Ed Damiano has devoted more than decade to developing a bionic pancreas
By Joel Brown, BU Today
Two million people in the US live with potentially deadly type 1 diabetes, and Ed Damiano wants to make them healthier, safer, and “dramatically unburdened from managing their diabetes.”
Among those people is his son.
Damiano was honored on July 12 as Boston University’s 2016 Innovator of the Year for his efforts developing an artificial, or bionic, pancreas that regulates blood sugar levels by automatically delivering precisely calibrated doses of insulin or glucagon every five minutes.
“People will be healthier on this device from the very first day they put it on,” says Damiano, a College of Engineering professor of biomedical engineering.
The Innovator of the Year award, presented by the Office of Technology Development, recognizes a BU faculty member whose cutting-edge research is being brought to market and benefits society at large.
The wearable device will be the subject of a small National Institutes of Health-funded human clinical trial, called a bridging study, at four US sites this winter, in preparation for the Phase III or pivotal trial, which will generate data for FDA evaluation of the device. That trial will begin enrollment in the first half of 2017 and involve more than 600 patients at 16 clinical centers around the country.
Damiano’s special reason for undertaking the project, his son David, was diagnosed with type 1 diabetes when he was 11 months old. That’s terrifying news for any parent, and Damiano took it as a challenge. While he will just miss his long-term goal—getting the bionic pancreas to market before his now 17-year-old son goes off to college in fall 2017, he is pleased with his progress.
“Ed’s determination and his systematic and persistent work to achieve this goal has been incredibly impressive,” says Gloria Waters, vice president and associate provost for research, who presented the award. “He has worked tirelessly, and his success in raising funds from a wide range of sources, carrying out the science, and developing the technology in a very short period of time has been nothing but remarkable.”
Damiano with Gloria Waters, vice president and associate provost for research, as she presents him with the 2016 Innovator of the Year Award at the University’s Tech, Drugs, and Rock n’ Roll event.
Damiano’s device is called the iLet, a reference to the pancreatic islets of Langerhans, the hormone-producing areas of tissue in a healthy pancreas. It looks like a thick iPhone, with two ports on the end for the tiny drug delivery tubes. A subcutaneous sensor provides the blood sugar data to the device via Bluetooth.
The device’s firmware contains algorithms that automatically adjust drug dosing every five minutes. That’s a great improvement over the current system, which requires the user to do frequent blood testing and calculations, then inject insulin or consume food to correct their levels. And because the device is bi-hormonal, delivering both insulin (to lower blood sugar) and glucagon (to raise it), the ups and downs of a user’s blood sugar levels can be kept in a much narrower and safer range.
The iLet will be studied with insulin only first, and then in the bi-hormonal mode. Assuming everything goes smoothly, the insulin-only device could come to market in 2018 and the bi-hormonal version in 2019.
While Damiano says he’s honored at being named Innovator of the Year, he’s not taking time out to celebrate.
“Being ebullient and enthusiastic about all the accomplishments that have come so far is great, but it’s a distraction,” Damiano says. “The enthusiasm I have for that reality is masked by the immense amount of work to do over the next 24 months.”
That work includes everything from a variety of subsidiary approvals to manufacturing hurdles to financial matters. As the device is approved, Damiano also has to persuade health care payers to approve it for patients. “I have great confidence that they will reimburse it, but it’s not a passive process,” he says. “I have to get in front of all these payers and show them how far superior this technology is to the standard of care. I think at that point the data will convey the message all by itself.”
The Innovator award also recognizes entrepreneurial efforts, in this case Damiano’s creation of a new medical technology company called Beta Bionics with several partners, including his longtime collaborator Firas El-Khatib, a BU senior research scientist. In 2014-15, before starting Beta Bionics, Damiano raised about $2.5 million in donations to his lab at BU from the diabetes community. At the end of 2015, Eli Lilly and Company invested $5 million in Beta Bionics, which is also building equity by crowdfunding, at $100 a share, via a Wefunder page, with about $900,000 raised from 650 investors.
“It’s unusual for someone to take something this far from the genesis of the concept. Usually we hand it off,” says Michael Pratt (Questrom’13), interim managing director of the Office of Technology Development, who volunteered as a healthy control subject in one of Damiano’s early studies and remains deeply impressed by his commitment.
“Ed was maniacal about caring for his son, setting his alarm to get up every hour through the night and check his blood glucose. I can’t imagine what that was like,” Pratt says. “Then he sat down with Firas in Bertucci’s in Kenmore Square, and they had this back and forth till they came up with the kernel of the algorithm mimicking how Ed cared for his son. That kernel persists to this day. He means business. He’s seeing this through.”
Beta Bionics is a public benefit corporation, a for-profit corporate model that allows for socially responsible decision making, such as choosing to decline a profitable buyout offer to keep the bionic pancreas on track for fast development and wide distribution.
“The company becomes a vehicle for the movement he’s creating here,” Pratt says, “but not in the traditional sense of going out there and trying make a million dollars. He’s trying to rally people together to treat this disease.”
This story originally appeared on BU Today.
A current Boston University BME PhD student and a BME undergraduate alumna both placed at the recent Summer Biomechanics, Bioengineering, and Biotransport Conference (www.sb3c.org) in National Harbor, Maryland.
Current Boston University BME PhD student, Lauren Mangano, placed 3rd in the category of “Signaling and Remodeling”. Mangano is a current member of the Morgan Lab within the Boston University College of Engineering.
Boston University BME alumna, Chantal De Bakker (BS BME 2012), won 2nd place in the same category of “Signaling and Remodeling”. De Bakker is currently enrolled in the BME PhD program at The University of Pennsylvania.
Out of the 124 submissions, 36 finalists (six finalists in each of six scientific categories) were selected. Each finalist gave a 12-minute conference presentation followed by a Q&A period. For each category, 1st, 2nd, and 3rd place were awarded.
BME Assistant Professor Darren Roblyer has been awarded a St. Baldrick’s Research Grant for his work on childhood osteosarcoma. For more details on the St. Baldrick’s Foundation, please visit http://www.stbaldricks.org/
Work by the Zaman Lab has been featured on the cover of Biophysical Journal. The article”A Computational Model of YAP/TAZ Mechanosensing” by Meng Sun, Fabian Spill, and BME Professor Muhammad Zaman has also been published in the June 6, 2016 issue.
Commencement Ceremonies Celebrate the Class of 2016
By Sara Elizabeth Cody
Sunshine from the warm, cloudless day penetrated the air of excitement inside the Track and Tennis Center, where faculty, staff, family and friends gathered to celebrate the 63rd commencement of 350 undergraduate students from the College of Engineering on May 14.
Dean Kenneth Lutchen began the ceremony by acknowledging the challenges students had to face and overcome in order to arrive at that moment today, noting that while engineering is the toughest course of study at BU, “the hard is what makes it great, and you made it.”
Lutchen also recognized the important role that family and friends played in supporting their graduates, noting that commencement was a celebration that was years in the making.
“From first steps to learning you were admitted into this great institution, you have been celebrating achievements and important milestones for the past 22 years,” he said. “Today you will celebrate the best investment you could have made walking across this stage.”
Student speaker Alexander James O’Donovan (BME’15) spoke about his personal experience of being diagnosed with Type 1 diabetes and how it drove him to pursue his career in biomedical engineering and ultimately landed his dream job working in Professor Ed Damiano’s (BME) laboratory developing the bionic pancreas. From the beginning, he identified closely with the College’s vision of creating Societal Engineers and that allowed him to carve out a path for his success.
“I came here because I wanted to change the world and [the College] wanted to create people to change the world,” said O’Donovan. “We now have what we need to leave our footprint on the world—the only question now is how big the footprint will be.”
U.S. Secretary of Energy Ernest Moniz (Hon.’16) took the stage after O’Donovan to deliver his keynote address. After a lighthearted moment where he explained he wore his beaver print tie because beavers are “nature’s engineer,” he stressed the importance of how engineers help move society forward by describing the four pillars of engineering: to solve problems; to think broadly in order to find novel solutions; to be civic-minded; and to think globally to have a lasting impact on the world. Echoing O’Donovan�s sentiments about the Societal Engineer, he noted how BU’s vision brings these pillars together.
“As an engineer, you have both an obligation and an opportunity to improve the lives of the underserved, both in this country and across the world,” said Moniz. “It is the highest form of diplomacy.”
Moniz—who received an honorary Doctor of Laws degree at the university-wide commencement ceremony the next day—also noted that the newest generation of engineers must pick up the mantle to continue tackling some of society’s greatest challenges, from political discourse to climate change, by harnessing their education and skills acquired during their time at BU.
“I personally believe that the engineering profession is one that is associated with social progress,” said Moniz. “No matter what you decide to do with your engineering degree, your ‘science-based approach with a system-wide view’ to solve problems will present new opportunities for solutions.”
Lutchen presented Department Awards for Teaching Excellence to Professor Hamid Nawab (ECE), Associate Professor of Practice William Hauser (ME) and to Assistant Professor Ahmad Khalil (BME), who also received Outstanding Professor of the Year Award. The Faculty Service Award went to professor Irving Bigio (BME).
Later in the afternoon, Dean Lutchen presented 200 Master’s degrees and presided over the hooding of 48 PhD students in the Fitness and Recreation Center.
Alfred O. Hero (EE’80), R. Jamison and Betty Williams Professor of Engineering at University of Michigan, Ann Arbor and co-director of the Michigan Institute for Data Science gave the graduate convocation keynote address. As a BU alum, he remembered sitting in the same place as this year’s graduates 36 years ago. He encouraged graduates never to succumb to challenges, to defend their work, and to remain humble and kind throughout their future careers.
“Engineering has given you the skills to organize and navigate through complex data and use it to solve problems,” Hero concluded. “In my experience, the two most prominent characteristics of successful engineers is the pursuit of unconventional ideas and the perseverance to get it done.”
By Sara Elizabeth Cody
When it comes to treating cancer, one BU researcher is going local. Professor Mark Grinstaff (BME, MSE, Chemistry, MED) recently published two studies 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. “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 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.”
By Sara Elizabeth Cody
On Thursday, April 14, Professor M. Selim Ünlü (ECE, BME, MSE), recipient of the 2016 Charles DeLisi Award and Distinguished Lecture, presented “Optical Interference: From Soap Bubbles to Digital Detection of Viral Pathogens” to a packed room of students, faculty and researchers.
The first named endowed lecture in the history of the College of Engineering, the Charles DeLisi Award and Distinguished Lecture recognizes faculty members with extraordinary records of well-cited scholarship, and outstanding alumni who have invented and mentored transformative technologies that impact our quality of life.
When Ünlü arrived at BU in 1992, he was inspired by the collegial interdisciplinary environment, which led him to apply his background in electrical engineering and electromagnetic waves to developing innovative methods for biological imaging and sensing. His presentation, peppered with video and audio messages from past students and mentors who have contributed to his work, chronicled his career path from graduate school to present day and centered on his current research in optical sensing and developing new bioimaging technologies that address the obstacles that currently plague the field of diagnostics.
“When you are trying to look at pathogens, the most distinguishing thing is to look at its genome, but obstacles like logistics and cost are prohibitive and drive scientists to find more compact and affordable ways that have the same functionality,” said Ünlü. “Single particle detection has been the physicist’s dream of addressing these issues, so that’s what we set out to explore.”
Synergy between Engineering and Medicine
In developing his optical detection technology, he drew inspiration from, of all places, a soap bubble. Specifically, the patterns of colors that develop on the surface when light is being reflected through it. According to Ünlü, the same interference phenomenon that gives rainbow colors to soap bubbles can also provide extremely high sensitivity as illustrated by the recent news on detection of gravity waves by optical interferometry.
“Most people don’t realize that just by calling out a certain color, you are making a measurement in the order of nanometers,” said Ünlü.
Ünlü extended this idea to develop his optical detection technology for single nanoscale particles, where the interference of light reflected from the sensor surface is modified by the presence of nanoparticles, producing a distinct signal that reveals the size of the particle that is otherwise not visible under a conventional microscope. Using this technology, Ünlü and his research team demonstrated label-free identification of some of the most deadly viruses in the world, including hemorrhagic viruses like Ebola, Lassa and Marburg, at a high sensitivity on par with state-of-the-art laboratory technologies. They have even been able to detect particles as small as individual protein and DNA molecules by labeling them with gold nanoparticles to provide sufficient visibility.
“Proteins are too small. We can’t see them directly so we decorate them with gold nanoparticles, which are not much bigger than the proteins themselves,” said Ünlü. “Decorating them with gold nanoparticles increases visibility of the molecules bound on the sensor surface, and we are able to count them in serum or whole blood.”
The resulting technological development in biomarker analysis that Ünlü has spearheaded is digital detection, an approach that counts single molecules, which provides resolution and sensitivity beyond the reach of ensemble measurements. Digital detection for medical diagnostics not only provides very high sensitivity, but also has the potential of making the most advanced molecular diagnostic tools broadly accessible at low cost.
Digital detection captures images of individual viruses in real time
“Optical interference is a very powerful sensing technique,” summed up Ünlü. “With this biological imaging technology, we can detect single particles if they are large enough on the nanoscale, such as viruses, and see them directly. If they are proteins or DNA molecules we have to label them with a small, metallic nanoparticle to see them.”
In terms of next steps, Ünlü and his team will continue to refine the technology for commercialization, including applying some of these findings to produce microarray chips that provide calibration and quality control in industry. His laboratory will continue to work on advancing the technology further and gaining a deeper understanding of the theoretical basis in order to enhance the methodology. In particular, they are looking into applying the technology to such areas as real-time DNA detection, rare mutations, and most recently a project to characterize viruses that target cancer cells.
To conclude his presentation, Ünlü expressed his appreciation of the support he received from the College to foster collaboration, and to his students, mentors and family who helped him along the way.
“I’m very thankful to Boston University for providing an incredibly rich environment for research because there are no barriers between disciplines,” said Ünlü. “Multidisciplinary innovation is the driving force of discovering new things and making society better, and ultimately that is my motivation.”
The DeLisi Lecture continues the College’s annual Distinguished Lecture Series, initiated in 2008, which has honored several senior faculty members. The previous recipients are Professors John Baillieul, (ME,SE), Malvin Teich (ECE) (Emeritus), Irving Bigio (BME), Theodore Moustakas (ECE, MSE), H. Steven Colburn (BME), Thomas Bifano (ME, MSE), Christos Cassandras (ECE, SE) and Mark Grinstaff (BME, MSE, Chemistry, MED).
Transforming Living Cells into Computers
By Sara Elizabeth Cody
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 BU researchers have flipped this idea, instead using computer engineering to inspire biology in a study recently published in Science.
“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 Associate Professor Douglas Densmore (ECE, BME), 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, ECE 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 healthcare, 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 was recently awarded a $10M grant from the National Science Foundation. 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.
Biomedical Engineering Assistant Professor Ahmad Khalil has been awarded the 2015 Hartwell Individual Biomedical Research Award for his research “Detecting Antibiotic Resistance with RNA Sensors”.
More information about the Hartwell Foundation can be found through their website: http://www.thehartwellfoundation.com/index.shtml
Cells Build Bridges to Heal Damaged Tissue
By Sara Elizabeth Cody
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.”
3D Microtissue Wound Healing
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.