therapy. Outside of lab, he enjoys swimming, videogames, and quality time with friends.
See the full list of upcoming Penn Bioengineering fall seminars here.
Innovations in Vascularization Could Lead to a New Future in Bioprinting
We may be one step closer to 3D-printing organs for transplants thanks to innovations in vascularization from researchers at Rice University and Washington University. Jordan Miller, Ph.D., a Penn Bioengineering alumnus, now an assistant professor of bioengineering at Rice, worked with his colleague Kelly Stevens, Ph.D., an assistant professor of the bioengineering department at Washington, to develop 3D-printed networks that mimicked the vascularized pathways for the transport of blood, lymph, and other fluids in the body. Their work appeared on a recent cover of Science, featuring a visual representation of the 3D-printed vessels in vasculature meant to mirror that of the human lung.
Relying heavily on open source 3D-printing, Miller and Stevens, along with collaborators from a handful of other institutions and start-ups, found ways to model dynamic vasculature systems similar to heart valves, airways systems, and bile ducts to keep 3D-printed tissue viable. The video below demonstrates the way the team successfully modeled vasculature in a small portion of the lung by designing a net-like structure around a sack of air. But Miller, a long-time supporter of open source printing and bioprinting, hopes that this is merely one step closer to what he sees as the ultimate goal of allowing for all organs to be bioprinted. Having that sort of power would reduce the complex issues that come with organ transplants, from organ availability to compatibility, and bring an end to a health issue that affects the over 100,000 people on the organ transplant waiting list.
A Combination of Protein Synthesis and Spectrometry Improve Cell Engineering
One goal of modern medicine is to create individualized therapeutics by figuring out a way to control cell function to perform specific tasks for the body without disrupting normal cell function. Balancing these two goals often proves to be one of the greatest difficulties of this endeavor in the lab, but researchers at Northwestern University found a way to combine the two functions at once in methods they’re calling cell-free protein synthesis and self-assembled monolayer desorption ionization (SAMDI) mass spectrometry. This innovation in the combination of the two methods accelerates the trial and error process that comes with engineering cells for a specific need, allowing researchers to cover a lot more ground in determining what works best in a smaller amount of time.
Leading the study are Milan Mrksich, Ph.D., a Henry Wade Rogers Professor of Biomedical Engineering at Northwestern, and Michael Jewett, Ph.D., a Charles Deering McCormick Professor of Teaching Excellence and co-director of the Center for Synthetic Biology at Northwestern. Together, they hope to continue to take advantage of the factory-like qualities of cell operations in order to use cells from any organisms to our advantage as needed. By helping to reduce the amount of time spent on trial and error, this study brings us one step closer to a world of efficient and individualized medicine.
Non-Invasive Sensory Stimulation as New Way of Treating Alzheimer’s
What if we could reduce the effects of Alzheimer’s disease with a non-invasive therapy comprised of only sensory inputs of light and sound? A recent study between Georgia Tech and MIT tries to make that possible. Alzheimer’s patients often have a larger than normal number of amyloid plaques in their brains, which is a naturally occurring protein that in excess can disrupt neurological function. The treatment — designed in part by Abigail Paulson, a graduate student in the lab of Annabelle Singer, Ph.D., assistant professor of Biomedical Engineering at Georgia Tech and Emory University — uses a combination of light and sound to induce gamma oscillations in brain waves of mice with high amounts of these amyloid plaques. Another lead author of the study is Anthony Martorell, a graduate student in the Tsai Lab at MIT, where Singer was a postdoctoral researcher.
This new approach is different from other non-invasive brain therapies for memory improvement, as tests demonstrated that it had the power to not only reach the visual cortex, but that it also had an effect on the memory centers in the hippocampus. An innovation like this could bring about a more widespread form of treatment for Alzheimer’s patients, as the lack of a need for surgery makes it far more accessible. Singer hopes to continue the project in the future by looking at how these sensory stimulations affect the brain throughout a variety of processes, and more importantly, if the therapy can be successfully applied to human patients.
NIH Grant Awarded to Marquette Biomedical Engineering Professor for Metal Artifact Reduction Techniques in CT Scans
Taly Gilat-Shmidt, Ph.D., an associate professor of biomedical engineering at Marquette University, recently received a $1.4 million grant from the National Institute of Health to improve methods for radiation treatment through metal artifact reduction techniques. When patients have some sort of metal that can’t be removed, such as an orthopaedic implant like a hip or knee replacement, it can interfere with the imaging process for CT scans and lead to inaccuracies by obscuring some tissue in the final images. These inaccuracies can lead to difficulty in devising treatment plans for patients who require radiation, as CT scans are often used to assess patients and determine which line of treatment is most appropriate. Gilat-Schmidt hopes to use the grant to implement tested algorithms to help reduce this variability in imaging that comes from metal implants.
People and Places
Activities for Community Education in Science (ACES), founded by Penn chemistry graduate students in 2014, aims to inspire interest and provide a positive outlook in STEM for kids and their families. The biannual event provides students grades 3–8 with an afternoon of demonstrations, experiments, and hands-on activities focused on physics and chemistry.
After an explosive opening demonstration, more than 70 students made their way between experiments in small groups, each participating in different experiments based on their age.
The Society of Women Engineers (SWE) is a non-profit organization serving as one of the world’s largest advocates for women in engineering and technology over the past six decades. With a mission to empower women to become the next leading engineers of the world, SWE is just one of many agents hoping to bring more diversity to the field. Our chapter of SWE at Penn focuses particularly on professional development, local educational outreach, and social activities across all general body members. In a new article from SWE Magazine, the organization collected social media responses from the public on the women engineers we should all know. With a diverse list of engineers from both the past and present, the article helps bring to light just how much even a handful of women contributed to the field of engineering already.
When cells move throughout the body, they do so by dragging themselves, using molecular “arms” to pull themselves closer to where they need to be while unlatching themselves from the area they’re moving away from. In a recent study, Penn Engineers looked at a few mechanobiological factors that help regulate cells’ migration towards their destination, providing new insight into the gene expression feedback loops that keep them from getting stuck.
Joel Boerckel and Devon Mason
The research was led by Joel Boerckel, Assistant Professor of Orthopaedic Surgery in the Perelman School of Medicine and in Bioengineering in Penn Engineering, and bioengineering graduate student Devon Mason. Co-authors include bioengineering graduate student Joseph Collins and researchers from the University of Notre Dame, Indiana University and Purdue University.
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 ScienceRobotics.
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.
Pain is the body’s way of telling you there’s something wrong. For most of us, the pain goes away after the body fixes itself. However, more than 10% of Americans suffer from chronic pain after the healing period. Many chronic pain patients need drugs to reduce their symptoms. Given the pervasive use of opioid drugs to treat chronic pain, opioid addiction is common among chronic pain patients.
However, a remarkably clever and elegant cellular engineering technology may provide a new approach for treating chronic pain. Martin Fussenegger, Ph.D., a professor in the Department of Biosystems Science and Bioengineering at the Swiss Federal Institute of Technology, is the lead author of a new study published in Nature Biomedical Engineering combining cellular and genetic engineering to alleviate pain using cells as factories to produce spearmint. The strategy employed by the authors used engineered human cells to express huwentoxin IV, a blocker of sodium channels regulating pain signals in neurons, upon exposure to carvone, a terpenoid found in spearmint.
Testing their concept in a mouse model of pain, the authors found that mice exposed to spearmint both orally and via aromatherapy showed fewer signs of pain. Looking forward, Dr. Fussenegger and his colleagues believe that their technology, called AromaCell, should be tested next in human cell lines to alleviate concerns about immunological responses to the cells when implanted into patients.
Press Button to Bleed
Another recent article in Nature Biomedical Engineeringdetails the work of the Boston-area biotech firm Seventh Sense Biosystems on their push-button blood collection device, called TAP. As we have discussed here before, currently used blood-drawing procedures are often uncomfortable to patients because of the sharp needle prick used to collect blood. TAP was designed to collect 100 microliters of whole blood using a device the size of a stethoscope bell in a “virtually painless” manner.
The scientists from Seventh Sense designed the patch using microneedle technology. With this approach, they designed TAP with multiple microneedles deployed at high velocity to collect blood from capillaries — the tiniest vessels that connect veins and arteries and that lie closest to the surface of the skin — rather than from a vein tied off with a tourniquet. Testing the device in 144 volunteers, the study authors found that the device was as accurate as current methods for obtaining blood to measure hemoglobin (important for diabetics) and was significantly less painful.
Seventh Sense predicts this disposable device will cost only $5 per use, but this is still almost double the materials cost for standard blood draws. However, the company believes that the pain-free nature of and time saved with TAP will offset the higher cost of the device.
Advances in Global Health
The positively epidemic nature of human papilloma virus (HPV), affecting nearly one quarter of all Americans, has drawn particular attention over the last decade or so. The clear association between HPV and cervical cancer (as well as head and neck cancers) has led to the development and deployment of vaccines (controversial due to the sexually transmitted nature of HPV) and to increased calls for more regular and accurate screening. In developing nations, implementing either effective vaccination or early screening programs remains an uphill struggle.
Responding to the need for more accessible screening technologies, Jessica Ramella-Roman, Ph.D., Associate Professor of Biomedical Engineering at Florida International University (FIU), and Purnima Madhivanan, Ph.D., an epidemiology professor at FIU, traveled to Mysore, India, to install a device developed by Dr. Ramella-Roman at the Public Health Research Institute of India. The device is a hand-held imaging tool that uses a technology called Mueller matrix imaging to provide high-resolution digital images of the cervix in about 5 seconds. The resolution of the images eliminates the need to use dyes or stains to detect malignant cells. The testing of the device is currently ongoing.
Elsewhere in global health, researchers at Google have teamed with medical faculty from Stanford to produce a machine learning algorithm that could examine the human retina and determine whether the person in question is at risk for cardiovascular disease. They report their findings in Nature Biomedical Engineering.
The technology is not ready for actual patients yet — the study authors concede that the algorithm does not outperform the currently available technologies. However, if improved with additional research and testing, the algorithm could be deployed virtually anywhere, including in patients’ homes.
People and Places
Yale University has launched a new Center for Biomedical Data Science, dedicated to collecting, studying, and managing big data. The interim directors are Mark Gerstein, Ph.D., Albert L Williams Professor of Biomedical Informatics, Molecular Biophysics, and Biochemistry, and Hongyu Zhao, Ph.D., Ira V. Hiscock Professor of Biostatistics and Professor of Genetics and Professor of Statistics and Data Science.
The University of Virginia has announced a partnership with Smithfield Bioscience, a subsidiary of Smithfield Foods, Inc. The goal of the partnership is to advance a variety of tissue engineering applications using tissue samples from pigs. George J. Christ, Ph.D., Professor of Biomedical Engineering and Orthopaedic Surgery, heads UVA’s $3 million Center for Advanced Biomanufacturing, which is involved in the partnership.
Finally, we offer our congratulations to Guoqiang Yu, Ph.D., Professor of Biomedical Engineering at the University of Kentucky and a former research faculty member in physics here at Penn, for being awarded a two-year $420,000 R21 research grant from the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Yu will use the money to develop a device to measure cerebral hemodynamics in neonatal ICU patients.
George H.W. Bush refused to eat it, but maybe he should start. It turns out that broccoli, combined with bioengineered yogurt, could provide effect cancer prevention. We’ve known for some time that compounds in certain fresh vegetables can increase chemoprevention, but the levels are usually too low to be effective, or they can’t be assimilated optimally by the body. However, scientists in Singapore found that engineered bacteria, when ingested by mice with colorectal cancer, had anticancer effects. The bacteria caused the secretion of an enzyme by the cancer cells that transformed glucosinolates — compounds found in vegetables — into molecules with anticancer efficacy. The scientists report their findings in Nature Biomedical Engineering.
The authors programmed an E. coli cell line to bind to heparan sulfate proteoglycan, a cell surface protein that occurs in colorectal cancer cells. Once the engineered bacteria bound to the cancer cells, the bacteria secreted myrosinase, an enzyme that commonly occurs in many plants to defend them against aphids. In the cell model employed by the authors, myrosinase caused the conversion of glucosinolates into sulforaphane, which in turn could inhibit cancer cell growth.
The scientists then applied their system in a mouse model of colorectal cancer, feeding the mice yogurt infused with the engineered bacteria. They found that the mice fed broccoli plus the yogurt developed fewer and smaller tumors than mice fed broccoli alone. Additional testing is necessary, of course, but the study authors believe that their engineered bacteria could be used both as a preventive tool in high-risk patients and as a supplement for cancer patients after surgery to remove their tumors.
The Gates of CRISPR
About two years ago, software giant Microsoft unveiled Azimuth, a gene-editing tool for CRISPR/Casa9 that it had developed in collaboration with scientists at the Broad Institute. Now, in response to concerns that CRIPR may edit more of the genome than a bioengineer wants, the team has introduced a tool called Elevation. A new article in Nature Biomedical Engineering discusses the new tool.
In the article, the team, co-led by John C. Doench, Ph.D., Institute Scientist at the Broad Institute, describes how it developed Azimuth and Elevation, both of which are machine learning models, and deployed the tools to compare their ability to predict off-target editing with the ability of other approaches. The Elevation model outperformed the other methods. In addition, the team has implemented a cloud-based service for end-to-end RNA design, which should alleviate some of the time and resource handicaps that scientists face in using CRISPR.
Reducing Infant Mortality With an App
Among the challenges still faced in the developing world with regard to health care is high infant mortality, with the most common cause being perinatal asphyxia, or lack of oxygen reaching the infant during delivery. In response, Nigerian graduate student Charles C. Onu, a Master’s student in the computer science lab of Doina Precup, Ph.D., at McGill University in Montreal, founded a company called Ubenwa, an Igbo word that means “baby’s cry.”
With Ubenwa and scientists from McGill, Onu developed a smartphone app and a wearable that apply machine learning to instantly diagnose birth asphyxia based on the sound of a baby’s cry. In initial testing, the device performed well, with sensitivity of more than 86% and specificity of more than 89%. You can read more about the development and testing of Ubenwa at Arxiv.
People and Places
Several universities have announced that they are introducing new centers for research in bioengineering. Purdue University secured $27 million in funding from Semiconductor Research Corp. for its Center for Brain-inspired Computing Enabling Autonomous Intelligence, or C-BRIC, which opened last month. The center will develop, among other technologies, robotics that can operate without human intervention.
In Atlanta, Emory University received a $400 million pledge from the Robert W. Woodruff Foundation for two new centers — the Winship Cancer Institute Tower and a new Health Sciences Research Building. The latter will host five research teams, including one specializing in biomedical engineering. Further north in Richmond, Virginia Commonwealth University announced that it will begin construction on a new $92 million Engineering Research Building in the fall. The uppermost floors of the new building will include labs for the college’s Department of Biomedical Engineering.
Finally, North Carolina’s Elon College will introduce a bachelor’s degree program in engineering in the fall. The program will offer concentrations in biomedical engineering and computer engineering. Sirena Hargrove-Leak, Ph.D., is director of the program.
Small intestinal mucosa infested with Giardia lamblia parasites
Diseases of the small intestine, including Crohn’s disease and microbial infections, impose a huge burden on health. However, finding treatments for these diseases is challenged by the lack of optimal models for studying disease. Animal models are only so close to human disease states, and laboratory models using cell lines do not completely mimic the environment inside the gut.
However, these limitations might be overcome soon thanks to the research of scientists at Tufts University. In an article recently published in PLOS ONE, a team led by David L. Kaplan, Ph.D., of the Tufts Department of Biomedical Engineering, describes how they used donor stem cells and a compartmentalized biomimetic scaffold to model and generate small intestine cells that could differentiate into the broad variety of cell types common to that organ.
The study team tested the response of its cell model to E. coli, a common pathogen. At the genetic level, the model matched the reaction of the human small intestine when exposed to this bacterium. The success of the model could translate into its use in the near future to better understand the digestive system’s response to infection, as well as to test individualized treatments for inflammatory bowel diseases such as Crohn’s.
Saving Battle-wounded Eyes
The increase in combat survival rates has led to a higher incidence of veterans with permanent vision loss due to catastrophic damage to the eye. Globe injuries will recover of some vision, if caught in time. However, combat care for eye injuries often occurs hundreds or thousands of miles away from emergency rooms with attending ophthalmologists. With this unavoidable delay in treatment, people with globe injuries suffer blindness and often enucleation.
However, battle medics might soon have something in their arsenals to prevent such blinding injuries immediately in the combat theater. As reported recently in Science Translational Medicine, engineers at the University of Southern California (USC) and ophthalmologists from USC’s Roski Eye Institute have collaborated in creating a new material for temporary sealing of globe injuries. The study authors, led by John J. Whalen, III, Ph.D., used a gel called poly(N-isopropylacrylamide) (PNIPAM), already under investigation for treating retinal injuries. PNIPAM is a thermoresponsive sealant, meaning it is a liquid at cooler temperature but an adhesive gel at warmer temperature. These interesting properties mean PNIPAM can be applied as a liquid and then solidifies quickly on the eye. The authors manipulated PNIPAM chemically to make it more stable at body temperature. As envisioned, the gel, when used with globe injuries, could be applied by medics and then removed with cold water just before the eye is treated.
The study team has tested the gel in rabbits, where it showed statistically significant improvement in wound sealing and no negative effects on the eyes or overall health of the rabbits. The authors believe the material will be ready for human testing in 2019.
Predicting Seizures in Epilepsy
Epilepsy is a central nervous system disorder characterized by seizure activity that can range in severity from mild to debilitating. Many patients with epilepsy experience adequate control of seizures with medications; however, about a third of epileptic patients have intractable cases requiring surgery or other invasive procedures.
In what could be a breakthrough in the treatment of refractive epilepsy, scientists from Australia in collaboration with IBM Research-Australia have used big data from epilepsy patients to develop a computer model that can predict when seizures will occur. So far, the technology predicts 69% of seizures in patients. While it’s still short of a range of accuracy making it feasible for use in patients outside of experimental settings, the acquisition of ever-increasing amounts of data will render the model more accurately.
The Art of Genetic Engineering
Among the techniques used in genetic engineering is protein folding, which is one of the naturally occurring processes that DNA undergoes as it takes on three dimensions. Among the major developments in genetic engineering was the discovery of the ability to fold DNA strands artificially, in a process called DNA origami.
Now, as suggested by the name “origami,” some people have begun using the process in quasi-artistic fashion. In an article recently published in Nature, bioengineers at CalTech led by Lulu Qian, Ph.D., assistant professor of bioengineering, showed they were able to produce a variety of shapes and designs using DNA origami, including a nanoscale replica of Leonardo da Vinci’s Mona Lisa.
DNA now also has another unique artistic application — tattoos, although people’s opinions of whether tattooing constitutes art might vary. Edith Mathiowitz, Ph.D., of Brown University’s Center for Biomedical Engineering, is among the patenters of Everence, a technology that takes DNA provided by a customer and incorporates it into tattoo ink. Potential tattooees can now have the DNA of loved ones incorporated into their bodies permanently, if they should so wish.
People and Places
The University of Washington has launched its new Institute for Nano-engineered Systems, cutting the ribbon on the building on December 4. The center will house facilities dedicated to scalable nanomanufacturing and integrated photonics, among others. Meanwhile, at the University of Chicago, Rama Ranganathan, M.D., Ph.D., a professor in the Department of Biochemistry and Molecular Biology and the Institute for Molecular Engineering, will lead that college’s new Center for Physics of Evolving Systems. Congratulations!
Repairing heart tissue after a heart attack is a major focus of tissue engineering. A key challenge here is keeping grafted cardiomyocytes in place within the tissue to promote repair. As we reported a couple of weeks ago, using tissue spheroids and nanowires is one approach to overcome this challenge. Another approach involves manipulating the cell cycle — the process by which normal cells reproduce, grow, and eventually die.
In the latest advance in cellular engineering for this purpose, Jianyi Zhang, M.D., Ph.D., chair of the Department of Biomedical Engineering at the University of Alabama, Birmingham (UAB) and T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership, published an article in Circulation Research showing how to control key cell-cycle activators to improve the success rate of cardiomyocyte transplants. Dr. Zhang and his coauthors, using a mouse model of myocardial infarction, engineered the transplanted cells so that they expressed much higher levels of cyclin d2, a protein that plays a key role in cell division. Cardiac function improved significantly, and infarct size decreased in mice receiving these engineered the cells. The authors plan to test their discovery next in larger animal models.
Use of stem cells in tissue regeneration isn’t limited to the heart, of course. Stephanie Willerth, Ph.D., Canada Research Chair in Biomedical Engineering at the University of Victoria in Canada, is one of two recipients from that school of an Ignite Award from the British Columbia Innovation Council. Dr. Willerth will use her award to create “bioink” for three-dimensional printers. The bioink will convert skin cells into pluripotent stem cells using technology developed by Aspect Biosystems, a biotech company in Vancouver. Once induced, the pluripotent stem cells can be converted again into a number of different cell types. Dr. Willerth’s specific focus is building brain tissue with this technology.
Making Music
Prosthetic limbs have been a standard of care for amputees and people with underdeveloped arms or legs. Many current prostheses are designed to resemble actual limbs and use myoelectrical interfaces to re-create normal movements. Alternatively, other prostheses designed for specific purposes, such as the Flex-Foot Cheetah prosthetic foot for running, do not resemble the human limb but are optimized for a specific prosthetic function.
Now, a group of undergraduate bioengineering students at George Mason University (GMU) produced a prosthetic arm to play the violin. The students, who were instructed by Laurence Bray, Ph.D., associate chair of the Department of Bioengineering at GMU, were connected with a local fifth grader from nearby Alexandria, Va., named Isabella Nicola. Nicola was born without a left hand and only part of her left arm, and she had been learning violin using a prosthesis designed for her by her music teacher. The teacher, a GMU alumnus, reached out the department for help.
The design team used a three-dimensional printer to create a prosthetic arm for Isabella. The prosthesis is made of durable, lightweight plastic and includes a built-in bow, which Isabella can use to play her instrument. The prosthesis is hot pink — the color of Isabella’s choosing. She can now play the violin much more easily than before. Whether a symphony chair is in her future is up to her.
People and Places
The University of New Hampshire will use a five-year Center of Biomedical Research Excellence grant by the National Institutes of Health to create the Center of Integrated Biomedical and Bioengineering Research. The center will unite several colleges under the rubric of bioengineering and biomedical engineering. Similarly, the University of Iowa will use a $1.4 million grant from the Roy J. Carver Charitable Trust, an Iowa-based charity, to add a biomedical engineering laboratory for its College of Engineering.
Finally, congratulations to University of Minnesota Ph.D. BME student Lizzy Crist, who has been named the NCAA’s Woman of the Year, for her undergraduate record as a scholar-athlete (soccer) at Washington University in St. Louis. She joins last year’s winner, MIT biological engineering student Margaret Guo, a swimmer who is now an M.D./Ph.D. student at Stanford.
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.
