Students organize efforts to 3-D print PPE for the Johns Hopkins Hospital
While most of his classmates were preparing for final exams and upcoming summer internships, Chris Shallal spent the end of his third year focused on a multi-campus effort to create and provide durable, reusable face shields to healthcare workers at the Johns Hopkins Hospital.
To help fill the hospital’s urgent need for personal protective equipment (PPE) due to the COVID-19 pandemic, the Johns Hopkins Consolidated Service Center (CSC) recruited volunteers to assemble disposable foam face shields. Shallal, a third-year biomedical engineering student, noted that the foam headbands used for these face shields do not hold up to prolonged wear, and must be disposed after a single use because the porous material could potentially trap hazardous particles. He and his fellow engineering classmates at Health 3D, a social venture that uses 3-D printing to improve healthcare products, submitted a proposal to the Johns Hopkins COVID-19 Research Response Program detailing their plan to manufacture a more durable headband that would allow face shields to be worn multiple times.
With the help of Elizabeth Logsdon, senior lecturer of biomedical engineering, and Warren Grayson, associate professor of biomedical engineering, the team’s proposal was accepted, and they were provided $10,000 to use toward printing materials. To make the headbands, the team is using extra-tough PETG filament, known for its strength and stability. It can be wiped down with basic cleaning agents such as isopropanol, bleach, or ethanol without affecting its durability.
Working with the Johns Hopkins COVID-19 Command Center, Shallal built a network of approximately 30 people and more than 55 3-D printers to create the reusable headbands using a printing design created by the Johns Hopkins Applied Physics Laboratory. Once printed, the headbands are dropped off at designated checkpoints and delivered to the Central Supply Chain warehouse, where a transparent shield and elastic band are attached to complete the new, more durable face shields, which are distributed into the hospital system.
“Setting up the network included onboarding new members and providing the appropriate 3-D printing feedback to ensure they could get the shields into production,” said Shallal. “Our goal is to provide 8,000 reusable shields to the Johns Hopkins Hospital network within two months.”
3-D printing is adaptable and can be rapidly deployed, mainly because it does not require a large upfront cost like other industrial manufacturing methods, Shallal said. Once all non-essential in-person activities were cancelled, Shallal and his teammates realized that many of the university’s 3-D printers were suddenly inactive and available for the COVID-19 response.
“This student-led team has exceeded expectations in their organization and execution of this project. We are so impressed with their passion to provide support for our Hopkins medical community, all while completing their spring semester coursework. They are an inspiration to their peers, staff, and faculty,” said Logsdon.
Shallal and his team are looking to increase production by recruiting more members and activating more printers. They are also considering other manufacturing methods, like vacuum forming or industrial casting and molding.
If you have access to 3-D printers and would like to participate in this initiative, please fill out this form to get started.
May 20, 2020
Meet Scott Wilson, assistant professor of BME
Scott Wilson joined the Johns Hopkins Department of Biomedical Engineering as an assistant professor in January 2020. In this interview, he discusses his research in biomaterials and immunoengineering, a memorable “eureka” moment, and his goals for the future.
What made you pursue a career in biomedical engineering?
While I was a chemical engineering undergraduate student, over a three-year span, my father was diagnosed with a string of debilitating diseases. During this time, I could only standby dismayed and frustrated as I watched my father suffer from the effects of these ailments. It was then that I decided to dedicate my life to making people’s lives, and not the things we buy, better.
Why did you choose Johns Hopkins BME? What are you looking forward to most?
I chose to join Johns Hopkins BME because of the unmatched quality of the students, and the opportunity to work with collaborators at JHU, both within and outside the BME department, who are leaders in their fields of expertise and dedicated to engineering the future of medicine.
Can you give a brief overview of your current research?
My lab’s research focuses on the synthesis and preclinical validation of biomaterials-based immunomodulatory therapies that bias the adaptive immune response towards antigen-specific immunity or tolerance. Utilizing organic chemistry, the aim of my group is to synthesize bespoke biomaterials with specific immunomodulatory functionalities. In particular, we are interested in the development of immunity-inducing therapies for the treatment of cancer and infectious disease, as well as tolerance-induction strategies that knock out the antigen-specific immune responses that drive autoimmunity, transplant rejections, and the immunogenicity of protein-based therapeutics.
Have you ever experienced a “eureka moment?”
Before I started my PhD, I was very nervous about joining a lab that focused on biomaterials synthesis. I had not excelled in my Organic Chemistry courses as an undergrad, and I had hoped that the reactions I had done in my Organic Chemistry II Lab were my last. After several months of toil in the lab, I was finally able to complete the synthesis of a novel polymer. I showed the purified material to a postdoc in the lab and started asking her to speculate about the properties of the material. After suffering a few of my naïve questions, she said with a laugh, “This material has never existed before. We will have to test it to answer all these questions.” It was then that I realized that the only place in the world this material could be found was in the vial in my hand. I then fully appreciated and fell in love with the power of organic chemistry, and the ability to synthesize truly unique materials with unprecedented functionalities.
What do you consider your biggest research accomplishment so far?
During my postdoc in Professor Jeffrey Hubbell’s lab, I had the opportunity to pioneer the development of a biomaterials-based strategy to specifically knock out the activity of the auto-reactive T cells that drive autoimmunity (see paper). Based on the efficacy of this biomaterials-based strategy in pre-clinical animal models of autoimmunity, this technology has been transitioned to the clinic and is being investigated in a Phase 1 clinical trial for the treatment of celiac disease. I am extremely excited to have the opportunity to translate one of our therapies into the clinic, and I’m very grateful to the patients who have volunteered for the study.
What impact would you like your work to have?
I would like my work to have two major impacts. The first is to deliver clinically-viable therapies that cure and prevent disease. The second is to provide a unique learning environment that prepares students and trainees to maximize their potential and achieve their long-term life goals.
What are your goals for the future?
My goal is to establish a lab that is recognized as a leader in the development of biomaterials and immunomodulatory therapies. I’m also striving to create a lab that provides a positive training experience, and produces a cadre of young scientists that are able to go forth into the world and have a positive impact on human health. Finally, I wish to contribute to the educational experience of undergraduate and graduate students by establishing courses in immunoengineering and biomaterials that are both fun and challenging.
Do you have any career advice to offer to current students?
Take setbacks as opportunities to learn and improve. When something does not go your way, even if others are more at fault, always question if there was something you could have done better. Focusing on self-improvement will lead to a better version of yourself, and keep you from getting caught in the unproductive trap of worrying about things that are out of your control.
What do you enjoy doing outside the lab?
I enjoy doing activities that allow me to interact with nature, such as hiking, biking, swimming, etc. I also have a passion for travel. To me, there is nothing more rewarding than learning about the history and culture of places abroad and close to home. It allows us to be more empathetic, and provides a mirror for us to reflect on our own way of being.
Johns Hopkins team develops new method to make kidney dialysis fluid for patients with COVID-19
The ongoing COVID-19 pandemic has severely impacted the manufacturing and supply chains for many products. But while shortages of toilet paper, disinfectant cleaners, and hand sanitizer get most of the news coverage, the diminishing reserve of one item — kidney dialysis fluid, also known as dialysate — presents a grave threat to the lives of people with acute kidney injury (AKI), including the approximately 3% to 9% of COVID-19 patients who develop the disorder.
Without the special type of 24-hour, slowly administered dialysis — called continuous veno-venous hemodialysis, or CVVHD — that is given to AKI patients in an intensive care unit, damaged kidneys cannot remove wastes and excess fluids from the blood as they normally do. Unfortunately, the COVID-19 pandemic has severely tapped dialysate supplies across the nation.
When two New York-based hospitals recently contacted Derek Fine, clinical director of nephrology at the Johns Hopkins University School of Medicine, to seek spare dialysate to help meet their need for some 3,000 liters per day (for all of their AKI patients in ICUs, both with and without COVID-19), he and Chirag Parikh, director of the medical school’s Division of Nephrology, came up with a better idea to remedy the problem.
Their solution was to replace the dwindling stocks of pre-mixed, commercially produced dialysate required for short-term ICU kidney dialysis machines with a suitable substitute manufactured by conventional hemodialysis devices and designed for long-term treatment.
The latter creates its own dialysate in real time from ultrapure water and concentrated chemical solutions.
Fine, Parikh, and colleagues from their division studied the workings of a conventional dialysis machine, learned how it manufactures dialysate and then adjusted the system to override alarms, which if triggered would automatically shut down dialysate production. However, one major obstacle remained: how to get the newly minted dialysate into bags.
“When we tried it out, we were successfully able to capture the dialysate, and that was the eureka moment,” Parikh says.
The U.S. Food and Drug Administration has already provided guidelines for the method, calling for all dialysate produced to be tested intermittently for bacteria and used within 12 hours from its origin. The two New York hospitals that spurred the birth of the new technique are reporting that it has enabled them to maintain sufficient supplies of dialysate for CVVHD.
May 19, 2020
Researchers urge clinical trial of blood pressure drug to prevent lethal complication of COVID-19
Researchers in the Ludwig Center at the Johns Hopkins Kimmel Cancer Center report they have identified a drug treatment that could—if given early enough—potentially reduce the risk of death from the most serious complication of Coronavirus disease 2019 (COVID-19), also known as SARS-CoV-2 infection.
Prazosin, a U.S. Food and Drug Administration-approved alpha blocker that relaxes blood vessels, may specifically target an extreme inflammatory process often referred to as cytokine storm syndrome (CSS) that disproportionately affects older adults with underlying health conditions, and is associated with disease severity and increased risk of death in COVID-19 infection. Using it pre-emptively to address COVID-19-associated hyperinflammation of the lungs and other organs has the potential to reduce deaths in the most vulnerable populations, they say.
In a report of their findings published April 30 in the Journal of Clinical Investigation, the researchers caution that although they believe if given early enough after viral exposure, the drug could prevent some deaths, it would not work in patients with advanced stages of the disease. They also emphasize that controlled clinical trials for this novel use of prazosin are needed before it can be safely recommended.
The investigators published the letter, they said, in hopes of stimulating rapid efforts to conduct such trials.
In the letter, the researchers described how they have been working in collaboration with researchers in the Johns Hopkins Divisions of Rheumatology and Infectious Diseases, and Departments of Neurology and Neurosurgery, to identify chemical ways of safely blocking the actions of catecholamines and cytokine responses. Together, catecholamines and cytokines enhance the inflammatory process that leads to severe COVID-19 symptoms, explains Chetan Bettegowda, M.D., Ph.D., Jennison and Novak Families Professor of Neurosurgery, who is senior author of the paper.
“The purpose of our article is to make the biomedical community aware of the potential of this approach and to stimulate additional basic and clinical research. Although, we are excited about this idea, we stress that a clinical trial is necessary to know if this intervention will help COVID patients, and that is where we are focusing all of our attention,” says Bettegowda.
In mouse models of CSS, they found that prazosin—commonly used to treat blood pressure, prostate gland enlargement and other conditions—blocked catecholamines (hormones released by the adrenal glands when the body is under stress), reduced cytokine levels, and increased survival after exposure to agents that trigger cytokine storm responses similar to those observed in COVID-19.
Prazosin is taken by mouth, costs less than $25 per month in the United States, and has been safely taken by millions of people over the last two decades. This should enable highly expedited clinical trials in people early after exposure to the SARS-CoV-2 virus, say the researchers.
“All drugs can have unanticipated side effects when used in new situations, so it is critical to evaluate the effectiveness and side effects of this drug in controlled clinical trials before it can be safely recommended for public use. This is particularly important for drugs like prazosin, which are already sold in pharmacies,” says Bettegowda.
Maximilian Konig, M.D., research fellow and lead author of the report, says a vaccine remains the best long-term hope to prevent deaths from COVID-19 but notes, at present, there are hundreds of individuals throughout the world who are dying every day. “Prazosin is already widely available, known to be safe and inexpensive, and the regulatory path for use in individuals exposed to the virus is straightforward,” he says.
The CSS treatment was granted Food and Drug Administration approval to be studied in a clinical trial for individuals with COVID-19.
In addition to Bettegowda and Konig, other researchers include Michael Powell, Verena Staedtke, Ren-Yuan Bai, David Thomas, Nicole Fischer, Sakibul Huq, Adham Khalafallah, Allison Koenecke, Ruoxuan Xiong, Brett Mensh, Nickolas Papadopoulos, Kenneth Kinzler, Bert Vogelstein, Joshua Vogelstein, Susan Athey, and Shibin Zhou.
In 2017, Johns Hopkins University filed a patent application on the use of various drugs to prevent cytokine release syndromes, on which Verena Staedtke, Ren-Yuan Bai, Bert Vogelstein, Kenneth Kinzler, and Shibin Zhou are listed as inventors.
May 18, 2020
Johns Hopkins researchers to use machine learning to predict heart damage in COVID-19 victims
Johns Hopkins researchers recently received a $195,000 Rapid Response Research grant from the National Science Foundation to, using machine learning, identify which COVID-19 patients are at risk of adverse cardiac events such as heart failure, sustained abnormal heartbeats, heart attacks, cardiogenic shock and death.
Increasing evidence of COVID-19’s negative impacts on the cardiovascular system highlights a great need for identifying COVID-19 patients at risk for heart problems, the researchers say. However, no such predictive capabilities currently exist.
“This project will provide clinicians with early warning signs and ensure that resources are allocated to patients with the greatest need,” says Natalia Trayanova, the Murray B. Sachs Professor in the Department of Biomedical Engineering at The Johns Hopkins University Schools of Engineering and Medicine and the project’s principal investigator.
The first phase of the one-year project, which just received IRB approval for Suburban Hospital and Sibley Memorial Hospital within the Johns Hopkins Health System (JHHS), will collect the following data from more than 300 COVID-19 patients admitted to JHHS: ECG, cardiac-specific laboratory tests, continuously-obtained vital signs like heart rate and oxygen saturation, and imaging data such as CT scans and echocardiography. This data will be used to train the algorithm.
The researchers will then test the algorithm with data from COVID-19 patients with heart injury at JHHS, other nearby hospitals and perhaps some in New York City. The hope is to create a predictive risk score that can determine up to 24 hours ahead of time which patients are at risk of developing adverse cardiac events.
For new patients, the model will perform a baseline prediction that is updated each time new health data becomes available.
As far as the researchers are aware, their approach will be the first to predict COVID-19-related cardiovascular outcomes.
“As a clinician, major knowledge gaps exist in the ideal approach to risk stratify COVID-19 patients for new heart problems that are common and may be life-threatening. These patients have varying clinical presentations and a very unpredictable hospital course,” says Allison G. Hays, Associate Professor of Medicine in the Johns Hopkins University School of Medicine’s Division of Cardiology and the project’s clinical collaborator.
“This project aims to help clinicians quickly risk stratify patients using real time clinical data, with the goal of widely disseminating this knowledge to help medical practitioners around the world in their approach to treating and monitoring patients suffering from COVID-19.”
Similar studies exist, but only for predictions of general COVID-19 mortality or a patient’s need for ICU care. Furthermore, this approach is significantly more advanced, as it will analyze multiple sources of data and will produce a risk score that is updated as new data is acquired.
This project will shed more light on how COVID-19-related heart injury could result in heart dysfunction and sudden cardiac death, which is critical in the fight against COVID-19. The project will also help clinicians determine which biomarkers are most predictive of adverse clinical outcome.
Once the research team creates and tests their algorithm, they will make it widely available to any interested health care institution to implement.
“By predicting who’s at risk for developing the worst outcomes, health care professionals will be able to undertake the best routes of therapy or primary prevention and save lives,” says Trayanova.
Trayanova, whose work focuses on bringing engineering approaches to the clinical realm, is hopeful that this project will augment the role of engineering in helping patients live longer and lead healthier lives.
With Covaid, neighbors support neighbors during the pandemic
Across the country, a new brand of community movement has often started with an impromptu spreadsheet: neighbors signing up to to deliver groceries, walk dogs, and run various errands to help each other out during the coronavirus pandemic. But when the swell of volunteers rises, the forms can become unnavigable, cluttered with names and information.
A new website, Covaid, aims to provide a simpler platform for these neighbor-to-neighbor aid programs. Two computer science majors and longtime friends, Debanik Purkayastha of Johns Hopkins and Jeffrey Li of Carnegie Mellon, developed the resource in late March to match vulnerable residents with neighbors willing and able to help.
“There are a lot of elderly and immunocompromised people who are afraid to go out, afraid to go to grocery stores or run their daily errands,” says Purkayastha, a Hopkins senior whose second major is biomedical engineering. “We originally built this platform so people can go on the site and reach out for support.”
The idea grew from a spreadsheet making the rounds at Johns Hopkins in the early days of COVID-19 in the U.S., just before campuses closed. Junior Bonnie Jin had created the resource for students to help each other as they moved out—with rides to the airport, for example, or storage space. This soon expanded into a community effort called Baltimore Mutual Aid, reaching to neighborhoods beyond Hopkins campuses and offering a wider range of services.
“A few days before I was packing up and leaving, I saw this spreadsheet going around,” Purkayastha says. “Community members were putting up their contact information and saying, Hey, if you need anything, let me know if I can help. It was very inspiring.”
Once he relocated to his family home outside Philadelphia, Purkayastha got to brainstorming with Li, his friend since middle school. The two were seeing similar mutual aid efforts sprout up in other communities, including Pittsburgh, home to Li’s university.
“The wheels started turning for us to think about, How can we make these things a little better?” Purkayastha says. “I noticed anybody could edit the spreadsheets, there was no automation—there wasn’t really a system. It was a really good idea in concept, but it needed a structure to facilitate things.”
They designed Covaid’s clean blue-and-white interface to present a map of the United States, which zooms in to show volunteers at the neighborhood and even street level. The volunteers—more than 1,675 have registered as of this week—submit a short bio and specify which services they can fulfill, including grocery and medication delivery, pet care, technology on loan, even emotional support. They also indicate times they’re available and whether they have access to a car.
When community members in need of services search the site, the matchmaking occurs through both automation and personal assistance from Covaid’s team—now composed of 20 university students from around the country.
Within the past month, Covaid’s mission has matured to include more formal partnerships with community groups in five cities, with plans for more. In addition to Baltimore Mutual Aid, the team is working with Pittsburgh Mutual Aid, Greater Charlotte Mutual Aid, Delaware Mutual Aid, the CCOM Covaid Task Force in Chicago, and the Indy COVID-19 Neighbor Response Team. The platform allows organizations to transition their existing volunteer resources to a Covaid dashboard, where they can tailor services according to the needs of their community. In some places, for example, the sharpest demand is for monetary donations to buy essentials.
“It’s a really simple platform, which is what’s brilliant about it,” says Seth Bush, a volunteer organizer for Pittsburgh Mutual Aid, which now has more than 60 volunteers signed up for Covaid. “Debanik and Jeff worked with us and listened so closely and so attentively to what we needed. These guys are two amazing human beings.”
Covaid was originally envisioned as a short-term project, Purkayastha muses, back when he believed the pandemic would be over by May. He thought everything would subside before he traveled out to Silicon Valley to begin a summer internship as a software engineer at Facebook—work he’s now planning to perform remotely while continuing to build Covaid’s capacity.
“We’re going to be devoted to this for the foreseeable future,” Purkayastha says.
– Katie Pearce
May 8, 2020
Hopkins BME alum Neil Rens wins prestigious Knight-Hennessy Scholarship
With a lifelong interest in leadership and service, Johns Hopkins alum Neil Rens has worked to make health care more accessible, merging his biomedical engineering background with medicine and health economics to create new models for health care delivery. This fall, he will take this pursuit to the next level as a Knight-Hennessy Scholar at Stanford University.
“The ugly truth is that we already ration health care, we just do it based on a person’s ability to pay,” Rens says. “I prefer a cost-effectiveness approach where we prioritize high-value services and make those affordable for everyone. This approach offers a more equitable and efficient system. On average, outcomes would probably be the same or better than our current system’s, but with less disparity in outcomes between people of different means, health literacies, education levels, [and so on].”
Before graduating from Johns Hopkins in 2016 with a degree in biomedical engineering, Rens created an interactive website to educate the public about the Affordable Care Act and co-founded Aezon, a company that made a handheld device capable of diagnosing 15 different diseases. Rens says he was attracted to the project for its potential to “democratize health,” making care and diagnosis more accessible for those in low-resource areas. He has since ventured into the policy sector, testifying in favor of vaccine-positive legislation in California.
Now, as he completes his third year of medical school at Stanford, Rens will return to his engineering roots to develop new health care delivery models with his Knight-Hennessy Scholarship. The prestigious award, which will fund his pursuit of an MBA, provides up to three years of funding toward a graduate degree at Stanford and is designed to build a community of future global leaders dedicated to finding creative solutions to the world’s greatest challenges. Scholars are selected for their demonstrated academic independence, civic-mindedness, and leadership qualities. The 2020 cohort include 76 scholars.
As a Knight-Hennessy Scholar, Rens will also participate in cohort activities such as an experiential learning tour on civil rights from Selma to Baltimore, which is organized by the JHU-affiliated Thread organization.
“Neil is an outstanding individual whose leadership was amply demonstrated during his time as a student at Hopkins and continues as an active member of our alumni community,” says Ed Schlesinger, dean of JHU’s Whiting School of Engineering. “All of us at the Whiting School are proud of his recognition, and know he will enjoy significant achievement and success in his career.”
While Rens is the first Hopkins affiliate to be named a Knight-Hennessy Scholar, this is not his first time winning a prestigious award. His company Aezon was one of seven finalists for the $10 million Qualcomm Tricorder XPRIZE; at the time, Aezon was a humble team of Hopkins students running against 300 entrants consisting mostly of startups. In 2016, he was named a finalist for the prestigious Rhodes Scholarship, and later that academic year he was awarded a Fulbright grant to pursue an MSc in health economics, policy, and law in the Netherlands, both of which he applied for through JHU’s National Fellowships Program.
“I think one of the things that makes Neil stand out is not only his desire to take advantage of every opportunity, but also his ability to manage his time,” says Eileen Haase, program chair of Applied Biomedical Engineering at JHU and mentor to Rens. “Neil is also resilient. He has been awarded many honors—but he has also faced rejection. Whenever he misses out on an opportunity, he moves right along and looks for the next one.”
In addition to his enterprising spirit, those who know Rens admire him for his heart for service. He has leveraged his opportunities to help those who experience systemic disadvantage; his service work includes spending a summer in Rwanda fixing medical equipment and time spent working as a delegate and vice chair for the American Medical Association and California Medical Association. This spirit for service is reflected in the work Rens looks toward now as a Knight-Hennessy Scholar as he strives to improve the cost-effectiveness and consequent accessibility of health care.
“Visiting other countries and studying their approaches to health care has been enriching and humbling,” Rens says. “Each community has its own priorities, and even when there are common goals across countries, their unique cultural contexts necessitate tailored approaches. … Despite the varied priorities and circumstances, we can gain valuable insights from around the world. I am excited to synthesize these ideas and work with local stakeholders to implement culturally sensitive improvements to health care systems in the U.S. and abroad.”
– Jacob Budenz
May 6, 2020
Two from Hopkins BME recognized at Young Investigators’ Day
Young Investigators’ Day at Johns Hopkins University was established in 1978 to recognize the outstanding research contributions made by our trainees: medical and graduate students, postdoctoral and clinical fellows and residents. The annual celebration includes brief presentations by the awardees, a poster presentation and reception. Awardees each receive a cash prize as well as recognition during convocation ceremonies. Many Young Investigators’ Day winners have gone on to very successful careers in biomedical research.
Each award carries a distinct honor and specific history to the legacy of biomedical research here at Johns Hopkins, and a number of named awards were established and are generously supported by friends and family in memory of past students or faculty members.
Award winners affiliated with Hopkins BME include:
Chen Zhao – The Bao Gyo Jung Research Award (2008)
Macrophages are a class of innate immune cells that play essential roles in the progression of a variety of major human diseases. My research project is to build multiscale computational models to mechanistically simulate and investigate the role of macrophages, especially their phenotypic polarization, in the regulation of blood vessel formation, inflammation and immune response in disease settings such as cancer and peripheral arterial disease. These data-driven computational platforms that I built were used to identify and evaluate novel therapeutic strategies, with the potential to improve disease outcomes in patients. My research adviser is Aleksander S. Popel, Ph.D., in the Department of Biomedical Engineering.
Every movement begins and ends in a period of stillness. In the Laboratory for Computational Motor Control (the Shadmehr Lab), we study how the brain controls these different periods of motor activity. While decades of research have demonstrated that one area of the brain, the primary motor cortex, is critical for the execution of a movement, we know comparatively little about how the brain holds the arm still in a desired posture. In our recent work, we wondered if the brain holds the arm still using a strategy similar to that of the eye. For the eye, there are some neurons that produce a “moving” signal that corresponds to the velocity of the eye. However, there is a separate set of neurons that produce a “holding” signal that corresponds to the position of the eye. Much like the formula “distance equals rate multiplied by time,” the holding neurons calculate the “holding” signal by mathematically integrating the “moving” signal over time. Through a sequence of experiments involving over 200 healthy humans, 14 stroke patients, and four non-human primates, we discovered that a very similar integration process is used to hold the arm still. Critically, because reach integration was unimpaired in patients who suffered from cortical strokes, our work suggests that there are separate areas of the brain that move the arm and hold the arm still, as for the eye. These findings may help us understand why some neurological conditions can lead to impairment in movements and abnormal postures.
Gene variant in noncoding DNA linked to heart failure
When scientists scour the genome for disease-causing culprits, they wouldn’t ordinarily look in so-called noncoding regions, areas of repetitive DNA that do not code for proteins. Yet, that’s exactly where Johns Hopkins scientists found genomic variations in a new study of people with heart failure.
Marios Arvanitis, M.D., a postdoctoral cardiology fellow at the Johns Hopkins University School of Medicine, and the study’s first author, completed a meta-analysis of data from more than 400,000 people and discovered variations in a noncoding region of chromosome 1 that were associated with the development of clinical heart failure. He confirmed the finding in another group of more than 1 million study participants.
The scientists’ next challenge was to uncover the function of the DNA in the noncoding region where the variations were found. “This area of the genome is probably involved in regulating how genes are turned on and off, but we wanted to know which gene the code controlled,” says Alexis Battle, Ph.D., associate professor of biomedical engineering and computer science at The Johns Hopkins University and senior author of the study.
To determine the noncoding region’s function, the scientists made a 3D model of developing human cardiac cells and used computer algorithms to determine the DNA’s structure within the cells. They found that the noncoding region folds up and ‘touches’ a nearby gene called ACTN2, which makes a protein important for the structure of cardiac cells.
Then, the investigators used the CRISPR gene-cutting tool to remove the noncoding region on chromosome 1 in lab grown cardiac cells and found that gene expression of ACTN2 drops by 47% and no other genes in that region were disrupted.
“This is a strong example of a connection between noncoding and coding regions of the genome,” says Battle. “While the variations occur in a relatively small percentage of people with heart failure, our findings may point to a genetic pathway for which a treatment can be developed — not only for people with the gene variant, but perhaps others with heart failure.”
Researchers create nanoparticle with ‘look and feel’ of red blood cells to soak up toxins
Red blood cells not only carry oxygen from one part of the body to another, they also act as sponges in the circulatory system, soaking up toxins such as poisons shed from infections. The more red blood cells available in the blood system, the faster the recovery from toxin-related threats to the body.
Johns Hopkins biomedical engineer Jordan Green, Ph.D., and his colleagues have developed a nanoparticle that has the shape and “skin” of red blood cells. The red blood cell mimics can be injected into the bloodstream and circulate within vessels for long periods to absorb toxic substances.
Green says that other research groups have developed sphere-shaped nanoparticles as toxic sponges, but his team found that more closely matching the shape of the oxygen-carrying cells is a critical step forward.
“Most nanoparticles are spheres, but we hypothesized that mimicking the elongated shape of red blood cells may work better — in part because it has more surface area — to absorb toxins,” says Green, professor of biomedical engineering, ophthalmology, oncology, neurosurgery, materials science and engineering, and chemical and biomolecular engineering at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center.
First author Elana Ben-Akiva, Green and the Johns Hopkins team used biodegradable plastic-coated nanoparticles and stretched them to create elongated shapes. Then, they wrapped the lengthened nanoparticles in the membranes, or outer coating, of mouse red blood cells.
Next, the team injected the newly created nanoparticles into mice that had a lethal dose of alpha-toxin from the Staphylococcus aureus bacteria to evaluate the ability of the nanoparticles to serve as a sepsis detoxification therapy. Sepsis is a fatal condition caused by the release of toxins from bacteria into the bloodstream.
Compared with uncoated, spherical nanoparticles, Green and his team found that their red blood cell-mimicking nanoparticles stayed approximately 600% longer in the bloodstream of mice before being engulfed by immune system cells. Half of the toxin-laden mice survived long term — meaning more than one week after being treated — with the newly created nanoparticles, compared with a survival time of only several hours for mice in the control group.
“The more we learn about biology, the more we can engineer treatments to match it, and the better our treatments work,” says Green.