Michael Mitchell Receives the 2022 SFB Young Investigator Award

by Ebonee Johnson

Michael Mitchell, Ph.D.

Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, has been awarded the 2022 Society for Biomaterials (SFB) Young Investigator Award for his “outstanding achievements in the field of biomaterials research.”

The Society for Biomaterials is a multidisciplinary society of academic, healthcare, governmental and business professionals dedicated to promoting advancements in all aspects of biomaterial science, education and professional standards to enhance human health and quality of life.

Mitchell, whose research lies at the interface of biomaterials science, drug delivery, and cellular and molecular bioengineering to fundamentally understand and therapeutically target biological barriers, is specifically being recognized for his development of the first nanoparticle RNAi therapy to treat multiple myeloma, an incurable hematologic cancer that colonizes in bone marrow.

“Before this, no one in the drug delivery field has developed an effective gene delivery system to target bone marrow,” said United States National Medal of Science recipient Robert S. Langer in Mitchell’s award citation. “Mike is a standout young investigator and leader that intimately understands the importance of research and collaboration at the interface of nanotechnology and medicine.”

Academic recipients of the SFB Young Investigator Award should not exceed the rank of Assistant Professor and must not be tenured at the time of nomination. The award includes a $1,000 endowment.

This story originally appeared in Penn Engineering Today.

Yogesh Goyal Appointed Assistant Professor at Northwestern University

Yogesh Goyal, Ph.D.

The Department of Bioengineering is proud to congratulate Yogesh Goyal on his appointment as Assistant Professor in the Department of Cell and Developmental Biology (CDB) in the Feinberg School of Medicine at Northwestern University. His lab will be housed within the Center for Synthetic Biology. His appointment will begin in Spring 2022.

Yogesh grew up in Chopra Bazar, a small rural settlement in Jammu and Kashmir, India. He received his undergraduate degree in Chemical Engineering from the Indian Institute of Technology Gandhinagar. Yogesh joined Princeton University for his Ph.D. in Chemical and Biological Engineering, jointly mentored by Professors Stanislav Shvartsman and Gertrud Schüpbach. Yogesh is currently a Jane Coffin Childs Postdoctoral Fellow in the lab of Arjun Raj, Professor in Bioengineering and Genetics at Penn.

“I am so excited for Yogesh beginning his faculty career,” Raj says. “He is a wonderful scientist with a sense of aesthetics. His work is simultaneously significant and elegant, a powerful combination.”

With a unique background in engineering, developmental biology, biophysical modeling, and single-cell biology, Yogesh develops quantitative approaches to problems in developmental biology and cancer drug resistance. As a postdoc, Yogesh developed theoretical and experimental lineage tracing approaches to study how non-genetic fluctuations may arise within genetically identical cancer cells and how these fluctuations affect the outcomes upon exposure to targeted therapy drugs. The Goyal Lab at Northwestern will “combine novel experimental, computational, and theoretical frameworks to monitor, perturb, model, and ultimately control single-cell variabilities and emergent fate choices in development and disease, including cancer and developmental disorders.”

“I am excited to start a new chapter in my academic career at Northwestern University,” Goyal says. “I am grateful for my time at Penn Bioengineering, and I thank my mentor Arjun Raj and the rest of the lab members for making this time intellectually and personally stimulating.”

Congratulations to Dr. Goyal from everyone at Penn Bioengineering!

BE Seminar: “Understanding Spatiotemporal Cell Reprogramming for Precision Medicine” (Xiling Shen)

Xiling Shen, Ph.D.

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.

BE Seminar: “High-throughput Screening of a Combinatorial CAR Co-stimulatory Domain Library” (Kyle Daniels)

Kyle Daniels, PhD

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.

Week in BioE (June 28, 2019)

by Sophie Burkholder

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.

Read the rest of this story on Penn Today.

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.

 

Penn Engineers: Cells Require Gene Expression Feedback to Keep Moving

By Lauren Salig

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.

The study was published in the Journal of Cell Biology.

Read the full story at the Penn Engineering Medium Blog.

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.

 

Week in BioE (February 27, 2018)

Pain Relief Using Spearmint Aromatherapy

spearmintPain 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 Engineering details 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.

Week in BioE (February 2, 2018)

Broccoli + Yogurt = Cancer Prevention?

broccoliGeorge 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.

Week in BioE (December 15, 2017)

A New Model of the Small Intestine

small intestine
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!