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November 8, 2017November 8, 2017

Penn Bioengineering at BMES 2017

BMES 2017

The annual meeting of the Biomedical Engineering Society (BMES) was held in Phoenix on October 11-14. The professional society for bioengineers and biomedical engineers this year played host not only to faculty from Penn’s Bioengineering Department but also to several undergraduate and graduate students, as well as staff

As previously mentioned here, three of the undergraduate students from the Center for Engineering MechanoBiology (CEMB) presented their work at the BMES meeting. The three students – Kimberly DeLuca from New Jersey Institute of Technology; John Durel from the University of Virginia; and Olivia Leavitt from Worcester Polytechnic Institute – spent 10 weeks over the summer at Penn working on individual research projects in the labs of Penn faculty.

Olivia worked in the laboratory of Beth Winkelstein, Ph.D., Professor of Bioengineering and Vice Provost for Education at Penn. Olivia’s project studied how matrix proteases influence the nerve impulses, but not the structure, of connective tissue. Jacob’s project, developed with Professor Jason Burdick, Ph.D., generated new insights into how single stem cells sense the mechanical environment and ‘make decisions’ about which type of cell they will become. Kimberly’s work was done in the lab of Robert Mauck, Ph.D., Professor of Orthopaedic Surgery at Penn’s Perelman School of Medicine, and it studies how to make materials with unique mechanical properties that could eventually find use in tissue engineering applications.

“I am very pleased to have been a part of the CEMB’s first round of undergraduate summer interns, and while there are certainly some small kinks to be worked out around the edges, the CEMB offered an invaluable experience. If I had to go back and decide again whether or not to chose this internship versus others, I would do it again in a heart-beat,” John Durel said.

BMES 2017 — (left to right) Bioengineering Department Chair David Meaney, BMES Co-president Olivia Teter, and GABE board members Meagan Ita and Varsha Viswanath.

Also attending BMES were officers of the undergraduate chapter of BMES at Penn. As we previously reported, the chapter won the Student Outreach Achievement Award for the year, repeating its win from 2015. Penn’s contingent from the BMES chapter, as well as from the Graduate Association of Bioengineers (GABE), were on hand to receive awards and recognition (see photo above).

Finally, Sevile Mannickarottu, instructional laboratories director for the Bioengineering Department, presented a paper at one of the conference sessions. Alongside presenters from MIT, Johns Hopkins, Berkeley, UCSD, UIUC, and Stanford, Sevile (see photo right) participated in a special sessions on curricular innovation held on Friday, October 13. Sevile did a great job explaining the innovations introduced to Penn’s undergraduate lab over the course of the last few years, and the presentation was very well received.

Next year’s BMES conference will be held in Atlanta on October 17-20, followed by the 2019 meeting in Philadelphia, to be co-chaired by Penn BE’s Jason Burdick.

October 30, 2017October 31, 2017

Week in BioE (October 30, 2017)

Using Stem Cells to Repair Damaged Tissue

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.

October 23, 2017October 20, 2017

Oncology/Engineering Review Published

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

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

October 20, 2017

Week in BioE (October 20, 2017)

Fetal Repair Without Surgery?

Spina bifida is a fairly common type of birth defect caused by incomplete closure of the backbone and tissue surrounding the spinal cord. Fetal surgery can repair the defect before delivery, but this invasive surgery can lead to high risk preterm delivery.

A new material may dramatically reduce the invasiveness of surgery needed to correct spina bifida. In a new article in Macromolecular Bioscience, surgeons and bioengineers from the University of Colorado report on one of these alternatives. One of the lead authors was Daewon Park, Ph.D., assistant professor of bioengineering. Dr. Park and his colleagues developed a reverse thermal gel, which is an injectable liquid that forms a gel at higher temperatures when injected into the body. Ultimately a gel like this one could be injected at or near the spine, where it would cover the defect in a spina bifida patient, harden into a gel, and ultimately repair the defect by deploying stem cells or engineered tissue.

The research team’s most recent study indicates that their gel retained its stability in amniotic fluid and was compatible with neural tube cells. They also tested the gel in two animal models, with successful results. The gel is still far from being used in actual fetal surgery cases, but the authors will continue to test the gel under conditions increasingly similar to the human amniotic sac.

Building Better Brains

UCLA scientists have developed an improved system for generating brain structures from stem cells. The team of scientists, led by Bennett G. Novitch, Ph.D., professor of neurobiology at UCLA, report their findings in Cell Reports. Importantly, the methods used by Dr. Novitch and his colleagues fine-tuned and simplified earlier efforts in this area, developing a method that did not require any specific reactors to generate the tissue. They were also able to generate tissue resembling the basal ganglia for the first time, indicating promise for using these tissues to model diseases affecting that part of the brain, including Parkinson’s disease.

Next, the authors demonstrated the usefulness of these “organoids” in modeling damage due to Zika virus. After exposing the generated organoids to Zika, the authors measured the cellular responses of the tissue, demonstrating the ability to use these tissues to model the disease. Given the recent epidemic of Zika virus in the Western Hemisphere, which focused attention on the virus’s effects on the human brain, in addition to microcephaly and other birth defects when the disease is transmitted from pregnant mothers to their children, understanding how Zika affects the developing brain is key to determining how to prevent the damage it causes and possibly repairing it. Reliable models of brain development are necessary, and the UCLA team’s findings seem to indicate that they’ve found one.

Rebuilding Brain Circuits After Injury

Among the issues in the prevention and treatment of head injury is that we still lack complete information about the mechanism underlying these injuries. However, a key piece of basic research recently published by a team at the University of North Carolina, Chapel Hill, demonstrates that a key aspect of this mechanism occurs in the axons, which are the stalks that grow from neurons to signal to each other. In an article published in Nature Communications, the team, led by Anne Marion Taylor, Ph.D., assistant professor of biomedical engineering at UNC, reports on using microfluidics technology to determine how neurons react when axons are severed. The authors found that damage to axons causes a compensatory loss of collateral connections to neighboring neurons. This loss in connectivity could be reversed by adding a protein, netrin-1, into the solution surrounding the neurons. Although netrin-1 was already known for its importance in rebuilding damaged axons, this work showed that netrin-1 has more widespread effects in rebuilding neural circuits after trauma.

Seeing Inside the Body

One of the key problems with minimally invasive surgical procedures is difficulty in shining sufficient light in the target region to see and manipulate tissue during surgery. Glass filaments are currently used, but they pose a health risk because they can break off in the body. A new citrate polymer fiber invented by scientists at Penn State University represents a much safer alternative to glass filaments. Reporting in Biomaterials, the scientists, led by Jian Yiang, Ph.D., associate professor of biomedical engineering at Penn State, describe how they developed the fiber and show how much less likely this polymer filament is to break when manipulated. If biocompatibility tests show that this polymer does not affect tissue health, it could eventually appear in surgical microscopes and make glass filaments a thing of the past.

Creating better illumination tools is one way of seeing inside the body. An elegant device developed by a team including MIT biomedical engineer Giovanni Traverso, Ph.D., consists of a proof-of-concept ingestable sensor that attaches to the stomach lining and can provide upper gastrointestinal system information for two days. The team reports on the device in a recent issue of Nature Biomedical Engineering. Unlike earlier ingestable diagnostic devices, the sensor developed by Dr. Traverso and his colleagues uses the contraction of the gut to power the device. It also surpassed pill-sized ingestable cameras by providing data from a longer time period.

Implants That Grow With Chilren

Using implants to treat medical problems in children is difficult for one simple reason: children can quickly outgrow their devices. The problem has been particularly acute among pediatric cardiac surgeons, for whom implants are commonly used devices. Now, thanks to collaboration between surgeons and a team including Jeffrey Karp, Ph.D., a Harvard biomedical engineer, valve implants that grow with patients could be here soon. Inspired by the clever design of a Chinese finger trap, the collaborators developed an implant that grows longer but thinner over time. They report on their device in Nature Biomedical Engineering, including its proof-of-principle testing in growing piglets. Based on these data, the study authors will continue to adapt and develop the device.

Say What?

Humans are especially good at listening to many voices at once or focusing on one voice in a crowded room. However, we really don’t know how we do this so well. Scientists at Imperial College London (ICL) solved part of this mystery. Reporting in eLife, the ICL authors developed a mathematical method to measure how the response to speech in a person’s brainstem changed when that person’s attention moved from one person to another. Perceptible changes in brainstem activity occurred when a person was intently listening to someone, and it disappeared when the person ignored speech. In addition to supplementing what we already know about how the brain stem participates in sensory tasks, the ICL team’s findings mean that damage to the brainstem – common to several neurological disorders – can easily affect how we process speech and interact with each other.

October 20, 2017

Lagrange Goes to Dani Bassett

Danielle S. Bassett, Eduardo D. Glandt Faculty Fellow and Associate Professor in the University of Pennsylvania’s Department of Bioengineering, is the recipient of the 2017 Lagrange-CRT Foundation Prize. The prize, given by the Institute for Scientific Interchange Foundation in Turin, Italy, was created to encourage and honor researchers working in the field of complex systems.

Complex systems feature many interconnected parts whose individual behavior influences the outcomes of the whole. Examples include social media networks, ecological webs, stock markets, and in Bassett’s case, the brain. Her research maps and analyzes the networks of neurons that enable all manners of cognitive abilities, as well as how those networks evolve during development or malfunction in disease.

The prize comes with an award of €50,000, or roughly $60,000. It will be formally presented to Bassett at a ceremony in Turin next week. Bassett is the first woman to be the sole recipient of the prize since its inception in 2008. Lada Adamic won it alongside Xavier Gabaix in 2012.

Read more at the SEAS blog on Medium.

October 18, 2017

Chairs for BMES ’19 to Include Burdick

chairs Jason Burdick, Ph.D., who is a professor in the University of Pennsylvania’s Department of Bioengineering, has been named one of the three chairs of the 2019 annual meeting of the Biomedical Engineering Society (BMES), which be held here in Philadelphia on October 16-19. Dr. Burdick will share this position with two other Philadelphians: Alisa Morss Clyne, Ph.D., an associate professor of mechanical engineering and mechanics at Drexel University; and Ruth Ochia, Ph.D., an associate professor of instruction in bioengineering at Temple University. Drs. Burdick, Clyne, and Ochia will share the responsibility for planning the meeting and chairing it once it is in session.

“I am very happy to be appointed as a program chair for the 2019 BMES meeting in Philadelphia, along with Alisa Morss Clyne of Drexel University and Ruth Ochia of Temple University,” Dr. Burdick said when asked about the honor. “The three of us felt that it was important to represent the various biomedical engineering research and education programs within the city of Philadelphia, since the meeting will be held here. There is such a wealth of biomedical engineering efforts in Philly that provides great opportunities to engage in outreach and interaction with both the community and local industry during the meeting.”

October 13, 2017

Week in BioE (October 13, 2017)

Seeing and Repairing Damaged Heart Vessels

Two common diagnostic procedures in cardiology are intravascular ultrasound and cardiac angiography. These procedures are performed to quantify the amount of plaque affecting a patient’s blood vessels. This information is vital because it helps to determine how advanced heart degree is, as well as guiding treatment planning and even the course of bypass surgery. However, the current technologies used for these procedures have significant limitations. Although conventional angiography can help to quantify the plaque burden, it does not offer any information about how much of the diameter of a vessel is blocked. Intravascular ultrasound is very good at quantifying plaque burden, but it is poor at identifying smaller features of compromised blood vessels.

One solution suggested to these issues is the combination of these imaging technologies into a single multimodal technique. Scientists led by Laura Marcu, Ph.D., professor of biomedical engineering at the University of California, Davis, invented a method combining intravascular ultrasound with multispectral fluorescence lifetime imaging (FLIM). As published in Scientific Reports, the device resembles a typical cardiac catheter but contains an optical fiber within the catheter that emits fluorescent light to characterize the plaque components before treatment.

Dr. Marcu and her colleagues tested their new device in live pigs and in human coronary arteries obtained from cadavers. The fluorescence data acquired with the device were comparable to those acquired with traditional fluorescence angiography. Moreover, the device could acquire data without having to administer a contrast agent, which can be dangerous in some patients due to allergies or weakened kidneys. The authors are currently seeking FDA approval to test their combined catheter in humans.

In addition to treating vessels before a heart attack can occur, there is new work showing how to efficiently repair heart tissue after a heart attack. A team of scientists collaborating among Clemson University, the Medical University of South Carolina, the University of South Carolina, and the University of Chicago has received a $1.5 million grant from the National Institutes of Health to examine a treatment that combines stem cells with nanowires. The principal investigator on the grant is Ying Mei, Ph.D., who is assistant professor of bioengineering at Clemson. Dr. Mei’s team mixes stem cells with nanowires so that they form spheroids that are larger than single cells and thus less likely to wash away. In addition, the investigators hope that the spheroids will mitigate the issue of the transplanted cells and the recipient’s heart beating at different rhythms. If successful, the group’s treatment paradigm could be a major step forward in stem cell therapies and cardiology.

Look, Up in the Sky!

Drones became famous when deployed on battlefields for the first time a decade ago. Since then, they’ve been adopted as a technology for a variety of purposes. For example, Amazon introduced delivery drones almost a year ago, and it has plans to expand its drone fleet enormously in coming years. It was only a matter of time before engineers began to imagine medical applications for drones.

Engineers in Australia and Iraq recently investigated whether a drone could be used to monitor cardiorespiratory signals remotely. They reported their findings in BioMedical Engineering OnLine. The authors used imaging photoplethysmography (PPG), which employs a video camera to detect visual indications on the skin of heart activity. They also applied advanced digital processing technology due to the tendency of PPG to be affected by sound and movement in the area of detection. By testing the combined technologies in 15 healthy volunteers, the authors found that their data compared well with several traditional techniques for monitoring vital signs. Among the possible applications that the authors imagine for this technology is battlefield triage performed remotely using drones. In the meantime, they will seek to fine-tune the technology’s abilities.

Concussion Distressingly Common

A research letter published in a recent issue of JAMA reports that a study conducted in Canada found that one in five adolescents sustained a concussion on at least one occasion. Of the approximately 20% of the study respondents who had experienced concussions, one quarter had suffered more than one. The letter is particularly relevant to the United States because of the similar popularity in Canada of contact and semicontact sports such as ice hockey and football. In addition, the study included more than 13,000 teenagers, lending significantly reliability to the conclusions.

Ending the Time of Cholera

Although largely eradicated in the developed world, cholera remains a major public health issue in the Global South and other parts of the developing world. The disease is a bacterial infection that causes severe gastrointestinal distress. Because the disease is transmitted via water, effective public sanitation is a core requirement of an effective prevention campaign.

One technology being deployed in this fight is a smartphone microfluidics platform that can determine the presence of the pathogen that causes cholera in a sample and report the data almost immediately to public health authorities. This technology was produced by a company called PathVis, which was spun off at Purdue University based on science produced the laboratories of Tamara Kinzer-Ursem, Ph.D., and Jacqueline Linnes, Ph.D., both of whom are assistant professors in Purdue’s Weldon School of Biomedical Engineering. There are plans to test PathVis in Haiti and to expand it to detect other diseases in the future.

The Latest on CRISPR

CRISPR/Cas9 is the biggest bioengineering story to come along in some time — certainly the biggest in genetic engineering. But the mere fact that it’s here and already being used in animals and in human cell lines doesn’t mean that the story is over. For instance, the Cas9 protein, which CRISPR deploys as part of its gene editing process, is currently developed most often using a viral vector. However, this system of delivery has certain drawbacks, not the least of which is a host immune system response when levels of the deployed viral vector reach the levels necessary for CRISPR to work.

A recent study published in Nature Biomedical Engineering reports on the successful use of gold nanoparticles to deliver Cas9. The new delivery system, called CRISPR-Gold, could obviate the need to use a viral vector as part of the CRISPR induction process. So far, the authors, led by University of California, Berkeley, bioengineers Irina Conboy, Ph.D., and Niren Murthy, Ph.D., have only used CRISPR-Gold in mice, but their successful results indicate that nonviral delivery with CRISPR is possible, so CRISPR could be used for more than previously thought.

October 2, 2017October 6, 2017

Week in BioE (October 6, 2017)

We Bleed Green

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

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

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

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

Breast Cancer News

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

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

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

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

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

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

A Review of Glucose Monitoring Technology

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

People and Places

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

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

September 29, 2017September 30, 2017

Week in BioE (September 29, 2017)

An Immune Cell Atlas

The human immune system deploys a variety of cells to counteract pathogens when they enter the body. B cells are a type of white blood cell specific to particular pathogens, and they form part of the adaptive immune system. As these cells develop, the cells with the strongest reactions to antigens are favored over others. This process is called clonal selection. Given the sheer number of pathogens out there, the number of different clonal lineages for B cells is estimated to be around 100 billion. A landscape like that can be difficult to navigate without a map.

Luckily, an atlas was recently published in Nature Biotechnology. It is the work of scientists collaborating between Penn’s own Perelman School of Medicine and faculty from the School of Biomedical Engineering, Science and Health Systems at our next-door neighbor, Drexel University. Using tissue samples from an organ donor network, the authors, led by Nina Luning Prak, MD, PhD, of Penn and Uri Heshberg, Ph.D., of Drexel, submitted the samples to a process called deep immune repertoire profiling to identify unique clones and clonal lineages. In total, they identified nearly a million lineages and mapped them to two networks: one in the gastointestinal tract and one that connects the blood, bone marrow, spleen, and lungs. This discovery suggests that the networks might be less complicated than initially thought. Also, it confirms a key role for the immune system in the gut.

Not only does this B cell atlas provide valuable information to the scientific community, but it also could serve as the basis for immune-based therapies for diseases. If we can identify these lineages and how clonal selection occurs, we could identify the most effective immunological cells and perhaps engineer them in the lab. At the very least, the extent to which scientists understand how B cells are formed and develop has received an enormous push with this research.

Understanding Muscle Movement

Natural movements of limbs require the coordinated activation of several muscle groups. Although the molecular composition of muscle is known, there remains a poor understanding of how these molecules coordinate their actions to confer power, strength, and endurance to muscle tissue. New fields of synthetic biology require this new knowledge to efficiently produce naturally inspired muscle substitutes.

Responding to this challenge, scientists at Carnegie Mellon University, including Philip R. LeDuc, Ph.D., William J. Brown Professor of Mechanical Engineering and Professor of Biomedical Engineering, have developed a computational system to better understand how mixtures of specific myosins affect muscle properties. Their method, published in PNAS, uses a computer model to show that mixtures of myosins will unexpectedly produce properties that are not the average of myosin molecular properties. Instead, the myosin mixtures coordinate and complement each other at the molecular level to create emergent behaviors, which lead to a robustness in how the muscle functions across a broad range. Dr. LeDuc and his colleagues then confirmed their model in lab experiments using muscle tissue from chickens. In the future, this new computational method could be used for other types of tissue, and it could prove useful in developing treatments for a variety of disorders.

Determining Brain Connectivity

How the brain forms and keeps memories is one of the greatest challenges in neuroscience. The hippocampus is a brain region considered critical for remembering sequences and events. The connections made by the hippocampus to other brain regions is considered critical for the hippocampus to integrate and remember experiences. However, this broad connectivity of the hippocampus to other brain areas raises a critical question: What connections are essential for rewiring the brain for new memories?

To offer an explanation for this question, a team of scientists in Hong Kong published a paper in PNAS in which they report on a study conducted in rats using resting-state function MRI. The study team, led by Ed X. Wu, Ph.D., of the University of Hong Kong, found that stimulation of a region deep in the hippocampus would propagate more broadly out into many areas of the cortex. The stimulation frequency affected how far this signal propagated from the hippocampus and pointed out the ability for frequency-based information signals to selectively connect the hippocampus to the rest of the brain. Altering the frequency of stimulation could affect visual function, indicating that targeted stimulation of the brain could have widespread functional effects throughout the brain.

Although human and rodent brains are obviously different, these findings from rats offer insights into how brain connectivity emerges in general. Similar studies in humans will be needed to corroborate these findings.

Seeing Inside a Tumor

Years of research have yielded the knowledge that the most effective treatments for cancer are often individualized. Knowing the genetic mutation involved in oncogenesis, for instance, can provide important information about the right drug to treat the tumor. Another important factor to know is the tumor’s chemical makeup, but far less is known about this factor due to the limitations of imaging.

However, a new study published in Nature Communications is offering some hope in this regard. In the study, scientists led by Xueding Wang, Ph.D., associate professor of biomedical engineering and radiology at the University of Michigan, used pH-sensing nanoprobes and multiwavelength photoacoustic imaging to determine tumor types in phantoms and animals. This new technology is based on the principle that cancerous cells frequently lower the pH levels in tissue, and designing probes with properties that are pH sensitive provides a method to find tumors with imaging methods and also treat these tumors.

With this technology, Dr. Wang and his colleagues were able to obtain three-dimensional images of pH levels inside of tumors. Importantly, it allowed them to noninvasively view the changes in a dye injected inside the tumor. Although a clinical application is years away, the information obtained using the Michigan team’s techniques could add significantly to our knowledge about tumorigenesis and tumor growth.

The Role of Bacteria in MS

The growing awareness of how bacteria interact with humans to affect health has led to the emergence of new scientific areas (e.g., human microbiome). Research findings from scientists collaborating between Caltech and UCSF suggest bacteria can play a role in the onset of multiple sclerosis. These investigators include Sarkis K. Mazmanian, Ph.D., Luis B. and Nelly Soux Professor of Microbiology and a faculty member in the Division of Biology and Biological Engineering at Caltech. Reporting their research results in PNAS, the researchers found several bacteria elevated in the MS microbiome. Study results showed that these bacteria regulated adaptive immune responses and helped to create a proinflammatory milieu. The identification of the bacteria interacting with immunity in MS patients could result in better diagnosis and treatment of this disabling disease.

People and Places

Faculty members at the University of California, Irvine, including biomedical engineer Zoran Nenadic, Ph.D., have received an $8 million grant to develop a brain-computer interface. The research using this grant aims to restore function in people with spinal cord injuries. Also, at the University of Texas, Austin, the lab of Amy Brock, Ph.D., an assistant professor in the Department of Biomedical Engineering, has received a three-year $180,000 R21 grant from the National Cancer Institute to develop a barcoding platform to isolate cancer cell lineages and to identify genetic targets for treatment.

September 19, 2017September 18, 2017

InnoWorks Academy Engages Local Teens

InnoWorks

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.

InnoWorks 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!”