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The National Institutes of Health (NIH) Research Updates – November 2022

CATEGORY
Scientific Staffing

DATE
November 1, 2022

The National Institutes of Health (NIH) is our nation’s medical research agency. Its mission focuses on scientific discoveries that improve health and save lives. Founded in 1870, the NIH conducts scientific research through its Intramural Research Program (IRP). It supports approximately 1,200 principal investigators and more than 4,000 postdoctoral fellows conducting basic, translational, and clinical research. In this blog, we will highlight recent innovative NIH research.

Recent Research by The National Institutes of Health

Simple Blood Test May Thwart a Complicated Cancer

The liver helps our bodies metabolize food, break down toxins, and produce essential proteins and enzymes. However, when cancerous cells develop within the liver, they can cause an overproduction of these substances, leading to a build-up in the blood and severe health problems. Often, these conditions go unnoticed until the disease has progressed to a more advanced stage, where treatment options are limited.

A study by senior IRP investigator Dr. Xin Wei Wang and his NIH research team has found a simple blood test that can predict cancer risk.

“The technology is getting better and better, allowing us to detect a tumor as small as one or two centimeters,” Dr. Wang says, “but even at this size, some tumors are already pretty aggressive. We think the cancer may actually occur years before symptoms or visible tumors appear.”

The most frequent type of liver cancer, hepatocellular carcinoma (HCC), is usually caused by hepatitis B and C. However, not all people infected with the viruses develop HCC. This may be due to how their body’s immune system responds to viruses. Dr. Wang and his team believed that variations in immunity might produce diagnosable biomarkers showing a person’s likelihood of developing cancer.

The researchers used a new technology called VirScan to compare blood samples from

899 individuals enrolled in a long-term study of liver cancer conducted by the National Cancer Institute (NCI) and the University of Maryland against 1,000 viral strains in the library. The researchers found that people who had previously contracted viruses (other than hepatitis B and C) were more likely to develop HCC. They also created a blood test that can measure an individual’s risk of developing HCC based on the presence of antibodies.

Based on their findings, the team believes their blood test can identify high-risk HCC patients seven years before diagnosis. If the researchers’ findings are correct, doctors may someday use this test to determine which patients need to be monitored closely for HCC. Catching it early would enable treatment to begin as soon as the disease appears.

Although the sample size in the study was small, Dr. Wang says the results are encouraging, and his team plans to test the novel blood test in 6,000 people for liver cancer diagnosis prospects.

“I was surprised,” Dr. Wang said of the positive results. “We were able to identify many of the viral features that actually show an association with HCC and compare them to those not related to liver cancer. This was very exciting, because we didn’t really expect it.”

Taming Unruly Stem Cells to Enhance Eye Research

New IRP research could make it easier to grow organoids that Mimic the eye’s retina. Scientists have relied upon flat collections of a single cell type for their experiments up until now, but these three-dimensional structures more closely resemble reality. They have distinct layers containing all the major cell types found in human retinas. This study can accelerate discoveries about many vision-impairing diseases, such as macular degeneration.

“A retinal organoid is as close to being a retina in a dish as we’ve ever had,” says IRP senior investigator Tiansen Li, Ph.D., the new study’s senior author.

Scientists can create an unlimited number of cell lines with specific properties by taking skin or blood cells from a patient and turning them into induced pluripotent stem cells (iPSCs). These cell lines allow researchers to investigate the root cause of a person’s vision problem by growing retinal organoids with the same genetic mutations as the patient.

In the new study, Dr. Li’s team added nicotinamide (a form of vitamin B3) to their process for turning iPSCs into retinal organoids to study its effects. Nicotinamide has previously been used to encourage iPSCs to develop into the retinal pigment epithelium (RPE).

The IRP researchers exposed stem cells from eight different cell lines to nicotinamide for either eight or twenty-one days. They found that treating stem cells with nicotinamide for eight days significantly increased the yield of retinal organoids from all cell lines, including those that produced very few organoids without nicotinamide. The three-week treatment also yielded more promising results for some cell lines but decreased for one.

“During development, cells are influenced by their intrinsic programs, obviously, but also by external environmental cues,” Dr. Li explains. “These cues act at defined time points, so a cue that does one thing at one point in time, two days later might do the opposite. That applies to nicotinamide as well. If you apply it for an extended duration, it might overstay its welcome.”

The study also explained how nicotinamide encourages iPSCs to develop into retinal organoids. In the early stages, stem cells treated with the drug quickly transformed into an immature neural cell form that could potentially become a retinal cell.

Nicotinamide is a popular and affordable drug that has the potential to become a standard part of labs’ procedures for producing retinal organoids. When scientists use it to facilitate the creation from stem cell lines, they could find it much easier to make discoveries about many diseases affecting vision because more organoids would be successfully created.

“We continue to gather data to support the validity of this approach, and our hope and expectation is that the entire field will adopt it, just as they adopted other standardized and widely used additions to retinal organoid production,” Dr. Li says. “I would like to see it used in everybody’s procedures in the next few years. That would make me very happy.”

Hair straightening chemicals associated with higher uterine cancer risk

3% of all new cancer cases are uterine cancer, making it the most common type of female reproductive system cancer. In 2022, there will be an estimated 65,950 new cases of uterine cancer. According to a recent study by researchers at the National Institutes of Health (NIH), women who use chemical hair straightening products have a higher risk of developing uterine cancer than women who do not report using these products.

The study drew data from 33,497 U.S. women ages 35-74 who participated in the Sister Study conducted by the National Institute of Environmental Health Sciences (NIEHS), part of NIH, to identify risk factors for developing breast cancer and other health conditions. The study followed the women for over a decade, during which 378 were diagnosed with uterine cancer.

The researchers discovered that women who frequently used hair straightening products were more than twice as likely to develop uterine cancer in the future compared to those who didn’t use them.

“We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%,” said Alexandra White, Ph.D., head of the NIEHS Environment and Cancer Epidemiology group and lead author on the new study. “This doubling rate is concerning. However, it is important to put this information into context – uterine cancer is a relatively rare type of cancer.”

The study found that approximately 60% of self-identified Black women reported using straighteners in the previous year. Although no relationship was found between straightener use and uterine cancer incidence by race, adverse health effects may be more common for Black women due to the higher prevalence of use.

“Because Black women use hair straightening or relaxer products more frequently and tend to initiate use at earlier ages than other races and ethnicities, these findings may be even more relevant for them,” said Che-Jung Chang, Ph.D., an author of the new study and a research fellow in the NIEHS Epidemiology Branch.

Hair products that contain chemicals, specifically straighteners, could be more dangerous than other personal care items because they are absorbed through the scalp. Additionally, burns and lesions caused by straighteners may further increase the absorption of these chemicals.

3D map reveals DNA organization within human retina cells

The genome topology of the human retina has been largely uncharacterized. Scientists at the National Eye Institution (NEI) have created a high-resolution map of chromatin interactions in the human retina, using Hi-C, a tool used to study 3D genome organization.

Chromatin fibers are structures that package 3 billion nucleotide-long DNA molecules into compact structures that fit into chromosomes within each cell’s nucleus. By understanding this comprehensive gene regulatory network, researchers can gain insights into the regulation of gene expression in general, and in retinal function, in both rare and common eye diseases.

“This is the first detailed integration of retinal regulatory genome topology with genetic variants associated with age-related macular degeneration (AMD) and glaucoma, two leading causes of vision loss and blindness,” said the study’s lead investigator, Anand Swaroop, Ph.D., senior investigator and chief of the Neurobiology Neurodegeneration and Repair Laboratory at the NEI, part of the National Institutes of Health.

By studying the chromatin topology map in combination with data on retinal genes and regulatory elements, they found patterns of interaction at retinal genes that suggest how 3D chromosome organization plays a vital role in regulating genes specific to certain tissues. They also found that 35.7% of gene pairs interact through a chromatin loop in humans and mice.

“Having such a high-resolution picture of genomic architecture will continue to provide insights into the genetic control of tissue-specific functions,” Swaroop said.

By combining the chromatin topology map with data on genetic variants, researchers could pinpoint specific genes that are likely causal in diseases like AMD and glaucoma, which are leading causes of vision loss and blindness. The integrated genome regulatory map will also assist in evaluating genes associated with other common retina-associated diseases.

Findings Suggest COVID-19 Rebound Not Caused by Impaired Immune Response

A study published in Clinical Infectious Diseases recently found that it is unlikely weakened immune responses cause COVID-19 rebound. The study, led by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), aimed to understand better the characteristics of COVID-19 rebound in patients that had taken nirmatrelvir/ritonavir (Paxlovid), an antiviral therapeutic developed by Pfizer, Inc. and how SARS-CoV-2 affects white blood cells.

The Centers for Disease Control and Prevention (CDC) defines a COVID-19 rebound as either a return of symptoms or a new positive viral test result after having tested negative. The study selected 8 adult patients enrolled in an ongoing COVID-19 study at the NIH Clinical Center in Bethesda, Maryland, and other local hospitals. All patients in the study had been vaccinated and boosted for COVID-19 and did not experience any serious illness that required hospitalization after getting the initial or rebound infection.

Researchers found no evidence that genetically mutated strains of SARS-CoV-2 caused participants to experience COVID-19 rebound after taking Paxlovid. Also, no evidence suggests that these individuals had delayed development of antibodies. The researchers found that robust SARS-CoV-2 T-cell responses were present in rebound patients. It was determined that, on average, the level of T-cell response was more significant in rebound patients than in early acute COVID-19 patients. The latter did not experience a rebound effect. Out of the eight participants, only one rebound patient had infectious SARS-CoV-2 detected by viral culture.

The findings suggest that the robust cellular immune response could partially drive residual viral RNA throughout the respiratory tract rather than an impaired immune response allowing viral replication. The current data strongly suggests that patients who experience symptom relapse should be isolated, and those with weakened immune systems should be given extended courses of Paxlovid. The authors also noted that further studies must be conducted to understand the clinical significance and far-reaching effects of COVID-19 rebound.