Research News Tip Sheet: Story Ideas From Johns Hopkins


During the COVID-19 pandemic, Johns Hopkins Medicine Media Relations is focused on disseminating current, accurate and useful information to the public via the media. As part of that effort, we are distributing our “COVID-19 Tip Sheet: Story Ideas from Johns Hopkins” every Tuesday throughout the duration of the outbreak.

We also want you to continue having access to the latest Johns Hopkins Medicine research achievements and clinical advances, so we are issuing a second tip sheet every Thursday, covering topics not related to COVID-19 or the SARS-CoV-2 virus.

Stories associated with journal publications provide a link to the paper. Interviews with the researchers featured may be arranged by contacting the media representatives listed.


Media Contact: Vanessa Wasta, M.B.A.

An electron microscopic image of a red blood cell-coated nanoparticle.

Credit: Elana Ben-Akiva, Johns Hopkins Medicine

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.

A report on the work appears in the April 15, 2020, issue of the journal Science Advances.

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.


Media Contact: Brian Waters

Smoking a cigarette can have long-term damaging effects on not only the smoker’s lungs, but the lungs of people surrounding the smoker as well. Although there are many reported instances of vaping-induced lung injuries from electronic cigarettes, secondhand vaping smoke injuries have yet to be documented. That is, until now. In the Feb. 19, 2020, issue of the journal BMJ Case Reports, Johns Hopkins Medicine researchers report identifying a patient they believe developed an inflammatory lung condition from secondhand e-cigarette smoke.

The researchers diagnosed a 37-year-old woman with hypersensitivity pneumonitis, a rare immune system disorder that can be caused by exposure to allergens in the environment such as animal dander, household mold or chemicals. The condition causes inflammation in the tissues surrounding the air sacs of the lungs, leading to scarring and possible permanent damage. In this specific case, the researchers noted that the woman’s lungs are somewhat weak as she was born prematurely and that her husband is a frequent e-cigarette user.

In 2016, the patient was diagnosed with asthma but continued to wheeze after treatment. A bronchoscopy failed to determine an underlying cause for her respiratory problem.

Johns Hopkins physicians, including Panagis Galiatsatos, M.D., M.H.S., first saw the woman two years later. Galiatsatos, assistant professor of pulmonary and critical care medicine at the Johns Hopkins University School of Medicine, and his colleagues reviewed the patient’s medical history, conducted tests and concluded that she had hypersensitivity pneumonitis. They could only point to one possible source for the responsible irritant: the smoke from her husband’s e-cigarettes.

“This is the first case that we are aware of that reports a dire health consequence of secondhand smoke from vaping,” Galiatsatos says. “Now that we know people with more sensitive lungs may be more at risk for complications due to someone else’s vaping, we will likely document more of these cases in the future.”

Galiatsatos has recommended that the woman avoid any firsthand or secondhand exposure to traditional or e-cigarettes. The researchers say that future studies should focus on whether or not secondhand smoke from e-cigarettes can lead to lung damage in healthy people, even if they do not show outward symptoms.


Media Contact: Michael E. Newman

Like a parent of teenagers at a party, Mother Nature depends on chaperones to keep one of her charges, the immune system, in line so that it doesn’t mistakenly attack normal cells, tissues and organs in our bodies. A recent study by Johns Hopkins Medicine researchers has demonstrated that in mice — and probably humans as well — one biological chaperone may play a key role in protection against such attacks, known as autoimmune responses, which are a hallmark of diseases such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes.

The researchers detailed their study in the Feb. 18, 2020, issue of the journal PLOS Biology (see news release for more details).

“Short protein fragments that come from bacteria, viruses and other pathogens act as antigens to trigger our immune system to remove the invaders, a process that depends on other proteins acting and interacting in a specific sequence of events,” says Scheherazade Sadegh-Nasseri, Ph.D., professor of pathology at the Johns Hopkins University School of Medicine. “In our mouse study, we have shown that a specific disruption in this regimen can redirect the immune system to turn against a healthy body — something that we believe also is likely occurring in humans.”

In their effort to identify this “chaperone disruption,” the researchers relied on the fact that for a mammal’s immune system to trigger a response, antigenic proteins must be exposed, or “presented,” to immune cells known as T lymphocytes, or T cells.

Two chaperone proteins in humans, DO and DM, work together to assist this presentation so that the immune system correctly determines that the protein fragments are foreign and not from normal, healthy components of the body. While previous research has provided a good understanding of DM’s role in this process, the function of DO has remained unclear until now.

To better define DO’s involvement in immunity and autoimmunity, Sadegh-Nasseri and her colleagues focused on H2-O, the chaperone protein in mice that is comparable to DO in humans.

The researchers found that H2-O in mice, and likely DO in humans, may be helping select the stronger binding protein fragments — the ones targeted as being from antigens — for presentation, ensuring that the immune response is highly specific. Using two different laboratory-induced autoimmune responses in mice, they also discovered that the absence of H2-O disrupts normal helper T cell function and allows full-blown autoimmune disorders — similar to rheumatoid arthritis and multiple sclerosis in humans — to occur.

By linking the absence of a key chaperone protein, H2-O, with two experimental autoimmune disorders in mice, the researchers say this points to a similar impact in humans if DO is not present to keep the immune system focused on true invaders.

“We know that DO evolved later than DM in warm-blooded mammals, so perhaps DO’s chaperoning role was nature’s solution for preventing autoimmune disorders,” Sadegh-Nasseri says. “Better understanding of this role could lead to improved diagnostic techniques and therapies for such diseases.”


Media Contact: Vanessa McMains, Ph.D.

The genetic condition arrhythmogenic right ventricular cardiomyopathy (ARVC) causes fat to build up in heart tissue, which can lead to irregular heartbeats and sudden cardiac death. By following the structural changes in the hearts in people with the disorder over time, Johns Hopkins Medicine researchers believe they may have found a biomarker that could predict the progression of the disease and predict who would need aggressive treatment sooner to prevent death. In their new study, published in the Journal of the American Heart Association on April 9, 2020, the researchers reported that monitoring the increasing stiffness of the right ventricular chamber of the heart was linked to structural changes indicating worsening of disease.

“If we can confirm these structural changes are linked with actual cardiovascular events, such as irregular heartbeat, heart failure or sudden death, then we can see if using this measurement can predict who would most benefit from earlier intervention,” says Allison Hays, M.D., associate professor of medicine at the Johns Hopkins University School of Medicine. “The ultimate goal would be to save more lives.”

Their study used images from echocardiograms repeated on average of 3.5 years apart in 40 patients with ARVC. In the study, the researchers found that those patients with abnormal function in the right ventricle (measured using a technique called strain imaging) were 18 times more likely to have worsening of their heart disease over time, defined by a progressive increase in size of the right ventricle and reduced ability to pump blood out of the heart.


Media Contact: Valerie Mehl

A low-dose, two-drug epigenetic (the addition of chemical compounds to genes to regulate their activity) therapy used for more than a decade to attack tumor cells also appears to target certain tumor-promoting immune system cells, limits the suppression of other cancer-fighting cells, and reduces the spread and recurrence of three human cancer types. That’s according to new research in mice from the Johns Hopkins Kimmel Cancer Center and Peking University Cancer Hospital and Institute in China.

If confirmed in further studies, the findings, described in the Feb. 26, 2020, online issue of Nature, could advance efforts to stem postoperative and other metastases — the migration of cancer cells to sites beyond a tumor’s original location and the process responsible for the vast majority of cancer deaths.

The drugs studied, 5-azacitidine and entinostat, target epigenetic factors, chemical changes to DNA and the packaging of DNA in the nucleus of cells that, in the case of cancers, shut down tumor suppressor genes. In the new study, the drugs also blocked the activity of cells in the immune system called myeloid-derived suppressor cells (MDSCs), which are known to suppress another immune system component, cancer-killing T cells.

A team led by Malcolm Brock, M.D., director of the Kimmel Cancer Center’s clinical and translational research in thoracic surgery, found that in mice, the treatment — especially when given after surgery to remove a tumor — significantly decreased the migration of MDSCs to the lung. It also significantly limited the growth and formation of metastatic tumors in the animals’ lungs as compared with untreated mice.

The medications stopped cells from setting up a cancer-welcoming environment, called a premetastatic niche, which sometimes occurs after surgical removal of a cancerous tumor. Chemically reprogrammed by the drugs, MDSCs were less successful at accumulating in distant organs and at paving the way for the spread of lung, esophageal and breast cancer tissue implanted in the mice.

Mice implanted with non-small cell lung cancer, esophageal squamous cell carcinoma or breast cancer tumors had significantly longer periods of disease remission and overall survival when they received the drugs after their implanted tumors were removed. Low-dose therapy with the two drugs has been demonstrated in other cancer types to be well-tolerated in humans.