Writing

Cancer Treatment Goes Local

~ saracody

In two studies, Grinstaff offers new therapeutic approaches to mesothelioma and esophageal cancer

When it comes to treating cancer, one Boston University researcher is going local. Mark Grinstaff, a BU College of Engineering professor of biomedical engineering and materials science and engineering, published two studies in January 2016 that offer new approaches to the treatment of two intractable cancers—mesothelioma and esophageal cancer—by delivering therapeutic agents directly to the tumor site.

“Local drug delivery allows us to maximize drug dose at the disease site while reducing drug exposure to the rest of the body,” says Grinstaff, who is also a professor of chemistry and of medicine. “This approach affords significantly fewer negative side effects, like hair loss and an overall decrease in the immune system, which are common with conventional intravenous chemotherapy treatments.”

The first study, published in Scientific Reports, describes a highly targeted approach to treating mesothelioma, an aggressive and highly fatal cancer associated with asbestos exposure. Mesothelioma progresses locally, Grinstaff noted, and current chemotherapy treatments—which infuse toxic drugs throughout the body for a relatively brief period—have not been effective in extending survival.

Postdoctoral research associate Aaron Colby (ENG’09, ’14) prepared 100-nanometer particles that were small enough to enter a cancer cell, but expanded to 1,000 nanometers once exposed to the cell’s low pH level. In addition, the nanoparticles were engineered to attract a chemotherapy drug and draw it away from healthy cells through a process similar to that which causes oil to separate from vinegar. With the particles acting as beacons for the chemotherapy and the cancer cells unable to expel them quickly, the drug spent more time on target while avoiding healthy tissue.

“In our strategy, we are sending in a nanoparticle first and the drug second, which we have found to increase the amount of drug delivered to the tumor itself compared to the current treatment method,” says Colby.

The second study, published in Angewandte Chemie International Edition, reports a novel drug delivery technology to treat esophageal cancer. A common problem that arises with esophageal cancer patients is difficulty swallowing, as a result of the tumor narrowing or blocking the esophagus. Doctors insert a wire mesh stent to open the passageway.

Grinstaff and his research team had the idea to integrate drug delivery with this tool as a one-two punch to focus the drug on the problem itself. Graduate student Julia Wang wrapped a drug-infused polymer sheath around the stent so that when it is stretched, it releases drug directly to the disease site.

“By changing the treatment method from a more passive release system to a more active release system, we are able to control when and how much drug is released,” says Wang.

“What is unique about this drug delivery system is that the amount of drug delivered depends on the extent the cloth is stretched. Using this approach a clinician can tune the dose, something they cannot do today,” says Grinstaff. “That control comes from the polymer composition and the engineering aspects of the design.”

Grinstaff and his team continue to refine the technology so it can pass through the regulatory process and get into the clinics. According to Grinstaff, his unique approaches to treating these diseases will not only lead to more effective treatment, but also will reduce the exposure of healthy cells to toxic chemotherapy drugs.

“Above all else, the potential benefit of both studies is the impact on patient care,” says Grinstaff. “By improving upon and streamlining the processes in place to treat aggressive diseases that currently have poor prognoses and no good therapies, not only are you going to treat the disease itself more effectively, but you will also improve the patient’s quality of life.”

Boston University College of Engineering

Originally Posted April 25, 2016

Appears on: BU ENG News Website, BU Research

From Cells to Circuits

~ saracody

Densmore leads BU team that collaborates with MIT in Science engineering biology study

Whether it’s artificial skin that mimics squid camouflage or an artificial leaf that produces solar energy, a common trend in engineering is to take a page out of biology to inspire design and function. However, an interdisciplinary team of Boston University researchers have flipped this idea, instead using computer engineering to inspire biology in a study published in Science in April 2016.

“When you think about it, cells are kind of computers themselves. They have to communicate with other cells and make decisions based on their environment,” says Douglas Densmore, associate professor of electrical and computer engineering and biomedical engineering, who oversaw the BU research team. “By turning them into circuits, we’ve figured out a way to make cells that respond the way we want them to respond. What we are looking at with this study is how to describe those circuits using a programming language and to transform that programming language into DNA that carries out that function.”

Using a programming language commonly used to design computer chips, electrical and computer engineering graduate student Prashant Vaidyanathan created design software that encodes logical operations and bio-sensors right into the DNA of Escherichia coli bacteria. Sensors can detect environmental conditions while logic gates allow the circuits to make decisions based on this information. These engineered cells can then act as mini processing elements, enabling the large-scale production of bio-materials or helping detect hazardous conditions in the environment. Former postdoctoral researcher Bryan Der facilitated the partnership between BU and the Massachusetts Institute of Technology to pursue this research study.

“Here at BU, we used our strength in computer-aided design for biology to actually design the software and MIT produced the DNA and embedded it into the bacterial DNA,” says Densmore. “Our collaboration is a result of sharing the same vision of standardizing synthetic biology to make it more accessible and efficient.”

Historically, building logic circuits in cells was both time-consuming and unreliable, so fast, correct results are a game changer for research scientists, who get new DNA sequences to test as soon as they hit the “run” button. This novel approach of using a common programming language opens up the technology to anyone, giving them the ability to program a sequence and generate a strand of DNA immediately.

“It used to be that only people with knowledge of computers could build a website, but then resources like WordPress came along that gave people a simple interface to build professional-looking websites. The code was hidden in the back end, but it was still there, powering the site,” says Densmore. “That’s exactly what we are doing here with our software. The genetic code is still there, it is just hidden in the back end and what people see is this simplified tool that is easy, effective, and produces immediate results that can be tested.”

According to Densmore, this study is an important first step that lays the foundation for future research on transforming cells into circuits, and the potential for impact is global, with applications in health care, ecology, agriculture, and beyond. Possible applications include bacteria that can be swallowed to aid in digestion of lactose to bacteria that can live on plant roots and produce insecticide if they sense the plant is under attack.

“The possibilities are endless, and I am excited about it because this is the crucial first step to reach that point where we can do those amazing things,” says Densmore. “We aren’t at that level yet, but this is a stake in the ground that shows us we can do this.”

The BU/MIT collaboration will continue underneath the Living Computing Project, which wasawarded a $10 million grant from the National Science Foundation in January 2016. Future studies will look to improve upon the circuits that were tested, add other computer elements like memory to the circuits, and expand into other organisms such as yeast, which will pave the way for implanting the technology into more complex organisms like plant and animal cells.

Boston University College of Engineering

Originally Posted April 13, 2016

Appears on: BU ENG News Website, BU Research

BU ENGineer Spring 2016 Magazine

~ saracody

I served as Managing Editor for Spring 2016 issue of ENGineer magazine.

Notable Writing Credits:

  • “Drone Home” Page 3-4
  • “Naturally Inspired” Page 10
  • “EPIC Dream Factory” Page 12-21
  • “Walsh Wins NASA Grant to Get a Wider View of Earth” Page 32

Bridging the Gap

~ saracody

Cells Build Bridges to Heal Damaged Tissue

The world can be a dangerous place. With more than 41 million visits to the emergency department due to trauma in the U.S. each year, it is crucial to study the process of wound healing and how medical intervention might facilitate it. A study led by Professor Christopher Chen (BME), published inNature Communications, points to a promising new direction researchers could use to better understand wound healing.

Chen and his research team have developed a three-dimensional microtissue culture that mimics the healing process more closely than the traditional two-dimensional culture of cells that researchers have long used.

“Healing wounds requires the human body to fill 3D spaces, so we reasoned that healing of wounded 3D microtissues would more closely resemble wound healing in the human body,” says Chen. “This finding has the potential to become the new standard to study wound healing in vitro.”

First, the research team bioengineered a unique cell culture system in which 3D microtissues are formed from wound repairing cells called fibroblasts embedded in a matrix of collagen fibers, similar to how they exist in the human body. Next, Selman Sakar from the Swiss Federal Institute of Technology in Lausanne and Jeroen Eyckmans, senior postdoctoral associate in Chen’s Tissue Microfabrication Lab, leading authors of this study, cut tiny holes in the microtissues and captured time-lapse videos of the reaction under a microscope. The images showed the fibroblast cells closing the gap and healing the tissue without any signs of scarring. The process of healing observed in these microtissues was surprisingly different from healing previously observed in cells cultured on traditional 2D surfaces.

“When we did the same molecular manipulations in a single-layer sheet of cells, key players that sped up healing in 3D actually slowed healing of the sheet,” says Eyckmans. “Also, the restoration of 3D tissue architecture that is absent in 2D but occurs in our microtissues is of high interest when thinking about how to induce tissue regeneration rather than scarring.”

Digging deeper, they looked at what might be happening with another scaffolding molecule called fibronectin, which plays a large role in wound healing. They found that the fibroblast cells were dismantling fibronectin present in microtissue and towing it in to the wound, using it to build a bridge to connect to the opposite side of the gap. The fibroblast cells flocked to the bridge and began producing their own fibronectin, completely filling in the wound until the defect returned to its three-dimensional form, completely restoring the wounded tissue.

“What was most surprising was that the cells didn’t just move in to close up the hole; they remodeled the entire matrix, modifying their environment to close the gap,” says Eyckmans. “This provides a new approach to studying wound healing and standardizing this practice in research could lead to many important insights in this field.”

While this technology would not be directly incorporated into patient care, future work could be done to develop this model into a research tool to explore a variety of questions, from scar formation to how the process could impact the speed of wound healing to the role various stresses play in the healing process.

Boston University College of Engineering

Originally Posted: March 25, 2016

Appears on: BU ENG News website

Drone Home

~ saracody

New Robotics Lab gives researchers and their ‘bots room to roam

As an animation technique, motion capture, has been prominently featured in a number of blockbuster films for more than a decade, bringing fictional characters, like Gollum from Lord of the Rings, to life. This same technology is allowing BU researchers study robotics and the relationship between man and machine in the new home of the Robotics Lab, located behind the Engineering Product Innovation Center (EPIC).

“The nicest thing about the facility is that we are now self-contained and everything is in one place,” says Professor Calin Belta (ME), director of the BU Robotics Lab, who moved his team into the shared space last semester and has been joined by the research groups of Professor John Baillieul (ME) and Assistant Professor Roberto Tron (ME). “Normally these types of workshop spaces are hidden away in basements, but the fact that we have such a large facility that is out in the open makes a huge difference in terms of atmosphere. It makes for a more collaborative environment, which makes the students happier.”

In addition to making the space student-friendly, the Robotics Lab has also had a positive impact among faculty as well, noted Ballieul.

“Faculty have embraced the facility as a shared resource,” says Baillieul. “This has led to a renewed sense of collegiality among the ME robotics research groups.”

The Robotics Lab includes an experimental arena, a workshop, a student seating area and a conference room. The experimental arena resembles a cross between a hockey arena and BattleBots ring. It consists of a motion capture system containing more than 50 infrared cameras and several short-throw projectors that can create dynamic images on the floor. Reflective balls on the robots allow researchers to track their movements with infrared as the robots perform various tasks in the arena.

“Most of my research is centered on mobile robotics,” says Belta, who uses the experimental arena frequently. “We are using both ground and aerial robots to develop control strategies for unmanned aircraft and ground vehicles in unstructured environments, such as disaster areas.”

By projecting images onto the floor in the experimental arena, Belta’s research team runs disaster relief scenarios, where the goal is to send a robot into a disaster zone and have it find its way through collapsed buildings and debris. They want it to be able to build a map, identify areas of interest and locate survivors. Not only do they want the robot to be able to gather data about disaster zones, they also want it to be self-aware in terms of knowing when it has to return to recharge.

The BU Robotics Lab is also home to a workshop, where lab members design and construct robots, an open-concept student workspace, and a sound-proof, wireless conference room that makes it easy to work with colleagues off-campus. Numerous whiteboards pepper the lab, with scribbled notes from brainstorming sessions attesting to the collaboration that takes place there.

Future plans for the facility include recruiting other groups to work in the space, while continuing to add equipment. Given the dynamic, visual nature of the lab and its research, Belta anticipates incorporating more outreach initiatives within its scope as well, such as the Technology Innovation Scholarship Program (TISP), which sends undergraduate engineering students into middle- and high-school classrooms to inspire the next generation of engineers. The Robotics Lab supplies smaller-scale robots that can be packed up and transported to classrooms and TISP students use them to give fun, interactive presentations about engineering and to work with students on designing and creating their own engineering projects.

“We are funded primarily by the Department of Defense, but we have received support from the National Science Foundation as well, which has a strong focus on outreach initiatives,” says Belta. “Recently there has been a big push to study robot-human interaction and maintaining this balance of giving the robot autonomy to make decisions and allowing the human to step in as needed. Our new facility allows us to experiment with this interaction in real-time, which is invaluable.”

Boston University College of Engineering

Originally Posted: February 29, 2016

Appears on: BU ENG News website, ENGineer Magazine Spring 2016