Jennifer Phillips-Cremins Promoted to Associate Professor

 

Jennifer Phillips-Cremins, Ph.D.

by Sophie Burkholder

Jennifer Phillips-Cremins, Ph.D., was recently promoted to the tenured position of Associate Professor in Penn’s Department of Bioengineering. Cremins, leads a lab on campus in 3D Epigenomes and Systems Neurobiology.

In a recent piece profiling top technologies to watch in 2020, Cremins spoke to Nature about which technological trends she saw as being important for the year to come. In the panel, which highlighted perspectives from a panel of researchers across several fields, Cremins discussed the increasing relevance of innovations that would allow researchers to study the way that folding patterns within the human genome can influence how genes are expressed in  healthy individuals and misregulated in human disease.

One such innovation is actually employed by the Cremins Lab: light-activated dynamic looping (LADL). This technique uses both CRISPR/Cas9 and optogenetics to induce folding patterns into the genome on demand, using light as a trigger. In doing so, Cremins and her fellow researchers can more efficiently study the patterns of the human genome, and what effects certain folding patterns can have on the gene expression  state of the cell.

Now, with her new promotion, Cremins can continue advancing her research in understanding the genetic and epigenetic mechanisms that regulate neural connections during brain development, with a focus on how that understanding can eventually lead to better treatments of neurological disease. Beyond the lab, she’ll now lead a new Spatial Epigenetics program, bringing together scientists across Penn’s campus to understand how the spatial connections between biomolecules influence biological behavior. She will also continue teaching her hallmark course for Penn Bioengineering undergraduate students, Biological Data Science, and her more advanced graduate-level course in epigenomics. Congratulations, Dr. Cremins!

The Optimal Immune Repertoire for Bacteria

by Erica K. Brockmeier

Transmission electron micrograph of multiple bacteriophages, viruses that infect bacteria, attached to a cell wall. New research describes how bacteria can optimize their “memory” of past viral infections in order to launch an effective immune response against a new invader. (Image: Graham Beards)

Before CRISPR became a household name as a tool for gene editing, researchers had been studying this unique family of DNA sequences and its role in the bacterial immune response to viruses. The region of the bacterial genome known as the CRISPR cassette contains pieces of viral genomes, a genomic “memory” of previous infections. But what was surprising to researchers is that rather than storing remnants of every single virus encountered, bacteria only keep a small portion of what they could hold within their relatively large genomes.

Work published in the Proceedings of the National Academy of Sciences provides a new physical model that explains this phenomenon as a tradeoff between how much memory bacteria can keep versus how efficiently they can respond to new viral infections. Conducted by researchers at the American Physical Society, Max Planck Institute, University of Pennsylvania, and University of Toronto, the model found an optimal size for a bacteria’s immune repertoire and provides fundamental theoretical insights into how CRISPR works.

In recent years, CRISPR has become the go-to biotechnology platform, with the potential to transform medicine and bioengineering. In bacteria, CRISPR is a heritable and adaptive immune system that allows cells to fight viral infections: As bacteria come into contact with viruses, they acquire chunks of viral DNA called spacers that are incorporated into the bacteria’s genome. When the bacteria are attacked by a new virus, spacers are copied from the genome and linked onto molecular machines known as Cas proteins. If the attached sequence matches that of the viral invader, the Cas proteins will destroy the virus.

Bacteria have a different type of immune system than vertebrates, explains senior author Vijay Balasubramanian, but studying bacteria is an opportunity for researchers to learn more about the fundamentals of adaptive immunity. “Bacteria are simpler, so if you want to understand the logic of immune systems, the way to do that would be in bacteria,” he says. “We may be able to understand the statistical principles of effective immunity within the broader question of how to organize an immune system.”

Read more on Penn Today.

Vijay Balasubramanian is the Cathy and Marc Lasry Professor in the Department of Physics and Astronomy in the School of Arts & Sciences at the University of Pennsylvania and a member of the Department of Bioengineering Graduate Group

This research was supported by the Simons Foundation (Grant 400425) and National Science Foundation Center for the Physics of Biological Function (Grant PHY-1734030). 

Daniel A. Hammer and Miriam Wattenbarger to Offer Summer Course on COVID-19

Daniel A. Hammer and Miriam Wattenbarger

As researchers hunt for a solution to the coronavirus outbreak, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and in Chemical and Biomolecular Engineering (CBE), is bringing lessons from the fight for a vaccine to the classroom.

Hammer will offer a course on COVID-19 and the coronavirus pandemic during Penn’s Summer II session, which will be held online this year. The course will be co-taught with Miriam Wattenbarger, senior lecturer in CBE.

The course, “Biotechnology, Immunology, and COVID-19,” will culminate with a case study of the coronavirus pandemic including the types of drugs proposed and their mechanism of action, as well as the process of vaccine development.

“Obviously, the pandemic has been a life-altering event, causing an immense dislocation for everyone in our community, especially the students. Between me and Miriam, who has been trumpeting the importance of vaccines for some time in her graduate-level CBE courses, we have the expertise to inform students about this disease and how we might combat it,” says Hammer.

For more than ten years, Wattenbarger has run courses and labs focused on drug delivery and biotechnology, key elements of the vaccine development process.

“I invite both researchers and industry speakers to meet with my students,” Wattenbarger says, “so that they learn the crucial role engineers play in both vaccine development and manufacturing.”

Beyond studying the interactions between the immune system and viruses — including HIV, influenza, adenovirus and coronavirus — students will cover a variety of biotechnological techniques relevant to tracking and defending against them, including recombinant DNA technology, polymerase chain reaction, DNA sequencing, gene therapy, CRISPR-Cas9 editing, drug discovery, small molecule inhibitors, vaccines and the clinical trial process.

Students will also learn the mathematical principles used to quantify biomolecular interactions, as well as those found behind simple epidemiological models and methods for making and purifying drugs and vaccines.

“We all have to contribute in the ways that we can. Having taught biotechnology to freshmen for the past decade, this is something that I can do that can both inform and build community,” says Hammer. “Never has it been more important to have an informed and scientifically literate community that can fight this or any future pandemic.”

Originally posted on the Penn Engineering blog. Media contact Evan Lerner. For more on BE’s COVID-19 projects, read our recent blog post.

Jennifer Phillips-Cremins Featured in Nature’s ‘Technologies to Watch in 2020’

Jennifer Phillips-Cremins, Ph.D.

Nature, one of the world’s most prestigious scientific journals, recently reached out to a panel of researchers from a variety of fields, asking them what technological trends they see as having the most impact on their disciplines in the coming year.

Jennifer Phillips-Cremins, assistant professor in the Department of Bioengineering, was among these panelists. As an expert in “3D epigenetics,” or the way the genome’s highly specific folding patterns influence how and when individual genes are expressed, she highlighted a slate of new techniques that will allow researchers to take a closer look at those relationships.

Read the full post at Penn Engineering blog. Media contact Evan Lerner.

Bioengineering Round-Up (December 2019)

by Sophie Burkholder

Positive results in first-in-U.S. trial of CRISPR-edited immune cells

3D render of the CRISPR-Cas9 genome editing system

Genetically editing a cancer patient’s immune cells using CRISPR/Cas9 technology, then infusing those cells back into the patient appears safe and feasible based on early data from the first-ever clinical trial to test the approach in humans in the United States. Researchers from the Abramson Cancer Center have infused three participants in the trial thus far—two with multiple myeloma and one with sarcoma—and have observed the edited T cells expand and bind to their tumor target with no serious side effects related to the investigational approach. Penn is conducting the ongoing study in cooperation with the Parker Institute for Cancer Immunotherapy and Tmunity Therapeutics.

“This trial is primarily concerned with three questions: Can we edit T cells in this specific way? Are the resulting T cells functional? And are these cells safe to infuse into a patient? This early data suggests that the answer to all three questions may be yes,” says the study’s principal investigator Edward A. Stadtmauer, section chief of Hematologic Malignancies at Penn. Stadtmauer will present the findings next month at the 61st American Society of Hematology Annual Meeting and Exposition.

Read the rest of the story on Penn Today.

Tulane researchers join NIH HEAL initiative for research into opioid crisis

A Tulane University professor and researcher of biomedical engineering will join fellow researchers from over 40 other institutions in the National Institute of Health’s Help to End Addiction Long-Term (HEAL) Initiative. Of the $945 million that make up the project, Michael J. Moore, Ph.D. will receive a share of $1.2 million to advance research in modeling human pain through computer chips, with the help of fellow Tulane researchers Jeffrey Tasker, Ph.D., and James Zadina, Ph.D., each with backgrounds in neuroscience.

Because of the opioid epidemic sweeping the nation, Moore notes that there’s a rapid search going on to develop non-addictive painkiller options. However, he also sees a gap in adequate models to test those new drugs before human clinical trials are allowed to take place. Here is where he hopes to step in and bring some innovation to the field, by integrating living human cells into a computer chip for modeling pain mechanisms. Through his research, Moore wants to better understand not only how some drugs can induce pain, but also how patients can grow tolerant to some drugs over time. If successful, Moore’s work will lead to a more rapid and less expensive screening option for experimental drug advancements.

New machine learning-assisted microscope yields improved diagnostics

Researchers at Duke University recently developed a microscope that uses machine learning to adapt its lighting angles, colors, and patterns for diagnostic tests as needed. Most microscopes have lighting tailored to human vision, with an equal distribution of light that’s optimized for human eyes. But by prioritizing the computer’s vision in this new microscope, researchers enable it to see aspects of samples that humans simply can’t, allowing for a more accurate and efficient diagnostic approach.

Led by Roarke W. Horstmeyer, Ph.D., the computer-assisted microscope will diffuse light through a bowl-shaped source, allowing for a much wider range of illumination angles than traditional microscopes. With the help of convolutional neural networks — a special kind of machine learning algorithm — Horstmeyer and his team were able to tailor the microscope to accurately diagnose malaria in red blood cell samples. Where human physicians typically perform similar diagnostics with a rate of 75 percent accuracy, this new microscope can do the same work with 90 percent accuracy, making the diagnostic process for many diseases much more efficient.

Case Western Reserve University researchers create first-ever holographic map of brain

A Case Western Reserve University team of researchers recently spearheaded a project in creating an interactive holographic mapping system of the human brain. The design, which is believed to be the first of its kind, involves the use of the Microsoft HoloLens mixed reality platform. Lead researcher Cameron McIntyre, Ph.D., sees this mapping system as a better way of creating holographic navigational routes for deep brain stimulation. Recent beta tests with the map by clinicians give McIntyre hope that the holographic representation will help them better understand some of the uncertainties behind targeted brain surgeries.

More than merely providing a useful tool, McIntyre’s project also brings together decades’ worth of neurological data that has not yet been seriously studied together in one system. The three-dimensional atlas, called “HoloDBS” by his lab, provides a way of finally seeing the way all of existing neuro-anatomical data relates to each other, allowing clinicians who use the tool to better understand the brain on both an analytical and visual basis.

Implantable cancer traps reduce biopsy incidence and improve diagnostic

Biopsies are one of the most common procedures used for cancer diagnostics, involving a painful and invasive surgery. Researchers at the University of Michigan are trying to change that. Lonnie Shea, Ph.D., a professor of biomedical engineering at the university, worked with his lab to develop implants with the ability to attract any cancer cells within the body. The implant can be inserted through a scaffold placed under the patient’s skin, making it a more ideal option than biopsy for inaccessible organs like lungs.

The lab’s latest work on the project, published in Cancer Research, details its ability to capture metastatic breast cancer cells in vivo. Instead of needing to take biopsies from areas deeper within the body, the implant allows for a much simpler surgical procedure, as biopsies can be taken from the implant itself. Beyond its initial diagnostic advantages, the implant also has the ability to attract immune cells with tumor cells. By studying both types of cells, the implant can give information about the current state of cancer in a patient’s body and about how it might progress. Finally, by attracting tumor and immune cells, the implant has the ability to draw them away from the area of concern, acting in some ways as a treatment for cancer itself.

People and Places

Cesar de la Fuente-Nunez, PhD

The Philadelphia Inquirer recently published an article detailing the research of Penn’s Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, Cesar de la Fuente, Ph.D. In response to a growing level of worldwide deaths due to antibiotic-resistant bacteria, de la Fuente and his lab use synthetic biology, computation, and artificial intelligence to test hundreds of millions of variations in bacteria-killing proteins in the same experiment. Through his research, de la Fuente opens the door to new ways of finding and testing future antibiotics that might be the only viable options in a world with an increasing level of drug-resistant bacteria

Emily Eastburn, a Ph.D. candidate in Bioengineering at Penn and a member of the Boerckel lab of the McKay Orthopaedic Research Laboratory, recently won the Ashton fellowship. The Ashton fellowship is an award for postdoctoral students in any field of engineering that are under the age of 25, third-generation American citizens, and residents of either Pennsylvania or New Jersey. A new member of the Boerckel lab, having joined earlier this fall, Eastburn will have the opportunity to conduct research throughout her Ph.D. program in the developmental mechanobiology and regeneration that the Boerckel lab focuses on.

Cesar de la Fuente ‘Trends in Immunology’ Literature Review

by Sophie Burkholder

 

Cesar de la Fuente, PhD

Cesar de la Fuente, Ph.D., a Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering at Penn, recently published a literature review in Trends in Immunology entitled, “Emerging Frontiers in Microbiome Engineering.” The microbiome, in simple terms, consists of the genetic material of microorganisms in the gut, including bacteria, fungi, protozoa,  viruses, and oral, vaginal, and skin microbiomes. Each human has a unique microbiome that depends both on predetermined factors like exposure to microorganisms within a mother’s birth canal or breastmilk in early life as well as environmental factors and diet in later life. The health of someone’s microbiome is extremely important, as an unhealthy microbiome with an imbalance of symbiotic and pathogenic microbes can make a person more susceptible to various diseases. The most common diseases or disorders associated with a problematic microbiome are rather far-reaching, including some of the most afflicting diseases of today like inflammatory bowel disease, diabetes, obesity, cardiovascular diseases, and neurological disorders.

In his recent literature review, de la Fuente provides an overview of microbiome engineering, and what the future might hold for the field. He defines microbiome engineering initially as a way of studying the “contribution of individual microbes and generating potential therapies against metabolic, inflammatory, and immunological diseases.” Currently, most treatments for issues with the microbiome are broad solutions like dietary adjustments to include more probiotics, antibiotics, or prebiotics, while more serious cases may require a fecal microbiota transplant. While these therapies may work for some patients, de la Fuente emphasizes the need for greater specificity in treatment targets and a need for precision in reprogramming existing microbial communities as an alternative to transplants.

De la Fuente highlights the current methods and tools in microbiome engineering such as the use of bacteriocins and bacteriophages to knock out specific bacteria within the microbiome. However, there are very few bacteriocins or bacteriophages commercially available on today’s market. Another common approach to microbiome engineering is in synthetic biology, or the use of “chassis” — a type of cell that maintains DNA constructs for different functions — to engineering interactions within the microbiome. De la Fuente continues his discussion of current methods by naming and describing several specific examples of these approaches, particularly in relation to synthetic biology options before moving on to examine future directions for these methods.

Before bringing up potential new frontiers for microbiome engineering, de la Fuente also outlines the way that microbiome engineering works in the first place, and dedicates sections of the review to the microbiome’s influence on its host’s immune system and how to engineer the microbiome to modulate that immune system. The main future methods for microbiome engineering that de la Fuente points out in his review include more precise regulation of gene expression through commensal organisms and the use of CRISPRi to find genes involved in bacterial maintenance. The conclusion of de la Fuente’s review brings up the notion of new personalized medicine or therapy for the microbiome that could come with further advances in the field. However, he also makes sure to bring up some still-outstanding questions about the human microbiome that require further research, most notably, what exactly makes a healthy human microbiome? Here’s hoping the research de la Fuente mentions can illuminate a path to the answer.

Penn Engineers’ ‘LADL’ Uses Light to Serve Up On-demand Genome Folding

Every cell in your body has a copy of your genome, tightly coiled and packed into its nucleus. Since every copy is effectively identical, the difference between cell types and their biological functions comes down to which, how and when the individual genes in the genome are expressed, or translated into proteins.

Scientists are increasingly understanding the role that genome folding plays in this process. The way in which that linear sequence of genes are packed into the nucleus determines which genes come into physical contact with each other, which in turn influences gene expression.

LADL combines CRISPR/Cas9 and optogenetics to bring two distant points in a linear gene sequence into physical contact, forming a folding pattern known as a “loop.” Looping interactions influence gene expression, so the researchers envision LADL as being a powerful tool for studying these dynamics.

Jennifer Phillips-Cremins, assistant professor in Penn Engineering’s Department of Bioengineering, is a pioneer in this field, known as “3-D Epigenetics.” She and her colleagues have now demonstrated a new technique for quickly creating specific folding patterns on demand, using light as a trigger.

The technique, known as LADL or light-activated dynamic looping, combines aspects of two other powerful biotechnological tools: CRISPR/Cas9 and optogenetics. By using the former to target the ends of a specific genome fold, or loop, and then using the latter to snap the ends together like a magnet, the researchers can temporarily create loops between exact genomic segments in a matter of hours.

The ability to make these genome folds, and undo them, on such a short timeframe makes LADL a promising tool for studying 3D-epigenetic mechanisms in more detail. With previous research from the Phillips-Cremins lab implicating these mechanisms in a variety of neurodevelopmental diseases, they hope LADL will eventually play a role in future studies, or even treatments.

Jennifer Phillips-Cremins, Ji Hun Kim and Mayuri Rege

Alongside Phillips-Cremins, lab members Ji Hun Kim and Mayuri Rege led the study, and Jacqueline Valeri, Aryeh Metzger, Katelyn R. Titus, Thomas G. Gilgenast, Wanfeng Gong and Jonathan A. Beagan contributed to it. They collaborated with associate professor of Bioengineering Arjun Raj and Margaret C. Dunagin, a member of his lab.

The study was published in the journal Nature Methods.

“In recent years,” Phillips-Cremins says, “scientists in our fields have overcome technical and experimental challenges in order to create ultra-high resolution maps of how the DNA folds into intricate 3D patterns within the nucleus. Although we are now capable of visualizing the topological structures, such as loops, there is a critical gap in knowledge in how genome structure configurations contribute to genome function.”

In order to conduct experiments on these relationships, researchers studying these 3D patterns were in need of tools that could manipulate specific loops on command. Beyond the intrinsic physical challenges — putting two distant parts of the linear genome in physical contact is quite literally like threading a needle with a thread that is only a few atoms thick — such a technique would need to be rapid, reversible and work on the target regions with a minimum of disturbance to neighboring sequences.

The advent of CRISPR/Cas9 solved the targeting problem. A modification of the gene editing tool allowed researchers to home in on the desired sequences of DNA on either end of the loop they wanted to form. If those sequences could be engineered to seek one another out and snap together under the other necessary conditions, the loop could be formed on demand.

Cremins Lab members then sought out biological mechanisms that could bind the ends of the loops together, and found an ideal one in the toolkit of optogenetics. The proteins CIB1 and CRY2, found in Arabidopsis, a flowering plant that’s a common model organism for geneticists, are known to bind together when exposed to blue light.

“Once we turn the light on, these mechanisms begin working in a matter of milliseconds and make loops within four hours,” says Rege. “And when we turn the light off, the proteins disassociate, meaning that we expect the loop to fall apart.”

“There are tens of thousands of DNA loops formed in a cell,” Kim says. “Some are formed slowly, but many are fast, occurring within the span of a second. If we want to study those faster looping mechanisms, we need tools that can act on a comparable time scales.”

As shown in a 2013 Nature Methods paper by fellow Penn bioengineer Lukasz Bugaj, the optical response of the CRY2 protein is a key component of LADL. When the blue light is turned on, CRY2 proteins in cell immediately find one another and bind together into clumps large enough to be seen under magnification. When the light is turned off, the clumps begin to dissolve away.”

Fast acting folding mechanisms also have an advantage in that they lead to fewer perturbations of the surrounding genome, reducing the potential for unintended effects that would add noise to an experiment’s results.

The researchers tested LADL’s ability to create the desired loops using their high-definition 3D genome mapping techniques. With the help of Arjun Raj, an expert in measuring the activity of transcriptional RNA sequences, they also were able to demonstrate that the newly created loops were impacting gene expression.

The promise of the field of 3D-epigenetics is in investigating the relationships between these long-range loops and mechanisms that determine the timing and quantity of the proteins they code for. Being able to engineer those loops means researchers will be able to mimic those mechanisms in experimental conditions, making LADL a critical tool for studying the role of genome folding on a variety of diseases and disorders.

“It is critical to understand the genome structure-function relationship on short timescales because the spatiotemporal regulation of gene expression is essential to faithful human development and because the mis-expression of genes often goes wrong in human disease,” Phillips-Cremins says. “The engineering of genome topology with light opens up new possibilities to understanding the cause-and-effect of this relationship. Moreover we anticipate that, over the long term, the use of light will allow us to target specific human tissues and even to control looping in specific neuron subtypes in the brain.”

The research was supported by the New York Stem Cell Foundation; Alfred P. Sloan Foundation; the National Institutes of Health through its Director’s New Innovator Award from the National Institute of Mental Health, grant no. 1DP2MH11024701, and a 4D Nucleome Common Fund, grant no. 1U01HL1299980; and the National Science Foundation through a joint NSF-National Institute of General Medical Sciences grant to support research at the interface of the biological and mathematical sciences, grant no. 1562665, and a Graduate Research Fellowship, grant no. DGE-1321851.

Originally published on the Penn Engineering Medium blog.

Week in BioE: April 5, 2019

by Sophie Burkholder

Tulane Researchers Use Cancer Imaging Technique to Help Detect Preeclampsia

Preeclampsia is potentially life-threatening pregnancy disorder that typically occurs in about 200,000 expectant mothers every year. With symptoms of high blood pressure, swelling of the hands and feet, and protein presence in urine, preeclampsia is usually treatable if diagnosed early enough. However, current methods for diagnosis involve invasive procedures like cordocentesis, a procedure which takes a sample of fetal blood.

Researchers at Tulane School of Medicine led by assistant professor of bioengineering Carolyn Bayer, Ph.D., hope to improve diagnostics for preeclampsia with the use of spectral photoacoustic imaging. Using this technique, Bayer’s team noticed a nearly 12 percent decrease in placental oxygenation in rats with induced preeclampsia when compared to normal pregnant rats after only two days. If success in using this imaging technology continues at the clinical level, Bayer plans to find more applications of it in the detection and diagnosis of breast and ovarian cancers as well.

New CRISPR-powered device detects genetic mutations in minutes 

Two groups of researchers from the University of California, Berkeley and the Keck Graduate Institute of the Claremont Colleges recently collaborated to design what they call a “CRISPR-Chip” –  a combination of the CRISPR-Cas9 System with a graphene transistor to sequence DNA for the purpose of genetic mutation diagnosis. While companies like 23andMe made genetic testing and analysis more common and accessible for the general public in recent years, the CRISPR-Chip looks to streamline the technology even more.

This new chip eliminates the long and expensive amplification process involved in the typical polymerase chain reaction (PCR) used to read DNA sequences. In doing so, the CRISPR-Chip is much more of a point-of-care diagnostic, having the ability to quickly detect a given mutation or sequence when given a pure DNA sample. Led by Kiana Aran, Ph.D., the research team behind the CRISPR-Chip hopes that this new combination of nanoelectronics and modern biology will allow for a new world of possibilities in personalized medicine.

New Method of Brain Stimulation Might Alleviate Symptoms of Depression

Depression is one of the most common mental health disorders in the United States, with nearly 3 million cases every year. For most patients suffering from depression, treatment involves prolonged psychotherapy, antidepressant medication, or even electroconvulsive therapy in extreme cases. Now, scientists at the University of North Carolina School of Medicine study the use of transcranial alternating current stimulation (tACS) to alleviate symptoms of depression.

Led by Flavio Frohlich, Ph.D., who has an adjunct appointment in biomedical engineering, this team of researchers based this new solution on information from each patient’s specific alpha oscillations, which are a kind of wave that can be detected by an electroencephalogram (EEG). Those who suffer from depression tend to have imbalanced alpha oscillations, so Frohlich and his team sought to use tACS to restore this balance in those patients. After seeing positive results from data collected two weeks after patients in a clinical trial receives the tACS treatment, Frohlich hopes that future applications will include treatment for even more mental health disorders and psychiatric illnesses.

University of Utah Researchers Receive Grant to Improve Hearing Devices for Deaf Patients

Engineers at the University of Utah are part of team that recently received a $9.7 million grant from the National Institute of Health (NIH) to design new implantable hearing devices for deaf patients, with the hope to improve beyond the sound quality of existing devices. The work will build upon a previous project at the University of Utah called the Utah Electrode Array, a brain-computer interface originally developed by Richard Normann, Ph.D., that can send and receive neural impulses to and from the brain. This new device will differ from a typical cochlear implant because the Utah Electrode Array assembly will be attached directly to the auditory nerve instead of the cochlea, providing the patient with a much higher resolution of sound.

People & Places

Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Scholar in the Department of Materials Science and Engineering and Secondary Faculty in Bioengineering, has been named the recipient of the 2018–19 George H. Heilmeier Faculty Award for Excellence in Research for “for pioneering multi-scale models of nanomaterials and biological systems.”

The Heilmeier Award honors a Penn Engineering faculty member whose work is scientifically meritorious and has high technological impact and visibility. It is named for George H. Heilmeier, a Penn Engineering alumnus and overseer whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize.

Read the rest of the story on Penn Engineering’s Medium blog.

We would also like to congratulate Jay Goldberg, Ph.D., from Marquette University on his election as a fellow to the National Academy of Inventors. Nominated largely for his six patents involving medical devices, Goldberg also brings this innovation to his courses. One in particular called Clinical Issues in Biomedical Engineering Design allows junior and senior undergraduates to observe the use of technology in clinical settings like the operating room, in an effort to get students thinking about how to improve the use of medical devices in these areas.

 

Week in BioE (March 22, 2019)

by Sophie Burkholder

A New Microscopy Technique Could Reduce the Risk of LASIK Surgery

Though over ten million Americans have undergone LASIK vision corrective surgery since the option became available about 20 years ago, the procedure still poses some risk to patients. In addition to the usual risks of any surgery however, LASIK has even more due to the lack of a precise way to measure the refractive properties of the eye, which forces surgeons to make approximations in their measurements during the procedure. In an effort to eliminate this risk, a University of Maryland team of researchers in the Optics Biotech Laboratory led by Giuliano Scarcelli, Ph. D., designed a microscopy technique that would allow for precise measurements of these properties.

Using a form of light-scattering technology called Brillouin spectroscopy, Scarcelli and his lab found a way to directly determine a patient’s refractive index – the quantity surgeons need to know to be able to measure and adjust the way light travels through the eye. Often used as a way to sense mechanical properties of tissues and cells, this technology holds promise for taking three-dimensional spatial observations of these structures around the eye. Scarcelli hopes to keep improving the resolution of the new technique, to further understanding of the eye, and reduce even more of the risks involved with LASIK surgery.

Taking Tissue Models to the Final Frontier

Space flight is likely to cause deleterious changes to the composition of bacterial flora, leading to an increased risk of infection. The environment may also affect the susceptibility of microorganisms within the spacecraft to antibiotics, key components of flown medical kits, and may modify the virulence of bacteria and other microorganisms that contaminate the fabric of the International Space Station and other flight platforms.

“It has been known since the early days of human space flight that astronauts are more prone to infection,” says Dongeun (Dan) Huh, Wilf Family Term Assistant Professor in Bioengineering at Penn Engineering. “Infections can potentially be a serious threat to astronauts, but we don’t have a good fundamental understanding of how the microgravity environment changes the way our immune system reacts to pathogens.”

In collaboration with G. Scott Worthen, a physician-scientist in neonatology at the Children’s Hospital of Philadelphia, Huh will attempt to answer this question by sending tissues-on-chips to space. Last June, the Center for the Advancement of Science in Space (CASIS) and the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH), announced that the duo had received funding to study lung host defense in microgravity at the International Space Station.

Huh and Worthen aim to model respiratory infection, which accounts for more than 30 percent of all infections reported in astronauts. The project’s goals are to test engineered systems that model the airway and bone marrow, a critical organ in the immune system responsible for generating white blood cells, and to combine the models to emulate and understand the integrated immune responses of the human respiratory system in microgravity.

Read the rest of the article on Penn Engineering’s Medium Blog. Media contacts Evan Lerner and Janelle Weaver.

Sappi Limited Teams Up with the University of Maine to Develop Paper Microfluidics

At the Westbrook Technology Center of Sappi, a global pulp and paper company, researchers found ways to apply innovations in paper texture for medical use. So far, these include endeavors in medical test devices and patches for patient diagnostics. In collaboration with the Caitlin Howell, Ph.D., Assistant Professor of Chemical and Biomedical Engineering at the University of Maine, Sappi hopes to continue advances in these unconventional uses of their paper, especially as the business in paper for publishing purposes declines.

Sappi’s projects with the university focus on the development of paper microfluidics devices as what’s now becoming a widespread solution for obstacles in point-of-care diagnostics. One project in particular, called Sharklet, uses a paper that mimics shark skin as a way to impede unwanted microbial growth on the device – a key characteristic needed for its transition into commercial use. Beyond this example, Sappi’s work in developing paper microfluidics underscores the benefits of these devices in their mass producibility and adaptability.

New Observations of the WNT Pathway Deepen the Understanding of Protein Signaling in Cellular Development

Scientists at Rice University recently found that a protein signaling pathway called WNT, typically associated with its role in early organism development, can both listen for signals from a large amount of triggers and influence cell types throughout embryonic development. These new findings, published in PNAS, add to the already known functions of WNT, deepening our understanding of it and opening the doors to new potential applications of it in stem cell research.

Led by Aryeh Warmflash, Ph. D., researchers discovered that the WNT pathway is different between stem cells and differentiated cells, contrary to prior belief that it was the same for both. Using CRISPR-Cas9 gene editing technology, the Warmflash lab observed that the WNT signaling pathway is actually context-dependent throughout the process of cellular development. This research brings a whole new understanding to the way the WNT pathway operates, and could open the doors to new forms of gene therapy and treatments for diseases like cancers that involve genetic pathway mutations.

People and Places

In a recent article from Technical.ly Philly, named Group K Diagnostics on a list of ten promising startups in Philadelphia. Group K Diagnostics founder Brianna Wronko graduated with a B.S.E. from Penn’s Department of Bioengineering in 2017, and her point-of-care diagnostics company raised over $2 million in funding last year. Congratulations Brianna!

We would also like to congratulate Pamela K. Woodward, M.D., on her being named as the inaugural Hugh Monroe Wilson Professor of Radiology at the Washington University School of Medicine in St. Louis. Also a Professor of Biomedical Engineering at the university, Dr. Woodward leads a research lab with a focus on cardiovascular imaging, including work on new standards for diagnosis of pulmonary blood clots and on an atherosclerosis imaging agent.

Lastly, we would like to congratulate all of the following researchers on their election to the National Academy of Engineering:

  • David Bishop, Ph. D., a professor at the College of Engineering at Boston University whose current research involves the development of personalized heart tissue as an all-encompassing treatment for patients with heart disease.
  • Joanna Aizenberg, Ph. D., a professor of chemistry and chemical biology at Harvard University who leads research in the synthesis of biomimetic inorganic materials
  • Gilda Barabino, Ph. D., the dean of the City College of New York’s Grove School for Engineering whose lab focuses on cartilage tissue engineering and treatments for sickle cell disease.
  • Karl Deisseroth, M.D., Ph. D., a professor of bioengineering at Stanford University whose research involves the re-engineering of brain circuits through novel electromagnetic brain stimulation techniques.
  • Rosalind Picard, Ph.D., the founder and director of the Affective Computing Research Group at the Massachusetts Institute of Technology’s Media Lab whose research focuses on the development of technology that can measure and understand human emotion.
  • And finally, Molly Stevens, Ph. D., the Research Director for Biomedical Material Sciences at the Imperial College of London with research in understanding biomaterial interfaces for biosensing and regenerative medicine.

Bioengineering Welcomes New Faculty Member Sydney Shaffer

Sydney Shaffer, MD, PhD

The Department of Bioengineering at the University of Pennsylvania is proud to announce the appointment of Sydney Shaffer, Ph.D., as an Assistant Professor of Bioengineering. She shares a joint appointment with Pathology and Laboratory Medicine. Originally from Atlanta, GA, Dr. Shaffer received her B.S. in Chemical Engineering from Georgia Institute of Technology, coming to Penn to complete her M.D./Ph.D. work in Bioengineering and the Perelman School of Medicine. After graduating in 2018, she conducted her postdoctoral work at Penn in Cancer Biology with Dr. Junwei Shi.

Dr. Shaffer’s research is is focused on understanding how differences present in single-cells can generate phenotypes such as drug resistance in cancer, oncogenesis, differentiation, and invasion. Our approach leverages cutting-edge technologies including high-throughput imaging, single-molecule RNA FISH, fluorescent protein tagging, CRISPR/Cas9 screening, and flow cytometry to investigate rare single-cell phenomena. Further information can be found at www.sydshafferlab.com.

In addition to her exciting research, Dr. Shaffer will be an enthusiastic new member of the Bioengineering Department community. In the short term, she will be taking over the popular class BE 400 (Preceptorships in Bioengineering) which gives undergraduates the rare chance to shadow renowned physicians over a period of ten weeks. She will also serve as a faculty advisor as well as a mentor to the lucky students in her classes and lab.

Dr. Shaffer says that, “With my research interests and training at the interface of engineering and medicine, I am thrilled to be part of the highly interdisciplinary community of Penn Bioengineering.”

“Sydney has a unique combination of creativity and impact in her work,” says Solomon R. Pollack Professor and Chair Dr. David Meaney. “Her work to untangle the secrets of how single cancer cells can develop resistance to a cancer drug  therefore leading to a return of the cancer  is nothing short of stunning. We are incredibly fortunate to have her on our faculty. ”