One way to measure the success or influence of a researcher is to consider how many times they’re cited by other researchers. Every published paper requires a reference section listing relevant earlier papers, and the Web of Science Group keeps track of how many times different authors are cited over the course of a year.
Danielle Bassett, Ph.D.
In 2019, two members of the Penn Bioengineering department, Jason Burdick, Ph.D., and Danielle Bassett, Ph.D., were named Highly Cited Researchers, indicating that each of them placed within the top 1% of citations in their field based on the Web of Science’s index. For the past year, only 6,300 researchers were recognized with this honor, a number that makes up a mere 0.1% of researchers worldwide. Bassett’s lab looks at the use of knowledge, brain, and dynamic networks to understand bioengineering problems at a systems-level analysis, while Burdick’s lab focuses on advancements in tissue engineering through polymer design and development.
Jason Burdick, PhD
Burdick’s and Bassett’s naming to the list of Highly Cited Researchers demonstrates that their research had an outsized influence over current work in the field of bioengineering in the last year, and that new innovations continue to be developed from foundations these two Penn researchers created. To be included among such a small percentage of researchers worldwide indicates that Bassett and Burdick are sources of great impact and influence in bioengineering advancements today.
Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!
Speaker: Tara L. Deans, Ph.D.
Assistant Professor
Biomedical Engineering
University of Utah
Date: Thursday, March 5, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building
Title: “Engineering Stem Cells to Create Novel Delivery Vehicles”
Abstract:
Synthetic biology has transformed how cells can be reprogrammed, providing a means to reliably and predictably control cell behavior with the assembly of genetic parts into more complex gene circuits. Using approaches and tools in synthetic biology, we are programming stem cells with novel genetic tools to control genes and pathways that result in changes in stem cell fate decisions, in addition to reprogramming terminally differentiated cells to function as unique therapeutic diagnostic and delivery vehicles.
Bio:
Dr. Tara Deans received her PhD from Boston University in Biomedical Engineering. Following her postdoctoral training at Johns Hopkins University, she became an Assistant Professor in Biomedical Engineering at the University of Utah. Currently, Dr. Deans runs an applied mammalian synthetic biology laboratory where her lab focuses on building novel genetic tools to study the mechanisms of stem cell differentiation for the purpose of directing cell fate decisions. Recently, Dr. Deans received four prestigious awards to support this area of research: the NSF CAREER Award, the Office of Naval Research (ONR) Young Investigator Award, the NIH Trailblazer Award and an NIH Director’s New Innovator Award. In addition to her research, Dr. Deans was recently named a STEM Ambassador in the STEM Ambassador Program (STEMAP) at the University of Utah to engage underrepresented groups in STEM fields.
Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!
Michael Yaszemski, M.D., Ph.D.
Speaker: Michael Yaszemski, M.D., Ph.D.
The Krehbiel Endowed Professor of Orthopedic Surgery and Biomedical Engineering
Mayo Clinic
Date: Thursday, February 27, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building
Title: “Musculoskeletal Tissue Engineering”
Abstract:
The field of Tissue Engineering/Regenerative Medicine is replete with advances that have been translated to human use. However, our job is not done when a treatment for a specific disease or traumatic event has been invented and translated to humans. In order to be available to the population nationwide (or globally), our novel treatment must be manufactured, transported to the user, and administered by a physician to that user. In addition, novel treatments for rare diseases may not be amenable to manufacture by a company, and perhaps would be best manufactured by an academic medical center. I will discuss these issues that occur after successful translation of a novel treatment to human use, as well as potential strategies to address them.
Bio:
Dr. Michael Yaszemski is the Krehbiel Family Endowed Professor of Orthopedic Surgery and Biomedical Engineering at Mayo Clinic and director of its Polymeric Biomaterials and Tissue Engineering Laboratory. He is a retired USAF Brigadier General. He has served as the president of the Mayo medical staff. He received both bachelor’s and master’s degrees in chemical engineering from Lehigh University in 1977 and 1978, an M.D. from Georgetown University in 1983 and a Ph.D. in chemical engineering from Massachusetts Institute of Technology in 1995. He served as a member of the Lehigh University Board of Trustees.
The George H. Stephenson Foundation Educational Laboratory and Bio-MakerSpace, more commonly known as the Bio-MakerSpace, has recently become a hub for Penn student start-ups that continue after graduation. Beyond offering a home base for projects by Bioengineering majors, the lab is also open to Penn students, regardless of major. Unlike other departmental undergraduate labs, the Bio-MakerSpace encourages interdisciplinary projects and collaborations from students across all different majors.
Even better, the lab has a neutral policy when it comes to intellectual property (IP), meaning all IP behind student projects belongs to the students instead of the lab or the engineering school. With a wide variety of prototyping equipment, coding and software programs installed on lab computers, and an extremely helpful lab staff, the Bio-MakerSpace provides students of all academic backgrounds the resources to turn their ideas into realities or even businesses, as a recent succession of start-ups founded in the lab has shown.
One of the most successful start-ups to come out of the Bio-MakerSpace in the last few years is Group K Diagnostics, founded by 2017 Bioengineering alumna Brianna Wronko. The company focuses on the use of a point-of-care diagnostic device called KromaHealthTM. Offering a variety of different tests based on the input of a small amount of blood, serum, or urine, the device induces a color change through a series of reactions that can be detected through image processing. Developed in part from Wronko’s senior design project (hence the name “Group K”) and in part from her experience working at an HIV clinic, Group K Diagnostics looks to expand access to care for all populations.
But not all start-ups from the Bio-MakerSpace have origins in senior design projects. Three start-ups from 2019, two of which won the Penn President’s Innovation Prize, all began as independent initiatives from students. InstaHub, founded by 2019 Wharton alumnus Michael Wong with help from Bioengineering doctoral candidate Dayo Adewole, is a company that focuses on the use of snap-on automation for light energy conservation. A simple and easy-to-install device with motion and occupancy sensors, InstaHub aims to reduce energy consumption in a way that’s simpler and cheaper than rewiring projects that might otherwise be required. Here, Adewole shares the way that access to the Bio-MakerSpace provided InstaHub with a helpful platform.
The second start-up from 2019 to come out of the Bio-MakerSpace and win a President’s Innovation Prize is Strella Biotechnology, founded by recent graduate Katherine Sizov (Biology 2019). In developing sensors with the ability to detect ethylene gas emitted by rotting fruits, Strella hopes to reduce the immense amount of food waste due to produce simply going bad in storage. With a patent-pending biosensor that mimics the way ripe fruits detect ethylene emissions of nearby rotting fruits, the technology behind Strella involves both biology and aspects of engineering. In this video, Sizov herself talks about the way that the Bio-MakerSpace opened its doors to her, and allowed her work to really take off with the help of resources she wouldn’t have easily found otherwise.
Yet another start-up to use the Bio-MakerSpace as a launch pad for innovation is BioAlert Technologies, comprised of a group of Penn engineering undergraduate and graduate students, including 2019 Bioengineering alumnus Johnny Forde and current Biotechnology student Marc Rosenberg, who is the startup’s CEO and founder. BioAlert’s innovations are in what they call continuous infection monitoring (CIM) systems, designed to detect infections in patients with diabetic foot ulcers. Often, even when properly bandaged by a doctor, these ulcers run the risk of bacterial infection once a patient returns home and continues to care for the wound. BioAlert uses their platform to assess whether or not a bacterial infection might occur in a given patient’s wound, and uses an app to alert both patients and doctors of it, so that patients can receive the proper response treatment and medication as quickly as possible.
Though each of these start-ups used the resources of the Bio-MakerSpace, they are each interdisciplinary approaches to solving real-world problems today. Paired with other student resources at Penn like courses offered under an Engineering Entrepreneurship minor, knowledge from the nearby Wharton business school professors, and competitions like the Rothberg Catalyzer, the Bio-MakerSpace allows for any student to transform their idea into a reality, and potentially take it to market.
Imagine if a computer could learn from molecules found in nature and use an algorithm to generate new ones. Then imagine those molecules could get printed and tested in a lab against some of the nastiest, most dangerous bacteria out there — bacteria quickly becoming resistant to our current antibiotic options.
Or consider a bandage that can sense an infection with fewer than 100 bacterial cells present in an open wound. What if that bandage could then send a signal to your phone letting you know an infection had started and asking you to press a button to trigger the release of the treatment therapy it contained?
These ideas aren’t science fiction. They’re projects happening right now, in various stages, in the lab of Penn synthetic biologist César de la Fuente, who joined the University as a Presidential Professor in May 2019. His ultimate goal is to develop the first computer-made antibiotics. But beyond that, his lab — which includes three postdoctoral fellows, a visiting professor, and a handful of graduate students and undergrads — has many other endeavors that sit squarely at the intersection of computer science and microbiology.
Computer-generated antibiotics
Antibiotic resistance is becoming a dangerous problem, both in the United States and worldwide. According to the Centers for Disease Control and Prevention, each year in the U.S., at least 2.8 million people get infections that antibiotics can’t help, and more than 35,000 die from those infections. Around the world, common ailments like pneumonia and food-borne illness are getting harder to treat.
De la Fuente earned his bachelor’s degree in biotechnology, then a doctorate in microbiology and immunology and a postdoc in synthetic biology and computational biology. Combining these fields led him to the innovative work his lab does today.
New antibiotics are needed, and according to de la Fuente, it’s time to look beyond the traditional approach.
“We’ve relied on nature as a source of antibiotics for many, many years. My whole hypothesis is that nature has perhaps run out of inspiration,” says de la Fuente, who has appointments in the Perelman School of Medicine and the School of Engineering and Applied Science. “We haven’t been able to discover any new scaffolds for many years. Can we digitize that information, nature’s chemistry, to be able to create and discover new molecules?”
To do that, his team turned to amino acids, the building blocks of protein molecules. The 20 that occur naturally bond in countless sequences and lengths, then fold to form different proteins. The sequencing possibilities are expansive, more than the number of stars in the universe. “We could never synthesize all of them and just see what happens,” says postdoc Marcelo Melo. “We have to combine the chemical knowledge — decades of chemistry on these tell us how they behave — with the computational side, because a computer can find patterns unlike any human could.”
Using machine learning, the researchers provide the computer with natural molecules that successfully work against bacteria. The computer learns from those examples, then generates new, artificial molecules. “We try this back and forth and hopefully we find patterns, new patterns that we can explore, instead of blindly searching,” Melo says.
The computer can then test each artificial sequence virtually, setting aside the most successful components and tossing the rest, in a form of computational natural selection. Those pieces with the highest potential get used to create new sequences, theoretically producing better and better ones each time.
De la Fuente’s team has seen some promising results already: “A lot of the molecules we’ve synthesized have worked,” he says. “The best ones worked in animal models. They were able to reduce infections in mice — which was pretty cool, given that the computer generated the whole thing.” Still, de la Fuente says the work is years away from producing anything close to a shelf-ready antibiotic.
An artist’s illustration of nanoparticles transporting mRNA into a T cell (blue), allowing the latter to express surface receptors that recognize cancer cells (red). (Credit: Ryan Allen, Second Bay Studios)
New cancer immunotherapies involve extracting a patient’s T cells and genetically engineering them so they will recognize and attack tumors. This type of therapy is not without challenges, however. Engineering a patient’s T cells is laborious and expensive. And when successful, the alterations to the immune system immediately make patients very sick for a short period of time, with symptoms including fever, nausea and neurological effects.
Now, Penn researchers have demonstrated a new engineering technique that, because it is less toxic to the T cells, could enable a different mechanism for altering the way they recognize cancer, and could have fewer side effects for patients.
The technique involves ferrying messenger RNA (mRNA) across the T cell’s membrane via a lipid-based nanoparticle, rather than using a modified HIV virus to rewrite the cell’s DNA. Using the former approach would be preferable, as it only confers a temporary change to the patient’s immune system, but the current standard method for getting mRNA past the cell membrane can be too toxic to use on the limited number of T cells that can be extracted from a patient.
Michael Mitchell, Margaret Billingsley, and Carl June
The researchers demonstrated their technique in a study published in the journal Nano Letters. It was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation of bioengineering in the School of Engineering and Applied Science, and Margaret Billingsley, a graduate student in his lab.
They collaborated with one of the pioneers of CAR T therapy: Carl June, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and the director of the Parker Institute for Cancer Immunotherapy at the Perelman School of Medicine.
We would like to congratulate Assistant Professor in Bioengineering Alex Hughes, Ph.D., on receiving the Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health (NIH), which funds investigators to create flexible and forward-thinking research programs. Hughes is the first recipient of this award in Penn’s School of Engineering and Applied Science, marking a major accomplishment for him and his lab.
The award recognizes Hughes’ efforts to create new tools used for tissue engineering, in particular by fusing concepts from developmental biology into tissue construction efforts. Hughes believes this approach will have impacts on fundamental understanding human disease, leading to new strategies to combat them. Hughes and his lab specifically focus on kidney disease. As Hughes says, “defects in the kidney and urinary tract account for up to a third of all birth defects.” Furthermore, because kidney development involves many different kinds of cell interactions, there’s a gap in understanding exactly how these defects occur.
Unlike other grants that focus on funding projects, the MIRA prioritizes the people behind the research, giving them funding as a sign of faith in the future work they’ll choose to do. “The MIRA has allowed us significant leeway to integrate several complementary approaches here,” Hughes says. Because of this flexibility, Hughes and his lab thinks it will allow them to reach for more innovative and risky approaches in their research, in the hopes that this will lead to a better understanding of kidney defects and modes of treatment for them.
University of Washington Researchers Engineer a New Way to Study Circulatory Obstruction
Capillaries are one of the most important forms of vasculature in our body, as they allow our blood to transfer nutrients to other parts of our body. But for how much effect capillary functionality can have on our health, their small size makes them extremely difficult to engineer into models for a variety of diseases. Now, researchers at the University of Washington led by Ying Zheng, Ph. D., engineered a three-dimensional microvessel model with living cells to study the mechanisms of microcirculatory obstruction involved with malaria.
Rather than just achieving a physical model of capillaries, these researchers created a model that allowed them to study typical flow and motion through capillaries, before comparing it to deficiencies in this behavior involved with diseases like malaria. The shape of the engineered model is similar to that of an hourglass, allowing the researchers to study instances where red blood cell transit may encounter bottlenecks between the capillaries and other vessels. Using multiphoton technology, Zheng and her team created 100mm capillary models with etched-in channels and a collagen base, to closely model the typical size and rigidity of the vessels. Tested with malaria-infected blood cells, the model showed similar circulatory obstructive behavior to that which occurs in patients, giving hope that this model can be transferred to other diseases involving such obstruction, like sickle cell anemia, diabetes, and cardiovascular conditions.
Understanding a Cell Membrane Protein Could Be the Key to New Cancer Treatments
Almost every cell in the body has integrins, a form of proteins, on its membrane, allowing cells to sense biological information from beyond their membranes while also using this feedback information to initiate signals within cells themselves. Bioengineers at the Imperial College of London recently looked at the way another membrane protein, called syndecan-4, interacts with integrins as a potential form of future cancer treatment. Referred to as “cellular hands” by lead researcher of the study Armando del Rio Hernandez, Ph.D., syndecan-4 sometimes controls the development of diseases or conditions like cancer and fibrosis. Hernandez and his team specifically studied the ties of syndecan-4 to yes-associated protein (YAP) and enzyme called P13K, both of which are affiliated with qualities of cancer progression like halted apoptosis or cell stiffening. Knowing this, Hernandez and his team hope to continue research into understanding the mechanisms of syndecan-4 throughout the cell, in search of new mechanisms and targets to focus on with future developments of cancer treatments.
A New Medical Device Could Improve Nerve Functionality After Severe Damage
Serious nerve damage remains difficult to repair surgically, often involving the stretching of nerves for localized damage, or the transfer of healthy nerve cells from another part of the body to fill larger gaps in nerve damage. But these imperfect solutions limit the return of full nerve function and movement to the damaged part of the body, and in more serious cases with large areas of nerve damage, can also risk damage in other areas of the body that healthy nerves are borrowed from for treatment. A new study from the University of Pittsburgh published in Science Translational Medicine led by Kacey Marra, Ph. D., has successfully repaired nerve damage in mice and monkeys using a biodegradable tube that releases growth factors called glial-cell-derived neurotrophic factors over time.
Marra and her team showed that this new device restored nerve function up to 80% in nonhuman primates, where current methods of nerve replacement often only achieve 50-60% functionality restoration. The device might have an easier time getting FDA-approval, since it doesn’t involve the use of stem cells in its repair mechanisms. Hoping to start human clinical trials in 2021, Marra and her team hope that the device will help both injured veterans and typical patients with nerve damage, and see potential future applications in facial nerve damage as well.
A New Computational Model Could Improve Treatments for Cancer, HIV, and Autoimmune Diseases
With cancer, HIV, and other autoimmune diseases, the best treatment options for patients are often determined with trial-and-error methods, leading to prolonged instances of ineffective approaches and sometimes unnecessary side effects. A group of researchers led by Wesley Errington, Ph.D., at the University of Minnesota decided to take a computational approach this problem, in an effort to more quickly and efficiently determine the most appropriate treatment for a given patient. Based on parameters controlling interactions between molecules with multiple binding sites, the team’s new model looks primarily at binding strength, linkage rigidity, and size of linkage arrays. Because diseases can often involve issues in molecular binding, the model aimed to model the 78 unique binding configurations for cases of when interacting molecules only have three binding sites, which are often difficult to observe experimentally. This new approach will allow for faster and easier determination of treatments for patients with diseases involving these molecular interactions.
Improved Drug Screening for Glioblastoma Patients
A new microfluidic brain chip from researchers at the University of Houston could help improve treatment evaluations for brain tumors. Glioblastoma patients, who have a five-year survival rate of a little over 5%, are some of the most common patients suffering from malignant brain tumors. This new chip, developed by the lab of Yasemin Akay, Ph.D., can quickly determine cancer drug effectiveness by analyzing a piece of cultured tumor biopsy from a patient by incorporating different chemotherapy treatments through the microfluidic vessels. Overall, Akay and her team found that this new chip holds hope as a future efficient and inexpensive form of drug screening for glioblastoma patients.
People and Places
The brain constructs maps to guide people, not just of physical spaces but also to connect stimuli around them, like conversations and other people. It’s long been known that the brain area responsible for this spatial navigation—the medial temporal lobe—is also involved in recalling memories.
Michael Kahana (left) is principal investigator in the Defense Advanced Research Projects Agency’s RAM program and a professor in the Department of Psychology. Ethan Solomon is an M.D./Ph.D. student in the Department of Bioengineering of the School of Engineering and Applied Science and in the Perelman School of Medicine.
Now, neuroscientists at the University of Pennsylvania have discovered that the signals the brain produces during spatial navigation and episodic memory recall look similar. Low-frequency brain waves called the theta rhythm appear as people jump from one memory to the next, as many prior studies looking only at human navigation have shown. The new findings, which suggest that the brain structures responsible for helping people navigate the world may also “navigate” a mental map of prior experiences, appear in the Proceedings of the National Academy of Sciences.
The Florida Institute of Technology recently announced plans to start construction in spring 2020 on a new Health Sciences Research Center, set to further establish biomedical engineering and pre-medical coursework and research at the institute. With plans to open the new center in 2022, Florida Tech anticipates increased enrollment in the two programs, and hopes that the center will offer more opportunities in a growing professional field.
Anson Ong, Ph.D., the Associate Dean of Administration and Graduate Programs at the University of Texas at San Antonio, was recently elected to the International College of Fellows of Biomaterials Science and Engineering. With a focus on research in biomaterial implants for orthopaedic applications, Ong’s election to the college honors his advancement and contribution to the field of biomaterials research.
Our next Penn Bioengineering seminar is coming up soon. We hope to see you there!
Jeffrey J. Tabor, Ph.D.
Speaker: Jeffrey J. Tabor, Ph.D.
Associate Professor of Bioengineering and BioSciences
Rice University
Date: Thursday, February 13, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building
Title: “Repurposing bacterial two-component systems as sensors for synthetic biology applications”
Abstract:
Two-component systems (TCSs) are the largest family of signal transduction pathways in biology, and a treasure trove of biosensors for engineering applications. Though present in plants and other eukaryotes, TCSs are ubiquitous in bacteria. Bacteria use TCSs to sense everything from metal ions to carbohydrates and light, and activate responses such as biofilm formation, antibiotic-resistance, and virulence. Despite their importance, the vast majority of TCSs remain uncharacterized. The major challenges are that most bacteria cannot be cultured nor genetically manipulated in the laboratory, and that many TCSs are silenced by poorly-understood gene regulatory networks in laboratory conditions. We have recently developed synthetic biology technologies to address these challenges. In particular, we have developed dual inducible promoter systems that allow us simultaneously express both TCS proteins to optimal levels in the model Gram-negative and Gram-positive bacteria E. coli and B. subtilis. In addition, we have developed a method to modularly interchange the DNA-binding domains of response regulator proteins, enabling unknown or silent TCS output promoters to be replaced with well-characterized alternatives. Finally, we have developed a method to rationally tune the amount of input signal required to activate a TCS over several orders of magnitude by introducing mutations that specifically alter the intrinsic phosphatase activity of the sensor histidine kinase protein. Using these methods, we have repurposed cyanobacterial TCSs to function as optogenetic tools with wavelength specificities from the ultraviolet (380 nm) to the near infrared (770 nm), engineered gut bacteria that diagnose colon inflammation in mice, and discovered a novel pH-sensing TCS in the genome of Yersinia pestis, the causative agent of bubonic plague. Additionally, we have constructed a library of >500 uncharacterized TCSs from the human gut microbiome, which we are screening for novel sensors of gut metabolites and diseases in humans. Finally, we are using our methods to develop new anti-virulence compounds that inhibit TCSs that regulate pathogenesis in major human pathogens. Our work is accelerating fundamental microbiological discoveries and has broad applications in synthetic biology.
Bio:
Since coming to Rice in 2010, Tabor’s work at the interface of synthetic chemistry and molecular/cell biology has led to more than 30 peer-reviewed journal publications and five patent applications. Additional awards he has received include a Collaborative Research Award from the John S. Dunn Foundation (2016), a Michel Systems Biology Innovation Award (2013), a Hamill Innovation Award (2011) by Rice’s Institute of Biosciences and Bioengineering, and a National Academies Keck Futures Initiative (NAKFI) award (2009). Tabor is an affiliated investigator of the NSF Synthetic Biology Engineering Research Center (SynBERC), a member of the editorial board of ACS Synthetic Biology, and has served on an NIH study section and five NSF panels. He also co-organized Synthetic Biology 5.0 – the leading conference in the field.
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.
Speaker: Tara L. Deans, Ph.D.
The 
Capillaries are one of the most important forms of vasculature in our body, as they allow our blood to transfer nutrients to other parts of our body. But for how much effect capillary functionality can have on our health, their small size makes them extremely difficult to engineer into models for a variety of diseases. Now, researchers at the University of Washington led by 
