August 9, 2018

BME students identify global health needs by traveling to clinics in Brazil, China, India, and Uganda

For graduate students studying biodesign in the Department of Biomedical Engineering’s Center for Bioengineering Innovation and Design at Johns Hopkins University, the ultimate goal is to develop new medical technologies that will improve the lives of patients around the world. Each summer, these students form teams and travel abroad, working side by side with primary care providers in some of the world’s most underserved communities. Through immersion in the field, students experience firsthand the unique challenges associated with patient care in low-resource environments, allowing them to design solutions that overcome these barriers.

During their month abroad, CBID student teams observe hospital procedures, interview health care providers, and interact with local residents to understand the pressing clinical needs of the community. After returning to the Johns Hopkins Homewood campus in Baltimore, the teams spend the remainder of the school year designing, prototyping, and building solutions to the global health challenges they identify during their travels.

This summer, CBID students are:

  • studying infectious disease control in Brazil
  • examining the diagnosis and treatment of chronic obstructive pulmonary disease (COPD) in China
  • learning about ophthalmology and equitable eyecare in India
  • empowering mothers to identify neonatal illness in Uganda and Bangladesh

Read the teams’ blogs, linked above, to follow their journeys and discover what it takes to design the next generation of health care solutions.

August 6, 2018

A New Wave of BioTech Workers

The BioTechnical Institute of Maryland, Inc. (BTI) provides tuition-free training to high school graduates in Baltimore City. Johns Hopkins is one of the 25 organizations that provide hands-on experience for their interns, so they can go on to pursue careers in in-demand biotech jobs.

David Maestas, a Johns Hopkins University biomedical engineering Ph.D. student, has trained five BTI students in his lab, where he studies regenerative medicine.

He says mentoring interns through the BTI program allows him to give back to the community while getting extra help in his lab. “I came across BTI from an internet search. In the beginning, I thought that I was going to start from ground zero with training them, but I quickly realized these people are well-trained before they get here,” said Maestas.

That’s because they go through a nine-week program that combines classroom instruction and hands-on training in laboratory basics, such as how to grow and harvest cells, the basics of molecular biology, clean room gowning and properly disposing of biohazardous waste.

Margaret “Sue” Penno of the Johns Hopkins Genetic Resources biorepository and All Children’s Hospital biorepository founded BTI 20 years ago. Kathleen Weiss, executive director of BTI, says the institute has lifted economic and social barriers to meaningful careers for hundreds of Baltimore area residents. “We have people who come to us at a level of skill that needs upgrading and we are here to do that,” she says, “You learn best when you do and when you perform. You put on the goggles and lab coat. You are a professional.”

Students complete the program with a paid internship of up to 400 hours, which serves as a capstone, and Maestas says he is ready to take on more interns. “I can only spend so much time myself at the lab bench, organizing, labeling and running things on machines,” said Maestas. “Having the interns here to help has been a huge boost for our research.”

Weiss says the hope is that the internships lead to permanent employment. To date, about 375 program graduates have filled lab technician jobs in scores of universities, hospitals and life science companies. Johns Hopkins alone employs 25 percent of program alumni.

Weiss recalls one of her students who came to BTI homeless and living in emergency housing. After graduating from BTI, she accepted a lab position at an emerging local biotechnology company, all the while pursuing her bachelor’s degree and then a master’s degree. She is now working at a senior level for an international life sciences firm, has become a homeowner and is contemplating a Ph.D.

Maestas wants his Johns Hopkins colleagues to know that hiring a BTI intern is a win-win opportunity. “The interns are sincere, enthusiastic and dedicated to learning new things,” he said. “It provides experience and mentoring for people in the local community who you can trust with your experiments. What’s better than that?”

This article originally appeared on Johns Hopkins Medicine.

July 31, 2018

Johns Hopkins BME partners with world’s top engineering school

The Johns Hopkins University’s top-ranked Department of Biomedical Engineering has entered into an international partnership with the world’s No. 1 engineering school, Tsinghua University in Beijing, China, to give master’s level students the opportunity to earn graduate degrees from both institutions.

The Tsinghua JHU-BME Dual Degree MS program, finalized in May 2018, marks the first academic collaboration between Johns Hopkins BME, which boasts the nation’s top-ranked graduate programs, and Chinese powerhouse Tsinghua University, ranked by U.S. News & World Report as the world’s best global engineering school. The initiative will further enhance the research collaboration between the two institutions that started in 2008 with the establishment of a joint Center for Biomedical Engineering Research.

Over the two-year curriculum, students will study and conduct research in the United States and China, earning an MSE degree in biomedical engineering from Johns Hopkins and an MS degree from the Tsinghua Electronic Engineering or Biomedical Engineering departments.

“This partnership brings together the two best engineering programs in the world to position our students at the forefront of the rapidly expanding and dynamic medical technology innovation field,” says Michael I. Miller, the Bessie Darling Massey Professor and Director of Biomedical Engineering at Johns Hopkins. “The future of biomedical engineering education is global, and we are proud to partner with Tsinghua University to offer students this exciting opportunity.”

Tsinghua JHU-BME program students will spend their first year at Johns Hopkins University in Baltimore, Md., taking advanced, project-based courses in one of six BME focus areas that include biomedical data science, regenerative and immune engineering, neuroengineering, biomedical imaging and instrumentation, genomics and systems biology, and computational medicine. They will have the opportunity to work with top researchers, clinicians, and physicians at the Johns Hopkins School of Medicine and the Whiting School of Engineering.

During a second year, dual-degree MS students will travel to Tsinghua University in Beijing, where they will pursue a year of thesis research under the mentorship of China’s leading scientists and engineers. In China, students also will gain first-hand knowledge of the country’s rapidly growing medical technology industry and have the opportunity to participate in summer internships with leading Beijing companies and hospitals.

“This provides our students with the best of both worlds,” says Raimond L. Winslow, the Raj and Neera Singh Professor of Biomedical Engineering, director of the Institute for Computational Medicine, and the BME department’s vice chair of academic programs. “At Johns Hopkins, they receive specialized, hands-on training in emerging BME disciplines and access to one of the nation’s best medical schools. At Tsinghua, they gain a global perspective of research and product development that will make them an asset for future employers. Together, these experiences give them a competitive advantage in the global marketplace.”

Designed to foster international collaborations, students from Johns Hopkins will be joined by their counterparts from Tsinghua University. Program managers from both universities will support students enrolled in the dual degree MS program, providing personalized assistance with housing, transportation, course schedules, and other aspects of life in a new country.

More information about the Tsinghua JHU-BME Dual Degree MS Program can be found on the program webpage.

-Kristen Swaney

July 30, 2018

Meet the BME summer student researchers: Rachit Kumar

Each summer, approximately two dozen high school and undergraduate students join the Johns Hopkins Department of Biomedical Engineering for the opportunity to gain hands-on research experience under the mentorship of our pioneering faculty. Meet Rachit Kumar, one of five undergraduate students with hearing loss who will conduct research in Johns Hopkins auditory science and engineering labs this summer as part of the STEM-HEAR initiative spearheaded by Tilak Ratnanather, associate research professor of biomedical engineering. 

Name: Rachit Kumar
Hometown: Loveland, Ohio
School: Georgia Institute of Technology
Mentor: Tilak Ratnanather, associate research professor of biomedical engineering

Can you tell us about yourself?

I was born profoundly deaf in both ears, and received a cochlear implant in my right ear just before I turned two years old. My experience with a cochlear implant has led me to pursue a career that would allow me to give back to the communities that gave me a full life. I was very lucky to attend a good public school that continually encouraged my curiosity and desire to keep learning.

Why are you interested in pursuing research this summer?

“Research” is an incredibly broad term, and there are literally thousands of fields of research. My goal this summer is to narrow my research interests even more, especially in a way that would allow me to contribute significantly to multiple projects at one time. I also have the incredible opportunity to work with Dr. Tilak Ratnanather, a scientist whom I have admired for a long time because he is also hard-of-hearing and has met with great success in spite of—or more likely, because of—that challenge. 

Can you describe your research project?

I am currently working on finding and implementing traditional computer vision techniques to automate the denotation of layers of the brain from imaging and histological data. I am also exploring the idea of building and training a convolutional neural network to perform a similar task.

What do you hope to learn or gain from this experience?

I have already learned so much about the nature of working in a computational, or “dry,” lab, and this has given me a unique perspective on the differences in environment and expectations compared to a more typical bench, or “wet,” lab. I also hope to learn more about the nature of working on, writing about, and presenting computational research.

What are your plans for the future?

After graduating with my degree in biomedical engineering, I plan to apply to MD-PhD programs. I want to pursue an MD-PhD so that I can marry my clinical and research interests while also contributing to both of those communities, in part as a “thanks” for their enormous investment in me when I was younger. I was given the opportunity to hear, which helped me through my childhood.

How has your hearing loss affected your educational experiences?

I initially resented my hearing loss because of how limited I sometimes felt, but over time, I’ve come to appreciate the unique challenges it’s presented to me. Through these challenges, I was able to learn how to work around my limitations. I became better equipped to deal with difficulties, which helped me to challenge myself academically and to continually push my limits to try to improve myself.

How will your experience at Johns Hopkins this summer help you achieve your goals?

This experience will hopefully give me the opportunity to further define my interests and determine where I would like to go with my education. I also have the chance to work and collaborate with so many world-renowned professors, as well as like-minded students who are as motivated as I am to work for their future. I have also had the opportunity to learn many techniques in computational research that I will certainly be able to leverage as I move forward in my education, both at my home institution and beyond.

July 28, 2018

Meet the BME summer student researchers: Anne Rojona Feliciano

Each summer, approximately two dozen high school and undergraduate students join the Johns Hopkins Department of Biomedical Engineering for the opportunity to gain hands-on research experience under the mentorship of our pioneering faculty. Meet Anne Rojona Feliciano, one of five undergraduate students with hearing loss who will conduct research in Johns Hopkins auditory science and engineering labs this summer as part of the STEM-HEAR initiative spearheaded by Tilak Ratnanather, associate research professor of biomedical engineering.

Name: Anne Rojona Feliciano
Hometown: Manila, Philippines; raised in Dumont, New Jersey
School: University of Miami
Mentor: Amir Manbachi, lecturer of biomedical engineering

Can you tell us about yourself?

I am an optimistic person who is a firm believer in living in the moment and eating well. Outside of doing research and attending school, I enjoy trying different cuisines, going to new places, and dancing.

Why are you interested in pursuing research this summer?

I am interested in pursuing research this summer because I am currently on a master’s or PhD track, and I am applying to graduate schools this fall.

Can you describe your research project?

I am helping to develop a low-contact hearing screening tool that can be used in an open-air environment. We are currently developing an Android software application that functions as a tone generator, and acoustically validating its tones in an open-air environment.

What do you hope to learn or gain from this experience?

I hope that this research experience helps me narrow down my research interests, and gives me insight to what graduate school would be like.

What are your plans for the future?

My plans include working on auditory research in graduate school or working in the biotech industry. 

How has your hearing loss affected your educational experience?

Hearing loss has affected me as a student since the start of my academic career. I constantly have to look for ways for my school to accommodate me. In my experience, sometimes the hearing technology is outdated, useless, or inefficient, and private schools often do not accommodate people who are deaf/hard-of-hearing. Because hearing loss is a self-disclosed disability, hard-of-hearing students have to be strong advocates for themselves and for their disability.

How will your experience at Johns Hopkins this summer help you achieve your goals?

Not only has Johns Hopkins provided me with the necessary accommodations and a supportive environment, the university has also provided me with great mentorship. I would like to thank Dr. Tilak Ratnanather for being a great mentor and role model, and for always making sure I have the tools and resources I need. I would like to thank Ms. Cathy Will as well for putting together a summer internship program that has been an extremely valuable learning experience thus far.

July 27, 2018

STEM-HEAR: First cohort of students with hearing loss conducts summer research at Johns Hopkins

Prior to his second birthday, Rachit Kumar’s parents learned that he was deaf. A cochlear implant in the toddler’s right ear opened up a new and stimulating world. Still, as Kumar grew up, he often felt different from his hearing peers, and quickly developed strategies to cope with his hearing loss.

For instance, he arranged simple accommodations, such as sitting at the front of classrooms and printing out his notes before class. Kumar credits his current academic success to his problem-solving skills. “I learned early on in my life how to face challenges, and I also made sure to stay positive about learning even though the environment wasn’t always fun for me,” said Kumar. “I was fortunate to go to a public school where the teachers were extremely supportive, and they helped me stay motivated. Not all people with hearing loss have that kind of support.”

As a second-year biomedical engineering major at the Georgia Institute of Technology, Kumar developed a passion for computer science, math, engineering, and medicine. He is grateful to the medical and scientific communities for developing the cochlear implants that enabled him to hear, and wants to give back to these communities through his own clinical research in the future. With the hope of narrowing his research interests, he accepted a summer internship at the Johns Hopkins University working in the lab of Tilak Ratnanather, associate research professor of biomedical engineering.

Ratnanather, who himself has profound hearing loss, is on a mission to bring more deaf and hard-of-hearing students into science, technology, engineering, and math (STEM) fields. Since the early 2000s, he has been connecting with such students through the Alexander Graham Bell Association for the Deaf and Hard of Hearing, serving as a mentor to dozens of high school and undergraduate students from around the country. In 2015, then-President Barack Obama recognized Ratnanather’s efforts by awarding him the Presidential Award for Excellence in Science, Mathematics, and Engineering Mentoring (PAESMEM).

More recently, Ratnanather has partnered with the Johns Hopkins School of Medicine Summer Internship Program to provide students with hearing loss opportunities to gain advanced, hands-on experience in STEM disciplines. This year, he launched the STEM-HEAR initiative (STEM for students with Hearing loss to Engage in Auditory Research), forming a cohort of five college students, including Kumar, to conduct summer research in auditory science and engineering labs across the Johns Hopkins schools of Medicine and Engineering.

“When these students go to college, they may be the only ones there with hearing loss. It is quite common for them to experience anxiety related to what we call ‘imposter syndrome,’” said Ratnanather. “Students with cochlear implants sometimes struggle to truly be a part of the hearing world, but they really don’t feel like part of the deaf world either.”

Ratnanather says students with hearing loss must do three things to succeed in academia: they must recognize that support is available, understand what to do with that support, and find the motivation to keep going despite obstacles. The STEM-HEAR program was designed to provide students with important tools for career development, including mentorship, networking, and research experience.

“I consider myself lucky to have gone through these barriers when I was very young,” said Kumar. “There are certainly people who have to face them later in life and that can be challenging.”

This summer, Kumar is developing new methods to distinguish the different layers of cortex from one another in images of the brain. Different types of brain images, such as MRI scans, reveal unique features of the cortical layers, so Kumar is applying computational approaches to combine data from multiple image sources for a more detailed representation of the brain and its structures. By accurately segmenting the regions of the brain, Kumar and his colleagues hope to identify the structural differences associated with various neurological disorders, such as deafness, to improve the diagnosis and treatment of these conditions.

“It’s beneficial for these students to conduct research in the world of auditory science because it helps them understand their own hearing loss,” said Ratnanather. “It’s a multidisciplinary subject. They study the biological, mathematical, physical, engineering, and chemical aspects of hearing loss, and it’s the perfect entry point into STEM.”

In addition to their research, the summer interns participated in other SIP programming for career development, including the Johns Hopkins Career, Academic, and Research Experiences for Students (CARES) Summer Symposium, held July 26 at the School of Medicine campus. At the CARES symposium, Kumar and his fellow interns presented their poster on a project that they worked on together under Ratnanather’s guidance. Aspiring to make “mainstream” college more accessible to students with hearing loss, the interns developed ways of using automated captioning that would allow students to access new learning methods.

“Ultimately, I want deaf students to know that they do not need to go to special colleges,” said Ratnanather. “These students have every right to be exposed to the best professors out there.”

Ratnanather is planning to expand the STEM-HEAR initiative over the next several years with Amanda Brown, associate professor of neurology at Johns Hopkins. Supported by the National Institute of Health, the two will launch a new five-year program to mentor underrepresented minority students, including those with hearing loss, throughout the year and provide them with summer research opportunities. Ratnanather hopes to support six students with hearing loss starting next year, and plans to collaborate with colleagues at other institutions to establish similar programs nationwide.

Other students in the STEM-HEAR internship cohort include Yasmeen Alshabasy from Wesleyan University, Samuel Bidwell from Wesleyan University, Garrett Brown from the University of Florida, and Anne Rojona Feliciano from the University of Miami.

-Sarah Tarney

July 24, 2018

Meet the BME summer student researchers: Sam Bidwell

Each summer, approximately two dozen high school and undergraduate students join the Johns Hopkins Department of Biomedical Engineering for the opportunity to gain hands-on research experience under the mentorship of our pioneering faculty. Meet Sam Bidwell, one of five undergraduate students with hearing loss who will conduct research in Johns Hopkins auditory science and engineering labs this summer as part of the STEM-HEAR initiative spearheaded by Tilak Ratnanather, associate research professor of biomedical engineering.

Name: Sam Bidwell
Hometown: Bloomfield, CT
School: Wesleyan University
Mentor: Tilak Ratnanather, associate research professor of biomedical engineering

Can you tell us about what it was like growing up with hearing loss?

I was diagnosed with meningitis when I was about 11 months old. One of the side effects from the disease or the treatment was that the hair cells in my cochlea died, causing me to lose my hearing. My parents recognized very quickly that I was no longer getting enjoyment from my loud toys. I was given a hearing aid, but my hearing degenerated so quickly that it didn’t help, and I received a cochlear implant shortly after, within three months of losing my hearing. Now, I can hear almost as well as a person without hearing loss, but there have been times when my implants have made things more difficult, like when people don’t want to use the devices that will help me to hear them better. Still, that’s pretty rare.

How has your hearing loss affected your educational experiences?

I went to a small private elementary school that didn’t offer much support for deaf students. There were no hearing-impaired teachers, so there weren’t many people I could talk to if I had any issues. My parents took an active role early on in my education. My mom fought for my ability to get an education and has always been my best advocate. As I got older, I began advocating for myself. Even when I transferred to a public school that provided me with some additional resources, I relied on my own self-advocacy. I was always motivated by my interest in math rather than by my deafness. For me, it was something I had to overcome, not something I had to incorporate into everything.

How did you hear about the Johns Hopkins internship program?

Growing up, I volunteered with my local chapter of the Hearing Loss Association of America. The woman in charge suggested that I look into a particular summer camp run by the [Alexander Graham] Bell Association [for the Deaf and Hard of Hearing]. While I was in this program, one of the AG Bell financial officers introduced me to Tilak. We’ve had an on-and-off conversation going for a couple of years, and at one point, I mentioned that I was looking for an internship. Tilak was very generous and extended the opportunity for me to conduct summer research here at Hopkins.

Can you describe your research project?

My goal is to improve the segmentation of the six neural layers in the brain’s cortex, specifically in and around the Heschl’s gyrus, which contains the primary auditory cortex. Starting with the raw, three-dimensional image of the Heschl’s gyrus, I segment it manually, highlighting each cortical layer as a separate set of pixels. [Defining the cortical layers] is largely an unsolved problem because the starting images themselves can vary wildly in both quality and color, so a program that’s too fixed on a single type of image won’t produce a general solution. I’ve been working on automating a lot of my work because the human eye is not always reliable, and I’ve gotten to the point where I can do a very good automatic segmentation with minimal manual input. The whole point of the project is to improve the segmentation of the neural layers so that you can easily see the changes in the neural structure under various conditions, such as being deaf.

What do you hope to learn or gain from this experience?

Along with hands-on experience, this internship is helping me to understand potential applications for fields like mathematics and biomedical imaging. It’s interesting to see how subjects you wouldn’t normally associate with math can still involve a lot of math. I’m realizing that there are many more career options out there than I thought. As a math major, I don’t have to become an actuary or a math professor.

What are your plans for the future?

I know my future career will be heavily math related, and I’ve been thinking about becoming a math professor after I earn my PhD. There are some other alternatives I’m also considering. For example, maybe I’ll go for a physics professorship instead. Maybe I’ll go into astronomy. Maybe I’ll do something else. Whatever I do, it’s definitely going to involve a lot of mathematics, but I’ve got about 10 years to figure that out.

What advice do you have for other students with hearing loss?

I think it’s helpful to have role models who are deaf, but it’s also just as important, if not more so, to realize that you don’t have to let your deafness define you. You can define it. You can let it be your motivation, but it’s okay to be motivated by other things, too.

Just because people say you can’t or shouldn’t do something, doesn’t mean that you can’t or shouldn’t do it. For instance, I was told that I would never progress beyond a second-grade reading level, and now I’m a voracious reader. There are many things people will say we can’t do, but often times, it’s just because no one has ever bothered to try.

Getting a cochlear implant and going “mainstream” was the best choice for me. It may not be the best choice for others. There is no one-size-fits-all solution. Everyone will shape [his or her] own life experiences.

July 22, 2018

Eileen Haase receives Fulbright U.S. Scholar Award to Uganda

Eileen Haase, senior lecturer of biomedical engineering at Johns Hopkins University, has received a Fulbright U.S. Scholar Program award to Uganda. Haase will lecture at Mbarara University of Science and Technology as part of a project to strengthen the Ugandan school’s curriculum in biomedical engineering.

“By adapting proven Johns Hopkins teaching methodologies and academic programs, I will work with the faculty at Mbarara University of Science and Technology to design a new curriculum that prepares Ugandan students to be independent self-learners willing to tackle challenging problems,” said Haase. “The long-term goal is to build an internationally accredited biomedical engineering program in Uganda.”

Haase is one of over 800 U.S. citizens who will teach, conduct research, and provide expertise abroad for the 2018-2019 academic year through the Fulbright U.S. Scholar Program. Recipients of Fulbright awards are selected on the basis of academic and professional achievement, as well as record of service and demonstrated leadership in their respective fields.

Since its establishment in 1946 under legislation introduced by the late U.S. Senator J. William Fulbright of Arkansas, the Fulbright Program has supported more than 380,000 students, scholars, teachers, artists, and scientists. Designed to build lasting connections between the people of the United States and the people of other countries, the Fulbright Program operates in over 160 countries worldwide.

“I am excited to collaborate with faculty at Makerere University and Mbarara University to strengthen the existing relationship between Uganda’s biomedical engineering community and Johns Hopkins faculty,” said Haase. “My objective is to increase opportunities for Ugandan and Johns Hopkins students to work together on solutions to global health issues.”

With more than twenty-five years of teaching experience, Haase directs the undergraduate program in biomedical engineering at Johns Hopkins University. She has played an instrumental role in developing the department’s recently launched BME 2.0 undergraduate curriculum, which features hands-on, project-based courses in six cutting-edge biomedical engineering focus areas, such as biomedical data science, genomics and systems biology, and regenerative and immune engineering. She helped establish the BME department’s state-of-the-art Design Studio, a space for student innovation and design education, and has worked to promote STEM education for young girls through outreach programs with Baltimore elementary and middle schools.

July 20, 2018

Jordan Green selected for National Academy of Medicine’s Emerging Leaders program

Jordan Green, professor of biomedical engineering, was named one of the National Academy of Medicine’s Emerging Leaders in Health and Medicine. Together with the other 19 Emerging Leaders, he will collaborate with NAM members and other experts to shape the Academy’s priorities and advance knowledge and progress in science, medicine, policy, and health equity.

Selected by NAM leadership, participants in the Emerging Leaders program include early- to mid-career professionals from a wide range of health-related fields such as basic and translational science, clinical medicine, bioengineering, federal health policy and law, and ethics. Suchi Saria, John C. Malone Assistant Professor of Computer Science, will join Green in representing Johns Hopkins as a program participant.

“These exceptional individuals were selected to the National Academy of Medicine’s Emerging Leaders in Health and Medicine program for their leadership attributes and because they are poised to shape the future of health and medicine,” said NAM President Victor J. Dzau. “I look forward to engaging these impressive individuals, who are the next generation of scientists, health care providers, public health professionals, and policymakers, to develop a network of young leaders and catalyze innovative and cross-disciplinary activities addressing some of the most pressing challenges in health and medicine.”

Over a three-year term, program participants will engage in a variety of activities throughout the National Academies of Sciences, Engineering, and Medicine (National Academies), such as  planning the inaugural NAM Emerging Leaders Forum.  Scheduled for April 11-12, 2019, in Washington D.C., the forum will provide an opportunity for collaborative work and interdisciplinary discussions among the nation’s evolving leadership in health and medicine.

Additional Emerging Leaders program activities will include attending biannual meetings with NAM leadership; participating in National Academies convening activities, including standing committees, roundtables, workshop planning committees, and report review panels; publishing NAM Perspectives; and attending the NAM’s annual meeting each October.

Green is also a member of the Translational Tissue Engineering Center and the Institute for Nanobiotechnology at Johns Hopkins University. His research focuses on the design and development of biotechnologies and advanced therapeutics for drug and gene delivery.

-Sarah Tarney

July 12, 2018

Scientists create nano-size packets of genetic code aimed at brain cancer ‘seed’ cells

In a “proof of concept” study, scientists at Johns Hopkins Medicine say they have successfully delivered nano-size packets of genetic code called microRNAs to treat human brain tumors implanted in mice. The contents of the super-small containers were designed to target cancer stem cells, a kind of cellular “seed” that produces countless progeny and is a relentless barrier to ridding the brain of malignant cells.

Results of their experiments were published online June 21 in Nano Letters.

“Brain cancer is one of the most widely understood cancers in terms of its genetic makeup, but we have yet to develop a good treatment for it,” says John Laterra, M.D., Ph.D., professor of neurology, oncology and neuroscience at the Johns Hopkins University School of Medicine and a research scientist at the Kennedy Krieger Institute. “The resilience of cancer stem cells and the blood-brain barrier are major hurdles.”

Blood that enters the brain is filtered through a series of vessels that act as a protective barrier. But this blood-brain barrier blocks molecular medicines that have the potential to revolutionize brain cancer therapy by targeting cancer stem cells, says Laterra.

“To modernize brain tumor treatments, we need tools and methods that bypass the blood-brain barrier,” says Jordan Green, Ph.D., professor of biomedical engineering, ophthalmology, oncology, neurosurgery, materials science and engineering and chemical and biomolecular engineering at the Johns Hopkins University School of Medicine. “We need technology to safely and effectively deliver sensitive genetic medicines directly to tumors without damaging normal tissue.”

A case in point, Green says, is glioblastoma, the form of brain cancer that Arizona Sen. John McCain is battling, which often requires repeated surgeries. Doctors remove the brain tumor tissue that they can see, but the malignancy often returns quickly, says Laterra. Most patients with glioblastoma live less than two years after diagnosis.

Scientists have long suspected that cancer stem cells are at the root of what drives the return and spread of glioblastoma and other cancers. These stem cells give rise to other cancer cells and, if they evade the surgeon’s knife, can lead to an entirely new tumor.

Laterra and Green, who are members of the Johns Hopkins Kimmel Cancer Center, designed a way to efficiently deliver super-tiny packets of microRNAs into established brain tumors. The microRNAs target brain cancer stem cells to halt their capacity to propagate and sustain tumor growth.

The packets are made of biodegradable plastic similar to material used for surgical sutures and that degrades over time. They are 1,000 times smaller than the width of a human hair and typical of the size and shape of natural components that cells use to communicate. When cancer cells engulf the packets, they break apart and release their microRNA “payload” specifically where the microRNAs need to take action within the cancer cells.

Encased in the nanopacket are microRNAs that specifically bind to messenger RNAs linked to two genes: HMGA1 and DNMT, which function together to regulate gene expression programs in cells.

When microRNAs bind to these messenger RNAs, they block their protein-making abilities and turn off programs that drive the cancer cells’ stemlike characteristics. Without their stemlike properties, the cancer cells are more differentiated, they lose their capacity to propagate tumors, and they may be more susceptible to radiation and drugs.

For their experiments, the Johns Hopkins scientists implanted human glioblastoma cells into 18 mice. To mimic the clinical challenge of treating an existing tumor, the scientists waited 45 days before treating the animals to be sure they had well-formed tumors. Half of the animals received infusions of the nanopackets containing active microRNAs directly into their brain tumors, and the other half received nanopackets containing inactive microRNAs. To isolate the effect of the nanoparticles, the scientists used mice that were bred without immune system T-cells that target cancer cells.

Five of the nine mice receiving inactive microRNAs (controls) died within two months, and the rest of the control mice died within 90 days. Three of the nine mice receiving active microRNAs lasted up to 80 days, and six lived to 133 days. Those six were humanely euthanized, and isolated mouse brains were examined for the presence of tumors.

All of the control mice had large tumors in their brains when they died. Four of the mice that received active microRNAs and lived to 133 days had no tumors, and two had small ones.

Green says that many genetic medicines are designed to target one gene. The type of nanoparticles the Johns Hopkins team used in this study can encapsulate multiple types of microRNAs to target multiple gene networks.

When the brain cancer stem cells internalize the nanoparticle and transition to a non-stem-cell state, Laterra says, clinicians could exploit that condition, and give radiation or other drugs to kill the now-vulnerable cells.

Green says scientific teams elsewhere are developing microRNA packets using lipid-based materials, and some standard chemotherapy is delivered in a fatty nanoparticle called a liposome.

Green and Laterra say the nanoparticles in their study are able to permeate the entire tumor because rodent brains are small. Humans, with bigger brains, may need a pump and catheter to funnel nanoparticles throughout the brain.

The Johns Hopkins team is working to scale up development of its nanoparticles and standardize their stability and quality before applying for permission to begin clinical trials on people.

The research team has filed for a patent for part of the technology used in this research.

In addition to Laterra and Green, the cross-disciplinary team of scientists from Johns Hopkins who performed and contributed to this research includes Hernando Lopez-Bertoni, Kristen Kozielski, Yuan Rui, Bachchu Lal, Hannah Vaughan, David Wilson, Nicole Mihelson and Charles Eberhart.

Funding for the study was provided by the American Brain Tumor Association, the ARCS Foundation, the National Science Foundation, the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Research to Prevent Blindness and the National Institutes of Health (R01NS073611, R01EB016721, F31CA196163 and R01CA195503).