IRP Discoveries

Drilling Down Into DNA and Disease

Catching Up With Former NIH Director Francis Collins

DNA

It has been 20 years since researchers around the world successfully mapped most of the roughly 20,000 genes that make up the human genome. Former NIH Director Francis Collins, M.D., Ph.D. led the Human Genome Project through most of its 13-year progression and continues to push the limits of genetics today. As we celebrate National DNA Day on April 25, the 71st anniversary of the publication of DNA’s double-helix structure, we took some time to catch up with Dr. Collins and learn what he’s been up to since he stepped down as NIH Director in December 2021.

The dozen or so researchers in Dr. Collins’s lab focus on the role of genes in a variety of diseases, ranging from conditions caused by rare mutations in single genes to common ailments influenced by the interplay of hundreds of genes, lifestyle behaviors, and environmental factors. His two main research interests are type 2 diabetes and Hutchinson-Gilford progeria syndrome, a rare disorder that causes exceptionally rapid aging in children.

Double Trouble for Alcohol-Associated Liver Disease

IRP Researchers Identify Two Types of Liver Damage and a Possible Treatment for One

fatty liver

While alcohol is a source of celebration and relaxation for many, it does come with significant drawbacks, especially when people over-consume it. For people who have trouble controlling their alcohol consumption — a condition called alcohol use disorder (AUD) — one of the most dangerous consequences can be damage to the liver, the organ that filters toxins like alcohol out of the blood.

In honor of Alcohol Awareness Month this April, I spoke with IRP senior investigator Bin Gao, M.D., Ph.D., about his quest to understand how AUD damages the liver and other organs by uncovering the molecules and mechanisms involved in that damage. His IRP lab also investigates how alcohol is processed in the body, producing insights that could be used to identify strategies for reducing alcohol consumption or reversing alcohol’s harmful effects.

Saving the Skin From a Renegade Immune Reaction

IRP Study Provides Insight into Cancer Treatment’s Skin-Thickening Side Effects

person massaging his hands

Scientists have long dreamt of leveraging information about our genes to personalize medical treatment. However, in working towards that effort, they have increasingly discovered the importance not just of what genetic variants are present in a person’s DNA, but how active each of those genes is. Now, new IRP research suggests the possibility of using that information to personalize medical treatment for patients who experience serious skin problems after receiving a transplant of the bone marrow’s blood-producing stem cells.

Gender Differences in Emotional Responses May Start in the Womb

Research Suggests Hormonal Exposures In-Utero Influence Mental Health

illustration of connections in the brains of a man and a woman

Over the past few decades, broad stereotypes about how men and women behave have given way to a more nuanced understanding of the many factors that contribute to sex differences. While culture and environment undoubtedly play a huge role, it’s becoming increasingly clear that biological influences shape male and female brains differently starting at the very beginning of life. Recent IRP research sheds additional light on this age-old question by revealing that women exposed to higher levels of certain hormones in-utero had emotional responses to the stresses of the COVID-19 pandemic that more closely matched those of men.

Breaking Down the Meat We Eat

IRP Research Explores the Health Effects of Specific Dietary Components

examining a raw steak with a magnifying glass

When Hippocrates said, “Let food by thy medicine and medicine thy food,” he was on to something. That’s why National Nutrition Month, celebrated every March, calls attention to the important link between health and diet. To commemorate Nutrition Month this year, we spoke with IRP senior investigator Rashmi Sinha, Ph.D., about her efforts to tease out not only which foods help or harm out bodies, but why they do so.

Determining the health effects of different foods has long been a holy grail in research, but with so many variables, our knowledge remains vague at best. Some foods — processed meats, certain fats, sugar — clearly have negative effects when eaten in large amounts, while others like green vegetables and legumes are helpful. Unfortunately, there are a lot of unknowns in between.

From Fruit Fly Genes to Sweet Dreams

IRP’s Susan Harbison Unravels the Genetics of Sleep Disorders

swarm of fruit flies on an apple

Comedian George Carlin used to call sleep “a bizarre activity.” In his act, he observed, “For the next several hours, while the sun is gone, I’m going to become unconscious, temporarily losing command over everything I know and understand. When the sun comes up, I’ll resume my life.”

Every year on March 15, the celebration of World Sleep Day reminds us that sleep remains a baffling biological mystery. What happens when we sleep, why we need it, and why it varies so much between individuals are still unclear despite the best efforts of many scientists. That enduring enigma is what has driven IRP senior investigator Susan Harbison, Ph.D., to investigate the biological basis and genetics of sleep.

Experimental Antibody Tightens Up Leaky Blood Vessels

Treatment Could Benefit Patients With a Variety of Illnesses

blood vessels

Our blood is a miraculous mix of cells and critical fluids that keep our organs running and fight off dangerous infections. Of course, for blood to do its job, it has to stay in our veins and arteries, which is easier said than done for people with certain illnesses. Fortunately, a recent IRP study has demonstrated the promise of a potential new treatment for people with dangerously leaky blood vessels.

Several life-threatening conditions, including Ebola and sepsis due to an uncontrolled infection, cause the fluid component of blood to leak out of blood vessels. IRP senior investigator Kirk Druey, M.D., however, came to study the phenomenon through a very rare ailment called Clarkson disease, which causes patients to periodically experience ‘flares’ or ‘episodes’ when their veins and arteries suddenly and inexplicably start leaking.

Applying Rare Disease Discoveries to Diabetes

Patients With Rare Metabolic Conditions Yield Insights Into Common Ailments

overweight patient talking with doctor

Young doctors are taught the adage, “When you hear hoofbeats, think horses, not zebras.” Just as you would not expect to find a zebra in your barn, when making a diagnosis, you generally don’t expect to find an unusual disease. However, just as there are still zebras in the world, there are also rare diseases. On Rare Disease Day, celebrated on the last day of February each year, we call attention to the 300 million people affected by them.

Defined as conditions that affect fewer than 1 in 2,000 people, rare diseases pose both challenges and opportunities to medical research. Because they are so uncommon, diagnosis can take years, and treatments may be difficult to obtain or may not yet exist. However, for IRP Lasker Clinical Research Scholar Rebecca J. Brown, M.D., M.H.Sc., the study of several rare metabolic diseases may shed light on the causes of one of the most common diseases in the U.S.

The Heartache of Discrimination

Allana T. Forde Unpacks Racial Disparities in Heart Health

black man having chest pains

Discrimination comes in many forms, and people experience it and cope with it in different ways. The accumulation of stress arising from discrimination can lead to wear and tear on the body in a process called ‘weathering’, which ultimately harms cardiovascular health. This is one of the key reasons Black Americans have a higher rate of cardiovascular disease than all other racial and ethnic groups in the U.S. and are much more likely to die from cardiovascular conditions than other racial and ethnic groups.

NIH Stadtman Investigator Allana T. Forde, Ph.D., M.P.H., hopes to reduce these startling health disparities by examining how psychosocial stressors, including discrimination, affect the cardiovascular health of subgroups of the Black population, including Afro-Caribbean, Afro-Latino, and African American individuals. She also endeavors to identify the protective and adaptive factors that impact the relationship between discrimination and cardiovascular health. In honor of American Heart Month, I spoke with Dr. Forde about her research on discrimination and cardiovascular health in Black Americans, as well as how her research might improve cardiovascular health and inform cardiovascular disease prevention strategies.

Alternative Therapy Relieves Immunotherapy’s Neurological Consequences

Case Studies Highlight New Way to Treat Common Side Effect

child with cancer

New medical treatments nearly always come packaged with new side effects. CAR-T cell therapy, a game-changing ‘immunotherapy’ for cancer, is no exception. However, a set of case studies reported by IRP researchers could help physicians better contend with one of the therapy’s most worrisome complications.

CAR-T cell therapy involves collecting immune cells called T cells from a patient's blood, genetically modifying them to turn them into cancer killers, growing millions of the modified cells in the lab, and then returning the cancer-seeking missiles to the patient’s body. As promising as the approach is for eliminating cancer, the first CAR-T cell therapy was approved by the U.S. Food and Drug Administration (FDA) only a bit more than six years ago, so clinicians are still figuring out the best ways to manage its less desirable effects.