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The U.S. Food and Drug Administration has approved a novel therapy for patients with metastatic or inoperable melanoma, an aggressive type of skin cancer. The treatment, developed based on original research conducted at the Johns Hopkins Kimmel Cancer Center, is comprised of two immunotherapy agents, relatlimab (anti-LAG-3) and nivolumab (anti-PD-1), which delayed time to cancer progression significantly more than nivolumab alone in a global, multi-center clinical trial. Results from the study, called RELATIVITY-047, were published in The New England Journal of Medicine on Jan. 6, 2022. Evan J. Lipson, M.D., an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center and Bloomberg~Kimmel Institute for Cancer Immunotherapy, is a co-author of the study and presented initial findings at the 2021 American Society of Clinical Oncology (ASCO) annual meeting.
“The FDA’s approval of this novel combination therapy is an exciting development for all of us in the melanoma community,” says Dr. Lipson. “Our collaborative research with scientists and physicians worldwide has demonstrated that targeting LAG-3 effectively activates the immune system against cancer and has established the LAG-3 pathway as the third immune checkpoint pathway in history, after CTLA-4 and PD-1, for which blockade has a clinical benefit.”
Checkpoint inhibitor immunotherapy works by blocking specific proteins on the surfaces of cells that help cancer evade the body’s immune system. Blocking these checkpoints helps the immune system fight and eliminate cancer.
In the RELATIVITY-047 trial, 714 patients with advanced, previously untreated melanoma were randomized to receive either relatlimab plus nivolumab, or nivolumab alone. Median progression-free survival — the length of time that cancer does not worsen — was 10.2 months among patients who received the combination treatment, significantly longer than the 4.6 months seen among those who received nivolumab alone. At one year, progression-free survival was 48% for patients receiving combination therapy and 37% for those receiving nivolumab alone.
Nivolumab acts on a protein called PD-1 and is FDA-approved for treating melanoma and several other cancer types. Relatlimab blocks signaling of an inhibitory protein called LAG-3 displayed on immune system T cells, reinvigorating their anti-tumor activity.
The anti-tumor effects of LAG-3 blockade were originally co-discovered by scientists at the Bloomberg~Kimmel Institute. Preclinical studies of the combination therapy in mice started at Johns Hopkins in 2010, with a grant from the Melanoma Research Alliance to Johns Hopkins investigators Suzanne L. Topalian, M.D., professor of surgery and oncology at Johns Hopkins, and Drew M. Pardoll, M.D., Ph.D., director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy and co-director of the Cancer Immunology Program at the Johns Hopkins Kimmel Cancer Center.
The RELATIVITY-047 trial was sponsored by Bristol-Myers Squibb Co. Dr. Lipson is a paid consultant and advisory board member. Dr. Pardoll receives research grant support. Dr. Topalian is a paid consultant and receives research grant support. Dr. Pardoll is an inventor on a patent on the blockade of LAG-3 for the treatment of cancer. Under a license agreement between BMS and the Johns Hopkins University, Dr. Pardoll, and the University are entitled to royalty distributions related to the technology cited in the study and discussed in this publication. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies.
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Materials provided by Johns Hopkins Medicine. Note: Content may be edited for style and length.

Over the past four decades, global cases of Type 2 diabetes mellitus have skyrocketed. According to the World Health Organization, the number of people estimated to have the disease jumped from 108 million in 1980 to 422 million in 2014, with the fastest growth observed in low- and middle-income countries.
Although the disease is common, there is still much research left to be done to fully understand it. For instance, while diabetes is linked to obesity, researchers still do not know the exact reasons why obesity causes diabetes.
In a new paper published in the journal Obesity Reviews, Concordia researchers Kerri Delaney and Sylvia Santosa look at how fat tissue from different parts of the body may lead to diabetes onset in men and women. They reviewed almost 200 hundred scientific papers looking for a deeper understanding of how fat operates at the surface and tissue level, and the mechanisms by which that tissue contributes to diabetes onset.
“There are many different theories about how diabetes develops, and the one that we explore posits that different regions of fat tissue contributes to disease risk differently,” says Kerri Delaney, a PhD candidate at Concordia’s PERFORM Centre and the paper’s lead author. “So the big question is, how do the different depots uniquely contribute to its development, and is this contribution different in men and women?”
From surface to cell level
Men and women store fat in different places. Diabetes, like many other diseases, is closely associated with abdominal fat. Women tend to store that fat just under the skin. This is known as subcutaneous fat. In men, abdominal fat is stored around the organs. This is visceral fat.
Fat appears to exhibit different features in men and women. They grow differently, are dispersed differently and interact with the inflammatory and immune system differently. For example, in men fat tissue expands because the fat cells grow in size; in women, fat cells multiply and increase in number. This changes with the loss of the protective hormone estrogen that disappears with menopause and may explain why men are more susceptible to diabetes earlier in life than women.
Working from the hypothesis that diabetes risk is driven by expansions of visceral fat in men and of subcutaneous fat in women, the researchers then looked through the papers to see what was happening in the cell-level microenvironments.
Though more research is needed, there were overall differences observed in the immune cell, hormone, and cell signalling level in men and women that seem to support different origins in diabetes between the sexes.
Delaney and Santosa hope that by identifying how diabetes risks are different in men and women, clinical approaches to treatment of the disease can be better defined between the sexes.
“Currently, the treatment of diabetes is similar for men and women,” says Santosa, an associate professor in the department of Health, Kinesiology and Applied Physiology. “If we understood the differences between them better, we could consider these mechanisms in recommending treatments to men and women based on how diabetes medications work.”
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Materials provided by Concordia University. Original written by Patrick Lejtenyi. Note: Content may be edited for style and length.

The lower airways of patients with cystic fibrosis (CF) have unique biochemical features that correlate with the complex communities of lung bacteria typical of this disease, according to a multicenter study led by researchers from Ann & Robert H. Lurie Children’s Hospital of Chicago. These findings offer insights into the underlying biological mechanisms driving infection and inflammation in the CF lungs, and may help develop novel targeted therapies and more precise diagnostics to improve the care of children with CF. Results were published in the journal Frontiers of Cellular and Infection Microbiology.
Chronic airway infection and inflammation resulting in progressive, obstructive lung disease is the leading cause of illness and death in people with CF. To better understand the biological mechanisms of infection and inflammation, in a study conducted Lurie Children’s in collaboration with researchers at Children’s Hospital Colorado and the University of Minnesota, several metabolites were measured in 90 bronchoalveolar lavage fluid (BALF) samples acquired from bronchoscopy. These lower airway samples were collected from children with and without CF. Researchers also used genetic sequencing to characterize the bacterial communities present in these samples, which were then correlated to the metabolites in the lungs.
“Our study was the first to both examine these metabolites in lower airway samples and identify networks of relationships between metabolites and lower airway bacterial communities,” said lead author Jack O’Connor from Lurie Children’s. “We discovered metabolite biomarkers that could be related to biochemical processes associated with increased inflammation and bacterial burden in the CF lung. These features that are unique to CF lung biology could eventually aid the development of new treatments and diagnostics.”
Two metabolomic characteristics — increased amino acids and decreased acylcarnitines — were found to be unique to CF and potentially could serve as biomarkers of the inflammation and infection. Additionally, a metabolite of interest, L-methionine-S-oxide, was positively corrected with the abundance of Staphylococcus, a traditional CF pathogen, and negatively correlated with the abundance of anaerobic bacteria of interest in the development of chronic CF lung disease. The study provides some interesting clues about what may be happening biologically in the CF airway.
“Our findings are in the very early stages of research and are not yet ready for clinical applications,” said senior author Theresa Laguna, MD, MSCS, Division Head of Pulmonary and Sleep Medicine at Lurie Children’s and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “Our results lay important groundwork for future studies that ultimately will advance clinical care for children with CF.”
Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through the Stanley Manne Children’s Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine.
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Materials provided by Ann & Robert H. Lurie Children’s Hospital of Chicago. Note: Content may be edited for style and length.

A multicenter research team co-led by The University of Texas MD Anderson Cancer Center developed the first drug to treat the uncontrolled secretion of mucins in the airways, which causes potentially life-threatening symptoms in millions of Americans with asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), as well as lung disease resulting from cancer and cancer treatment. The study was published today in Nature.
“Mucus is a significant problem in pulmonary medicine, because in people with these common lung diseases, thick mucus can block the airways and cause symptoms ranging from a mild cough to very serious decreases in lung function,” said Burton Dickey, M.D., professor of Pulmonary Medicine and co-corresponding author of the study. “Most drugs for these conditions work to reduce inflammation or expand the airways to help people breathe better, but mucus is the most serious issue. Our research has created the first drug that would stop the secretion of mucins in its tracks.”
Muco-obstructive lung diseases affect hundreds of millions of people worldwide. In the U.S., about 25 million people have asthma, 16 million adults have been diagnosed with COPD and CF is the most common life-threatening, genetic disease. Many cancer patients end up with lung disease because their cancer treatments or the cancer itself leaves them immunocompromised.
Normally, mucins are gradually released into the airways, where they absorb water and form a thin layer of protective mucus that traps pathogens and is easily cleared by cilia. In muco-obstructive lung diseases, high volumes of mucins are suddenly released and, unable to absorb enough water, result in a thick mucus that can plug airways and impair lung function.
Dickey’s lab began studying mucin secretion two decades ago and previously identified the key genes and proteins involved, showing how synaptotagmin and a SNARE complex, similar to that found in neurons, contribute to the key process of Ca2+-triggered membrane fusion.
“We built up a picture of what the secretory machinery looked like and we knew all of the major players,” Dickey said. “Once we had an idea of how all the pieces worked together, we determined synaptotagmin-2 (Syt2) was the best protein to target to block mucin secretion because it only becomes activated with a high level of stimulation. Therefore, blocking the activity of Syt2 should prevent sudden massive mucin release without impairing slow, steady baseline mucin secretion that is required for airway health.”
In this study, a collaborative effort between MD Anderson, Stanford Medicine and Ulm University, the researchers verified Syt2 as a viable therapeutic target protein in several types of preclinical models. Philip Jones, Ph.D., vice president of Therapeutics Discovery and head of the Institute for Applied Cancer Science, designed a hydrocarbon-stapled peptide, SP9, to block Syt2, based on structures developed by the Stanford collaborators, including senior co-corresponding author Axel Brunger, Ph.D., professor of Molecular and Cellular Physiology.
Stapled peptides are a recent therapeutic development involving modified amino acids that form hydrocarbon crossbridges to hold their structure rigid so they can bind to a protein target and show enhanced stability. Stapled peptides have been used to treat other diseases, including cancer, but SP9 would represent the first stapled peptide to be used as an inhaled therapeutic.
In a reconstituted system model in Brunger’s Stanford laboratory, Ying Lai, Ph.D., used SP9 to successfully disrupt Ca2+-triggered membrane fusion. The Ulm laboratory of Manfred Frick, Ph.D., used SP9 conjugated to a cell penetrating peptide in cultured epithelial cells to inhibit rapid mucin secretion. The Dickey laboratory then used an aerosolized version in a mouse model to confirm the drug reduced mucin secretion and airway blockage by mucus. Importantly, SP9 did not affect the slow-release pathway for normal mucin secretion.
“An inhaled drug like this could help someone during an acute attack of airway disease by stopping the rapid secretion of mucin and, by extension, avoiding production of thick mucus. You can’t move air through an airway that’s plugged,” Dickey said. “In asthma, COPD and CF, it’s been shown that persistent plugs drive the most serious disease. Now we have a drug that could be very important if it’s shown to work in clinical trials.”
The stapled peptide SP9 will be further refined before moving to human studies, as is typical for therapeutics at this stage of development, and may enter clinical trials in a couple of years.
Dickey and co-authors are inventors on a patent application related to SP9. The study was supported by the National Institutes of Health (R01 HL129795, R21 AI137319) and the Cystic Fibrosis Foundation. 

For life to survive, it needs to respond to challenges, particularly by adapting the activity of its immune system. As we have seen with Covid, outside infectious agents are constantly trying to gain a foothold within the body. But how can immune cells move into new tissues to find and destroy such infections? By investigating this crucial process, Professor Daria Siekhaus and Dr. Shamsi Emtenani from her group at ISTA ended up answering an even bigger question: What governs the energy needed for cell invasion?
They discovered a two-fold program that boosts energy production inside immune cells, thereby supplying the power needed for their invasion into tissues. This novel pathway is governed by a previously unstudied protein which they named Atossa after a Persian queen. While the experiments were done in the fruit fly, the researchers’ results show that similar proteins in mammals exhibit the same function. “There is a plethora of potential for how this work can lead to new perspectives of human physiology, because boosting energy production is essential in so many cells throughout the human body,” says lead author Emtenani. Their collaborative work with the University of Albany, University of Toronto, the CeMM Research Center and the Vienna BioCenter is now published in the journal of the European Molecular Biology Organization (EMBO).
Atossa, ruling to boost energy
For cells, pushing surroundings out of the way and moving into tissues is energetically costly. The immune system ramps up energy by using mitochondria, the cell’s internal powerhouse. Mitochondria turn various constituents like sugar into ATP, the cellular currency of energy. The researchers have now found that one protein, Atossa, orchestrates a cascade that regulates and improves the capacity of mitochondria to produce energy.
“Atossa acts as both an accelerator pedal and a gear shift,” explains Siekhaus. “First, the protein activates two metabolic enzymes that help send more fuel into the mitochondrial factory, and second, it shifts the mitochondria into a higher gear.” This gear shift is caused by Atossa’s increasing the levels of the protein Porthos, an RNA helicase named after one of the three musketeers known for their faithfulness in serving their queen. Then, Porthos aids the assembly of the machinery that enables protein production through translation, including many that raise mitochondrial activity and thus energy production.
Pioneering fly work relevant for human health
By live imaging of fruit fly embryos, the researchers were able to detect a clear reduction in cell migration in the absence of Atossa. Also, Atossa’s function is only needed in pioneer cells. Much like an expedition through a thicket, the first cells do the hard work of clearing a path with the machete and thus need more energy. With the support of collaborator Dr. Thomas Köcher from the Vienna BioCenter, the ISTA scientists compared the energy levels with and without the Atossa gene and confirmed that Atossa indeed enhances them.

Researchers at Johns Hopkins Children’s Center report evidence from lab experiments that a chemical derived from a compound found abundantly in broccoli and other cruciferous plants may offer a potentially new and potent weapon against the viruses that cause COVID-19 and the common cold. COVID-19 has already killed more than 6 million people worldwide, and studies have shown that common colds cost an estimated economic loss of $25 billion in the U.S. alone each year.
In a study described March 18 in the Nature journal Communications Biology, the scientists showed that sulforaphane, a plant-derived chemical, known as a phytochemical, already found to have anti-cancer effects, can inhibit the replication of SARS-CoV-2, the coronavirus that causes COVID-19, and another human coronavirus in cells and mice.
While the results are promising, the researchers caution the public against rushing to buy sulforaphane supplements available online and in stores, noting that studies of sulforaphane in humans are necessary before the chemical is proven effective, and emphasizing the lack of regulation covering such supplements.
Sulforaphane’s natural precursor is particularly abundant in broccoli, cabbage, kale and Brussels sprouts. First identified as a “chemopreventive” compound by a team of Johns Hopkins scientists decades ago, natural sulforaphane is derived from common food sources, such as broccoli seeds, sprouts and mature plants, as well as infusions of sprouts or seeds for drinking. Previous studies, including those at Johns Hopkins Medicine, have shown sulforaphane to have cancer and infection-prevention properties by way of interfering with certain cellular processes.
“When the COVID-19 pandemic started, our multidisciplinary research teams switched our investigations of other viruses and bacteria to focus on a potential treatment for what was then a challenging new virus for us,” says Children’s Center microbiologist Lori Jones-Brando, Ph.D., an assistant professor of pediatrics at the Johns Hopkins University School of Medicine and the senior author of the paper. “I was screening multiple compounds for anti-coronavirus activity and decided to try sulforaphane since it has shown modest activity against other microbial agents that we study.” The researchers used purified, synthetic sulforaphane purchased from commercial chemical suppliers in their experiments.
In one experiment, the research team first exposed cells to sulforaphane for one to two hours before infecting the cells with SARS-CoV-2 and the common cold coronavirus, HCoV-OC43. They found that low micromolar (µM) concentrations of sulforaphane (2.4-31 µM) reduced the replication by 50% of six strains of SARS-CoV-2, including the delta and omicron variants, as well as that of the HCoV-OC43 coronavirus. The investigators also observed similar results with cells that had been previously infected with the viruses, in which the protective effects of sulforaphane were seen even with an already established virus infection.

Engineering and medical researchers at the University of Minnesota Twin Cities and Mayo Clinic have developed a new process for successfully storing specialized pancreatic islet cells at very low temperatures and rewarming them, enabling the potential for on-demand islet transplantation. The breakthrough discovery in cryopreservation is a major step forward in a cure for diabetes.
According to the Centers for Disease Control and Prevention, diabetes is the seventh leading cause of death in the United States, accounting for nearly 90,000 deaths each year. While diabetes management has improved greatly over the 100 years since the discovery of insulin, even the most modern methods remain a treatment for the condition rather than a cure.
Pancreatic islet cell transplantation — a process where doctors take groups of cells from a healthy pancreas and transfer them to a recipient, which then begin to make and release insulin on their own — is one method being explored to cure diabetes. One of the main limitations of this approach is that transplants from a single donor are often insufficient to achieve insulin independence in the recipient. Frequently, two, three, or more donor islet infusions are required, which adds risks associated with repeated surgical interventions and multiple rounds of strong immunosuppression induction.
One strategy for overcoming the donor supply problem is to pool islets from multiple donors, achieving high islet dosage with a single infusion. This process is limited by the inability to safely store islets for long periods of time. Previous research has shown storage to be limited to 48 to 72 hours before transplantation.
In new research published in Nature Medicine, University of Minnesota researchers have developed a new method of islet cryopreservation that solves the storage problem by enabling quality-controlled, long-term preservation of the islet cells that can be pooled and used for transplant.
The study was led by John Bischof, PhD, a mechanical engineering Distinguished McKnight University Professor and director of the University’s Institute for Engineering in Medicine, and Erik Finger, MD, PhD, associate professor of surgery in the University of Minnesota Medical School, M Health Fairview. Both Bischof and Finger are a part of the National Science Foundation Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio) and co-direct the Center for Organ Preservation at the University of Minnesota.

Being conceived via assisted reproductive technology (ART), such as IVF, may provide some advantages in quality of life in adulthood, according to the results of a new study.
The results of the study, published in Human Fertility, offer reassuring news for people who have been conceived with ART — and those who need to use the technology to conceive.
“Our findings suggest that being ART-conceived can provide some advantages on quality of life in adulthood, independent of other psychosocial factors,” said lead author Karin Hammarberg of Monash University, Melbourne, Australia. “Together with previous evidence that adults conceived by ART have similar physical health to those who were naturally conceived, this is reassuring for people who were conceived with ART — and those who need ART to conceive.”
In the more than four decades since the first birth following in vitro fertilisation (IVF) in 1978, more than 8 million children have been born as a result of ART. In that time, many studies have evaluated the physical health, development and psychosocial well-being of ART-conceived children compared with those naturally conceived (NC). But currently, there is less known about the health and quality of life of adults who were conceived by ART.
This study involved 193 young adults who were conceived through ART and 86 through NC in the state of Victoria, Australia. These participants completed questionnaires, which included a standardised quality of life measure (World Health Organisation Quality of Life — Brief Assessment (WHOQoL-BREF)), when aged 18-28 years (T1) and again when aged 22-35 years (T2). The WHOQoL-BREF assesses four domains of quality of life: 1) physical 2) psychosocial 3) social relationships and 4) environment.
The researchers looked at the associations between factors present at T1 (mode of conception, the mother’s age when the participant was born, sexual orientation, family financial situation in secondary school, perceptions of own weight, number of close friends, frequency of vigorous exercise and quality of relationships with parents) and the scores on the four domains of WHOQoL-BREF at T2.
After making statistical adjustments to account for other psychosocial factors present in young adulthood, the results showed that being ART-conceived was strongly linked with higher scores (better quality of life) on both the social relationships and environment WHOQoL-BREF domains at T2. In addition, having less psychological distress, a more positive relationship with parents, a better financial situation, and perceptions of being about the right weight at T1 were associated with higher scores on one or more WHOQoL-BREF domains at T2.
“Children conceived via ART are nowadays a substantial part of the population — and it’s important to continue to evaluate the long-term effects of ART on their physical health and well-being as they progress through adolescence into adulthood,” said Hammarberg. “When accounting for other factors present in young adulthood, being ART-conceived appears to confer some advantages in quality of life. Perhaps unsurprisingly, we also found that, independently of how the person was conceived, having a better relationship with parents, less psychological distress, and a better family financial situation in young adulthood contributed to a better adult quality of life.”
This is the first study to explore the contributions of being conceived with ART and psychosocial factors present in young adulthood to the quality of life of adults. While the findings are reassuring, they should be be interpreted with caution because many of those who took part in the first study did not take part in the follow-up study.
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Materials provided by Taylor & Francis Group. Note: Content may be edited for style and length.

An international research team led by scientists at Georgetown University has found that humans might give viruses back to animals more often than previously understood.
In a study published March 22 in Ecology Letters, the authors describe nearly one hundred different cases where diseases have undergone “spillback” from humans back into wild animals, much like how SARS-CoV-2 has been able to spread in mink farms, zoo lions and tigers, and wild white-tailed deer.
“There has understandably been an enormous amount of interest in human-to-wild animal pathogen transmission in light of the pandemic,” says Gregory Albery, Ph.D., a postdoctoral fellow in the Department of Biology at Georgetown University and the study’s senior author. “To help guide conversations and policy surrounding spillback of our pathogens in the future, we went digging through the literature to see how the process has manifested in the past.”
In their new study, Albery and colleagues found that almost half of the incidents identified occurred in captive settings like zoos, where veterinarians keep a close eye on animals’ health and are more likely to notice when a virus makes the jump. Additionally, more than half of cases they found were human-to-primate transmission, an unsurprising result both because pathogens find it easier to jump between closely-related hosts, and because wild populations of endangered great apes are so carefully monitored.
“This supports the idea that we’re more likely to detect pathogens in the places we spend a lot of time and effort looking, with a disproportionate number of studies focusing on charismatic animals at zoos or in close proximity to humans” says Anna Fagre, DVM, Ph.D., MPH, a virologist and wildlife veterinarian at Colorado State University who was lead author on the study, and has also published research on the risks of SARS-CoV-2 spillback using laboratory experiments with the North American deer mouse (Peromyscus maniculatus). “It brings into question which cross-species transmission events we may be missing, and what this might mean not only for public health, but for the health and conservation of the species being infected.”
Disease spillback has recently attracted substantial attention due to the spread of SARS-CoV-2, the virus that causes COVID-19, in wild white-tailed deer in the United States and Canada. Some data suggest that deer have given the virus back to humans in at least one case, and many scientists have expressed broader concerns that new animal reservoirs might give the virus extra chances to evolve new variants.

Anti-fibrotic therapy remains an unmet medical need in human chronic liver diseases. A research team led by Professor Norifumi Kawada, Osaka City University (OCU), reported the anti-fibrotic function of globin family members in hepatic stellate cells (HSCs), the main cell type involved in liver fibrosis. In mice with advanced liver fibrosis, myoglobin (MB), (neuroglobin) NGB and (cytoglobin) CYGB injection can suppress liver inflammation and fibrosis.
The functions of globin family members have been extensively studied, focusing primarily on the specific tissues in which these proteins are expressed: hemoglobin (HB) in erythrocytes, MB in muscle cells, NGB in nervous tissues, and CYGB in pericytes and fibroblasts. Beyond the well-established oxygen-binding respiratory functions of heme-containing proteins, all globins are also known to be involved in the regulation of harmful reactive oxygen species (ROS), protecting cells from oxidative stress.
“Liver fibrosis occurs after repetitive and long-lasting injury or inflammation in the liver. These injuries are accompanied with the accumulation of ROS that activate HSCs, followed by collagen production,” explains Dr. Kawada.
Along with Dr. Le Thi Thanh Thuy, PhD fellow Vu Ngoc Hieu, and colleagues, Dr. Kawada observed that when they culture human HSCs under globin treatments, MB, NGB, and CYGB enter the cellular organelles, hunt the intracellular harmful ROSs, and reduce the direct signal regulating the production of collagen. “Results showed the antioxidant capacity of the globins to be greater than the well-documented glutathione and even vitamin C,” continues Dr. Kawada.
This is great news for three members of the globin family, but what happened to HB? “We noticed that hemoglobin did not enter the cell,” explains Dr. Thuy, “we speculate this is due to size as HB is 4 times the size of its monomer siblings.”
In the next set of experiments, Dr. Kawada and his group generated a mouse model of advanced liver fibrosis using chemical agents and applied MB, NGB, and CYGB by intravenous injection. Interestingly, the therapeutic protein dramatically suppressed liver inflammation and fibrosis without any side effects. PhD fellow Hieu points out, “in addition to the liver, we focused on possible side effects with the neighboring kidney. Creatinine levels remained normal throughout the treatment.”
With this discovery, that was published in the journal Redox Biology, the research team hopes to establish a foothold to a potential therapy for liver fibrosis in the near future.