A “wiring diagram of the human brain,” produced using diffusion MRI scans of the brain.
A group of four scholars from the University of Pennsylvania, including Bioengineering professor Danielle Bassett, have issued a call in the journal Nature Human Behaviour for greater safeguards for patients as treatments in the field of neuroscience evolve and come ever closer to resembling “mind control.”
“While we don’t believe,” Bassett said, “that the science-fiction idea of mind control, totally overriding a person’s autonomy, will ever be possible, new brain-focused therapies are becoming more specific, targeted and effective at manipulating individuals’ mental states. As these techniques and technologies mature, we need systems in place to make sure they are applied such that they maximize beneficial effects and minimize unwanted side effects.”
As noted earlier this week, Penn BE will be bringing in three new faculty members over the coming academic year, starting with Alex Hughes, who will start in the fall semester. Here’s the first of our series of podcasts with the new faculty, to come each Friday this month. Enjoy!
(P.S. Apologies for the rough version of the audio. We are still learning!)
We are thrilled to announce the successful recruitment of three (!) new faculty members to the department. We conducted a national faculty search and could not decide on one — we wanted all three of our finalists! We are very happy that they chose Penn and think we can provide an amazing environment for their education and research programs.
Alex Hughes, Ph.D.
Alex Hughes, Ph.D., will join us in the Spring 2018 semester. Dr. Hughes comes to us from the University of California, San Francisco (UCSF), where he is a postdoctoral fellow. Alex’s research regards determining what he calls the “design rules” underlying how cells assemble into tissues during development, both to better understand these tissues and to engineer methods to build them from scratch
Lukasz Bugaj, Ph.D.
Lukasz Bugaj, Ph.D., will arrive in the Spring 2018 semester. Dr. Bugaj is also coming here from UCSF following a postdoc, and his work is in the field of optogenetics — a scientific process whereby light is used to alter protein conformation, thereby giving one a tool to manipulate cells. In particular, Lukasz’s research has established the ability to induce proteins to cluster ‘on demand’ using light, and he wants to use these and other new technologies he invented to study cell signaling in stem cells and in cancer.
Mike Mitchell, Ph.D.
Mike Mitchell, Ph.D., will also join us in the Spring 2018 semester after finishing his postdoctoral fellowship at MIT in the Langer Lab. In his research, Dr. Mitchell seeks to engineer cells in the bone marrow and blood vessels as a way of gaining control over how and why cancer metastasizes. Mike’s work has already had impressive results in animal models of cancer. His lab will employ tools and concepts from cellular engineering, biomaterials science, and drug delivery to fundamentally understand and therapeutically target complex biological barriers in the body.
In the coming month, we’ll feature podcasts of interview with each of the new faculty members, as well as with Konrad Kording, so be sure to keep an eye out for those.
A Penn Bioengineering professor, Paul Ducheyne, Ph.D., is the editor-in-chief of the new second edition of Comprehensive Biomaterials II, released by Elsevier on June 1. The seven-volume collection, which Dr. Ducheyne edited along with faculty members from the University of California, Berkeley, Queensland University of Technology (Australia), University of Utah, and Johannes Gutenberg University Medical Center (Germany), collects articles written by experts in the field of biomaterials.
According to Elsevier, the articles “address the current status of nearly all biomaterials in the field, their strengths and weaknesses, their future prospects, appropriate analytical methods and testing, device applications and performance, emerging candidate materials as competitors and disruptive technologies, research and development, regulatory management, commercial aspects, and applications, including medical applications.”
In the preface to the collection, Dr. Ducheyne details how his team and Elsevier worked together to assure the continued high impact of the text by issuing it in both a print version and online via Elsevier’s Science Direct platform. He writes further, “It was the objective of the editorial team to compose the publication with chapters that would provide strategic insights for those working in diverse biomaterials applications, research and development, regulatory management, and industry.”
What a nanoparticle remembers during its journey is pictorially represented in the above figure, and this “memory” is crucial in predicting its approach to the blood vessel wall and its subsequent capture by cell surface receptors, collectively determining the efficacy of therapeutic drug delivery. Reprinted from: Ramakrishnan et al, “Motion of a nano-spheroid in a cylindrical vessel flow: Brownian and hydrodynamic interactions,” J Fluid Mech. 2017;821:117-152, with permission of Cambridge UP, owner of copyright.
A recent article coauthored by Ramakrishnan Natesan, a postdoctoral fellow in the Department of Bioengineering who works in the lab of Dr. Ravi Radhakrishnan, and published in the Journal of Fluid Mechanics provides an elegant and rigorous approach to integrate the memory, errant motion, and adhesion effects in the dynamics of colloidal nanoparticles of different sizes and shapes. The method described in the article computationally analyzes how the hydrodynamic forces are influenced by size, shape, and nature of confining boundary amidst blood flow.
In traditional modes of therapeutic treatment, such as a direct intravenous (IV) injection, only a small fraction of injected drug accesses the diseased tissue. Suboptimal therapeutic delivery represents an acute challenge by limiting the efficacy of biotherapeutics. Strategies to address and overcome this challenge may be based on theoretical and computational approaches to in order to help design innovative, quantitative, experimental methods. Targeted therapeutic delivery using nanoparticles coated with specific targeting molecules is such an approach in therapeutic and diagnostic applications.
Targeted delivery is inherently a multiscale problem: a broad range of length and time scales govern the hydrodynamic, microscopic, and molecular interactions mediating nanoparticle motion in blood flow and capture due to cell binding. The events following upon the injection of a targeted therapeutic nanoparticle bearing a drug (nanocarrier) include flow through blood vessels and maneuvering around much larger entities in the blood, such as the red blood cells. Nanoparticles eventually break free to approach the wall of the blood vessel — a phenomenon collectively known as margination.
After margination, the nanoparticle is relatively free from the influences of the blood cells but starts to “feel” the approach to the wall. It needs to get excruciatingly close to the wall to stick — a phenomenon known as adhesion or capture. In the backdrop of this arduous journey is the inescapable randomness of its motion caused by Brownian forces, an erratic form of motion that only impacts nanoscale objects. The interplay among fluid forces, Brownian fluctuations, and wall interactions shape the detailed itinerary of the nanoparticle. How it moves at a given location and given time is intricately coupled with the motion of the surrounding fluid, namely the blood plasma, which is mostly water. Together, they decide to pave the path forward in time described by a “memory function.”
“The optimization of future drug delivery agents, such as targeted therapeutic nanocarriers, could be based on our computations,” Dr. Ramakrishnan says. “This will, in effect, establish a rational computational platform for fast tracking the clinical translation from carrier design to clinical practice.”
The National Institutes of Health (NIH) has awarded a grant to Brian Chow, Ph.D., an assistant professor in the Department of Bioengineering, to study ultrafast genetically encoded voltage indicators (GEVIs). GEVIs are proteins that can detect changes in the electrical output of cells and report those changes by emitting different color light. His research seeks to create GEVIs that can report these changes much more rapidly – in fact, more than a million times more quickly than the velocity of the changes themselves – and apply these ultrafast GEVIs to the study of the brain.
The NIH-funded research will build on earlier research, employing de novo fluorescent proteins (dFPs) created in Dr. Chow’s lab. These dFPs, which are totally artificial and unrelated to natural proteins, report voltage changes in neurons by changing in brightness. Working with a team of investigators that includes faculty members from the Departments of Biochemistry & Biophysics and Neuroscience, Dr. Chow hopes to develop these ultrafast GEVIs.
“Monitoring thousands of neurons in parallel will shed new light on cognition, learning and memory, mood, and the physiological underpinnings of nervous system disorders,” he says.
Dan Huh, Wilf Family Term Assistant Professor in the Penn Department of Bioengineering, has received the Cancer Research Institute (CRI) Technology Impact Award. Dr. Huh, whose research attempts to model cancer-immune cell interactions in microphysiological systems, will receive $1 million over the next three years for direct costs of his research.
“This award will provide us with an exciting opportunity to explore the potential of our organ-on-a-chip technology for the study of cancer immunotherapy, which is one of the most promising yet poorly understood clinical strategies for cancer treatment,” Dr. Huh said. “I am honored to receive this major award and excited with the prospect of contributing to this rapidly emerging area of medicine using innovative bioengineering technologies.”
New research by faculty in the University of Pennsylvania Department of Bioengineering is examining the interplay between cells and their environment and how they impact the cells’ ability to grow and spread, showing that stiffness is not the only factor researchers should consider when studying this process.
The relationship between cellular adhesion and spread is a key factor in cancer metastasis. Better understanding of this dynamic would improve diagnosis of the disease and provide a potential target in combating it; reducing the ability of cells to grip their environment could keep them contained.
Vivek Shenoy (left) and Jason Burdick
The study, published in the Proceedings of the National Academy of Sciences, was led by Vivek Shenoy, professor in the Department of Materials Science and Engineering, co-director of Penn’s Center for Engineering Mechanobiology, and a secondary faculty member in the Department of Bioengineering, along with Xuan Cao and Ehsan Ban, members of his lab. They collaborated with Jason Burdick, professor in the Department of Bioengineering, Boston University’s Christopher Chen, the University of Michigan’s Brendon Baker and the University of Hong Kong’s Yuan Lin.
This collaboration reflects work of The Center for Engineering Mechanobiology, a National Science Foundation-funded Science and Technology Center that supports interdisciplinary research on the way cells exert and are influenced by the physical forces in their environment.
Previous work from Shenoy’s group has shown that the relationship between cancer cells and the extracellular matrix is dynamic, containing feedback mechanisms that can change the ECM’s properties, including overall stiffness. One earlier study investigated how cancer cells attempt to strike a balance in the density of the fibrous netting surrounding them. If there are too few fibers to grip, the cells can’t get enough traction to move. If there are too many, the holes in the net become too small for the cells to pass through.
Danielle Bassett, Eduardo D. Glandt Faculty Fellow and Associate Professor in the departments of Bioengineering and Electrical and Systems Engineering, recently collaborated with colleagues from the Perelman School of Medicine on a study that looks at how brain networks change as children develop into adolescence. Bassett’s previous work on applying network science principles to neuroscience has suggested that the organization of these networks helps lead to “cognitive control” and that they reorganize as children age, improving executive function.
In a new paper published in Current Biology, Bassett and her colleagues delve deeper into the network changes that lead to this improvement.
“The work,” Bassett says, “significantly extends our understanding of the role of modular network organization in development, and its importance for executive function.”
Susan S. Margulies, Ph.D., currently professor of bioengineering at the University of Pennsylvania, has been named the Wallace H. Coulter Chair of the Department of Biomedical Engineering at Georgia Tech/Emory University and the Georgia Research Alliance Eminent Scholar in Injury Biomechanics. Her appointment begins August 1.
Dr. Margulies’s history at Penn goes back to 1982, she arrived at Penn to earn a master’s degree in the bioengineering department, followed by her Ph.D. in 1987. In 1993, she returned to Penn as an assistant professor, with promotion to associate in 1998 and full professor in 2004.
“At GT-Emory BME I will lead 72 faculty and 1,500 students, and look forward to creating impact in a new environment,” Dr. Margulies says. “As a Penn alum and emeritus faculty member, my ties here run deep. I look forward to keeping in touch.”
Dr. Margulies’s has deep roots at Penn indeed, and her accomplishments are broad and distinctive. They include:
Creating new faculty mentoring programs across the university, including the Penn Faculty Pathways program
Teaching a broad number of courses spanning Introduction to Bioengineering through to Pedagogical Methods in Engineering Education
Establishing many new research initiatives that extended into Children’s Hospital of Philadelphia and significant relationships with industry
Activity with several national leadership positions
On Dr. Margulies’s departure, David Meaney, the department chair, said, “We will miss Susan’s wisdom and insight, but we wish her the very best in her next step.”
