Jefferson Investigates: Small RNAs and Tuberculosis; How ALS Develops; Stigma of Hepatitis B
Exploring short noncoding RNAs as targets for tuberculosis, the pathogenesis of ALS, and how stigma affects outcomes of Asian Americans with hepatitis B.
Image Credit: © Adobe Stock NanSan/801196124
How Stigma Affects Asian Americans Living with Hepatitis B
Asian Americans comprise just 6% of the U.S. population, but they represent over 60% of Americans with hepatitis B. Hepatitis B (HBV) is a virus that infects the liver, and while some people may recover from the infection, others can go on to develop liver failure or cancer. HBV is transmitted through blood, semen or other bodily fluids, but it can also be passed from mother to child during birth, which is how the majority of Asian Americans acquire the disease.
Up until 2010, laws in China allowed for discrimination against people with HBV, barring adults from employment and keeping children out of school. Though these policies are now outlawed, there remains a stigma against the disease in both China and the U.S.
Researcher Hee-Soon Juon, MSN, PhD at Thomas Jefferson University has been working with Asian-American communities to investigate and raise awareness of HBV since the early 2000’s. In a new study published in The Journal of Viral Hepatitis, she explores how stigma against HBV affects those with the condition.
The study surveyed 365 Korean-Americans with chronic hepatitis B (CHB) to see how stigma against HBV affected them. Participants responded to questions about their physical health, mental health and if they believed they had experienced racial discrimination.
Dr. Juon found that people who felt more stigmatized were more likely to report worse depression and physical health, and that greater knowledge of the disease didn’t necessarily translate to feeling less judged for their condition. Perceived racial discrimination was also tied to feelings of stigma and depression.
“We confirmed that stigma is very impactful for a CHB patient,” says Dr. Juon. “This can have consequences on their treatment journey.”
In fact, past research has shown that stigma against a disease may dissuade individuals from seeking care, cause mental distress or lead to explicit discrimination. Dr. Juon says the next steps in this research will be developing interventions that can help combat stigma for those with HBV.
By Marilyn Perkins
Image Credit: © Adobe Stock Thippaphone/761182778
Small RNAs Boost Immune Response to Tuberculosis
Tuberculosis kills about 1.3 million people each year, making it one of the most lethal infectious diseases in the world. Now, molecular biologist Yohei Kirino, PhD and his research team at Thomas Jefferson University has found that certain RNA molecules in people with tuberculosis are drastically different than those in healthy people. The findings, published in the journal Molecular Therapy Nucleic Acids, reveal a potential pathway to bolster the immune system against infection.
Small RNA molecules known as short noncoding RNAs show up in the body in response to an infection. Sequencing RNA from a blood sample is one way to find out what kind and how much of different RNA molecules are present. “However, our previous research showed that there are abundant amounts of short noncoding RNAs in infected cells that standard RNA sequencing is not catching,” says Dr. Kirino.
In a study spearheaded by PhD student Justin Gumas, the researchers modified the typical way to sequence RNA. Standard sequencing methods rely on two chemical features on the ends of RNA molecules that many short noncoding RNAs do not have. So, the researchers first treated the samples with an enzyme that equipped every RNA molecule with these features. They were then able to sequence all of the short noncoding RNAs in people with tuberculosis and compare them with those in healthy people.
The team found many short noncoding RNAs that had not been sequenced before and many that activate the immune system. The findings not only reveal how small noncoding RNAs drive the immune system to respond to infection like tuberculosis, but also provide a pool of potential therapeutic targets and biomarkers for estimating the severity of the immune response.
“During an infection, we think these small noncoding RNAs work as an immune booster,” says Dr. Kirino. “We believe there is an RNA pathway in the body that kick starts the immune response to tuberculosis infection.”
By Roni Dengler
Image Credit: © Adobe Stock Sorin/87082202
New Insights into the Pathogenesis of Amyotrophic Lateral Sclerosis
The symptoms of amyotrophic lateral sclerosis (ALS) — a neurodegenerative disease that involves loss of nerve cells that control movement — tend to emerge in adulthood. To Davide Trotti, PhD, a neuroscientist at Thomas Jefferson University, this suggests that some unknown trigger causes a shift from a quiescent state to a biochemical storm causing neuronal death.
One hypothesized trigger is dysfunction of energy pathways in the central nervous system. The metabolism of glucose in the brain is altered in people with a specific ALS-linked genetic mutation, called C9-NRE, and this change occurs many years before the onset of muscle weakening that characterizes the disease.
Dr. Trotti and his collaborators embarked on molecular detective work to describe how altered energy metabolism is linked to neuronal dysfunction. In a new paper, published in EMBO Reports, the team showed how altered glucose metabolism in the brain and spinal cord are damaging to motor neurons in preclinical models that carry the genetic C9-NRE mutation. Neuronal dysfunction, in turn, further undermines energy pathways in a vicious cycle of stress responses. This feedforward loop of troubles that the researchers observed in cell culture and in animal models likely play a role in the neurodegeneration seen in ALS patients.
In carefully teasing out the molecular pathways involved, Dr. Trotti says he hopes to identify potential therapeutic targets whereby a drug might interrupt the chain reaction. The idea is to prevent the triggering event and hopefully stave off or slow down disease progression in patients with the genetic mutation.
“There are drugs on the market that can affect these processes,” he says, “and they are already FDA approved.” Dr. Trotti has hope for medications that are prescribed for diabetes, a condition that also involves altered glucose metabolism. Testing such drugs in preclinical models is the next step to see if they correct the metabolic imbalance.
By Jill Adams
