Jason Burdick, Ph.D., professor in the Department of Bioengineering, was among the recent recipients of a grant from Sharing Partnership for Innovative Research in Translation (SPIRiT), a pilot grant program awarded by the Clinical and Translational Science Award (CTSA) division of the National Institutes of Health (NIH).
Dr. Burdick’s research, undertaken with Albert Sinusas, MD, of Yale, concerns the development of a noninvasive treatment to limit the damage to the heart caused by heart attacks, which are suffered annually by almost 750,000 Americans. Using single-photo emission computed tomography (SPECT), the technique identifies the damaged heart muscle on the basis of enzymes activated by damage, followed by the targeted administration of bioengineered hydrogels for the delivery of therapeutics
Dr. Burdick says, “This research has the potential to advance treatments for the many individuals with heart attacks who have few current options. Our approach uses injectable materials and advanced imaging techniques to address the changes in protease levels after heart attacks that can lead to tissue damage.”
In other news, Dr. Burdick was one of 12 researchers named by the NIH’s Center for Engineering Complex Tissues to lead collaborative projects aimed at generating complex tissues for several parts of the body.
As we reported earlier, Dan Huh, Wilf Family Term Chair & Assistant Professor in the Department of Bioengineering, has been awarded a $1 million grant from the Cancer Research Institute (CRI), along with its first CRI Technology Impact Award.
Recently, the Penn Engineering Blog featured a story on Dr. Huh’s grant and the research it will support for the next three years. You can read the story at the SEAS blog.
Here’s the promised interview with new faculty member Mike Mitchell, who starts as assistant professor of bioengineering at Penn in the Spring 2017 semester. Mike and editor Andrew E. Mathis discuss Mike’s background and education, where cancer research is now and where it’s heading, and just how big the radius is on the cheesesteak zone of impact around Philadelphia.
Uncertainty is part of life, but the underlying neuroscience of how we make decisions under conditions of uncertainty is only beginning to be understood. In a paper published Monday by Nature Human Behaviour, new Penn Bioengineering faculty member and Penn Integrates Knowledge Professor Konrad Kording, Ph.D., and his coauthor, Iris Vilares, Ph.D., of University College London, offer additional evidence that dopamine lies at the heart of how the brain operates when there is a lack of certainty.
Drs. Kording and Vilares devised a simple computerized test that examined the extent to which test takers relied on previous knowledge vs. what they saw at the present moment. They then administered the test to a cohort of patients with Parkinson’s disease, a condition associated with depleted dopamine levels. The patients were tested both while taking dopaminergic medication and while off it. They found that dopaminergic medication caused the patients to pay greater attention to sensory (i.e., visual) information — an effect that diminished as the patients learned. Ultimately, the study provided evidence that dopamine levels were related to the tendency to rely on new information, also called likelihood uncertainty.
“Scientists believe that understanding uncertainty is key to understanding how the brain computes,” Dr. Kording says. “There are many theories in this space. We provide fairly clean evidence for one of them, which is that dopamine encodes likelihood uncertainty. This information could change the way people think about the manner in which the brain deals with uncertainty.”
Dennis E. Discher, Ph.D., Robert D. Bent Professor in the Department of Chemical and Biomolecular Engineering and a secondary faculty member in the Department of Bioengineering, was the lead author on a recent study that showed that engineered macrophages (a type of immune cell) could be injected into mice, circulate through their bodies, and invade solid tumors in the mice, engulfing human cancers cells in the tumors.
According to Cory Alvey, a graduate student in pharmacology who works in Professor Discher’s lab and the first author on the paper, said, “Combined with cancer-specific targeting antibodies, these engineered macrophages swarm into solid tumors and rapidly drive regression of human tumors without any measurable toxicity.”
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.”
