Cell signaling and the proteins involved in it participate in virtually every process in the body, whether normal or pathological. Much of this signaling involves proteins called cytokines, and of particular interest among them are tumor necrosis factors (TNFs), whose job it is to carry out apoptosis — the process by which cells die at predetermined time points as part of their normal life cycle. Among this family of cytokines, TNF-related apoptosis-inducing ligand (TRAIL) has been of particular interest to oncologists.
The process by which TRAIL combines with or binds to other molecules that modulate the life cycle of cancer cells can interfere with the ability of these molecules to facilitate the growth of cancer cells into tumors. However, attempts to deploy the cytokine to interfere in the process that produces cancer have been unsuccessful because of issues regarding inefficient delivery of TRAIL to the relevant sites, poor circulation of the cytokine in the blood, and the development of resistance to TRAIL. Bioengineers have been hard at work attempting to overcome these barriers.
In a new article published in ACS Nano coauthored by Michael J. Mitchell, Ph.D., Skirkanich Assistant Professor of Innovation at Penn Bioengineering, and Robert Langer, Ph.D., David H. Koch Institute Professor at MIT, these engineered solutions are reviewed and assessed. The review covers nanoparticle technologies with potential to solve the problems encountered thus far, including a range of materials (polymers, lipids, inorganic), cell-nanoparticle hybrids, and therapeutic cells genetically engineered using nanoparticles.
“The TRAIL protein is a essential component of our immune system,” Dr. Mitchell says, “and it kills tumor cells without harming normal ones. However, it remains challenging to deliver the protein into tumors, and tumors can also be resistant to the protein. We and others are now exploiting nanotechnology, genetic engineering, and immune cell-biomaterial hybrids to overcome these key biological barriers to cancer therapy.”
The sheer complexity of the human brain means that, despite the tremendous advances made in neuroscience, there is still much we don’t know about what goes on inside our heads and how it goes awry in mental disorders. Even with the most advanced techniques, much of what we’ve learned about the brain is descriptive — telling that something is different between health and unhealthy function — but not why that something is different or how we could change it.
Among the approaches that have provided important insights into these questions is network science, which seeks to understand the brain as a complex system of multiple interacting components. Now, in a review published recently in Neuron, Danielle Bassett, Ph.D., Eduardo D. Glandt Faculty Fellow and Associate Professor of Bioengineering, and Richard Betzel, Ph.D., a postdoc in Dr. Bassett’s lab, have collaborated with scientists from the University of Heidelberg in Germany. The review covers a broad range of discoveries and innovations, moving from earlier, two-dimensional approaches to understanding the brain, such as graph theory, to newer approaches including multilayer networks, generative network models, and network control theory.
“Stating what is different in brain networks of individuals with disorders of mental health is not the same as identifying why” says Bassett. “Here we propose that emerging tools from network science can be used to identify true mechanisms of mental health disorders, and bridge molecular and genetic mechanisms through brain physiology, thus informing interventions in the form of pharmacological manipulations and brain stimulation.”
Michael Mitchell, Ph.D., who will arrive in the Spring 2018 semester as assistant professor in the Department of Bioengineering, is the first author on a new review published in Nature Reviews Cancer on the topic of engineering and the physical sciences and their contributions to oncology. The review was authored with Rakesh K. Jain, Ph.D., who is Andrew Werk Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School, and Robert Langer, Sc.D., who is Institute Professor in Chemical Engineering at the David H. Koch Institute for Integrative Cancer Research at MIT. Dr. Mitchell is currently in his final semester as a postdoctoral fellow at the Koch Institute and is a member of Dr. Langer’s lab at MIT.
The review focuses on four key areas of development for oncology in recent years: the physical microenvironment of the tumor; technological advances in drug delivery; cellular and molecular imaging; and microfluidics and microfabrication. Asked about the review, Dr. Mitchell said, “We’ve seen exponential growth at the interface of engineering and physical sciences over the last decade, specifically through these advances. These novel tools and technologies have not only advanced our fundamental understanding of the basic biology of cancer but also have accelerated the discovery and translation of new cancer therapeutics.”