rare diseases

Unlocking the Genetic Mysteries of Rare Autoinflammatory Diseases

IRP Researcher Finds Explanations and Hope

child getting her cheek swabbed for DNA analysis

Rare Disease Day, celebrated on or near February 29 — the rarest day on the calendar — calls attention to the 300 million people in the world who have some sort of rare disease. For children born with one of those diseases, speedy diagnosis and treatment may be necessary to ward off long-term complications, but that’s much easier said than done. This is especially true for pediatric autoinflammatory diseases, in which the immune system attacks the child’s own body. IRP senior investigator Raphaela T. Goldbach-Mansky, M.D., M.H.S., has made it her mission to discover and define these diseases and the genes that cause them, and then find a way to provide treatment. 

Rooting Out Genetic Risks for Gum Disease

IRP’s Oral Health Experts Explore Why It’s Not Always About Brushing and Flossing

illustration of inflammation in the gums

When you dig into that bowl of candy this Halloween, you may want to keep in mind that those sweets are not only fueling your sweet tooth, but also an army of creepy crawlies living in your mouth, busily forming a sticky film of plaque and attacking your gums.

As Dental Hygiene Month comes to a close this October, we spoke with IRP Clinical Research Specialist Laurie Brenchley, R.D.H., a dental hygienist and clinical study coordinator in the laboratory of IRP senior investigator Niki Moutsopoulos, D.D.S., Ph.D. Together, Brenchley and Dr. Moutsopoulos are studying the link between oral health and the immune system, with a specific focus on cases in which genetic factors increase susceptibility to severe gum disease, more formally known as periodontitis.

NIH Book Talk Highlights IRP Cancer Research

"A Fatal Inheritance" Author Larry Ingrassia Discusses His New Book

Lawrence Ingrassia at the NIH event

In June 2024, Mr. Lawrence Ingrassia visited NIH to give a talk about his book, A Fatal Inheritance: How a Family Misfortune Revealed a Medical Mystery, which evolved from interviews with current and former IRP researchers, including IRP scientist emeritus Joseph F. Fraumeni, Jr., M.D.

Li-Fraumeni Syndrome (LFS) is an inherited disorder caused by deleterious variants in the TP53 tumor-suppressor gene that lead to very elevated risk of cancers, including sarcomas, brain, breast, and many others. Investigators at NIH have followed families with LFS since the syndrome was first described in 1969 by Dr. Fraumeni and his late collaborator, Dr. Frederick P. Li. Drs. Li and Fraumeni’s seminal discovery was the foundation on which studies of genetic susceptibility to cancer were built.

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.

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.

Fighting the Fungus Among Us

Overactive Immune Response Sets Stage for Infection

various fungi growing in a petri dish

Fungal infections are a serious medical threat to many people, especially those who are critically ill or have weakened immune systems. What’s more, outbreaks are on the rise, as studies show that rising global temperatures are causing fungi to evolve into new strains and grow in regions that were once too cold for comfort. Recent outbreaks include a tragic incident at a Michigan paper mill that sickened nearly 100 people and caused one death, as well as a cluster of fungal infections that have killed at least seven women who underwent cosmetic surgery at clinics in Mexico.

Commemorating Fungal Disease Awareness Week this week brings attention to the importance of combating fungal threats to our well-being. The theme this year is ‘Think Fungus,’ and that’s exactly what IRP senior investigator Michail Lionakis, M.D., Sc.D., has been doing for the last 20 years.

Crucial Protein Reins in Overzealous Bone Growth

IRP Study Answers Key Questions About Bone Development and Healing

man with fractured foot

The idea that there can be “too much of a good thing” applies just as much to the human body as it does to an overly sweet dessert or excessive holiday decorations. For instance, you might think that rapid bone growth would be helpful for fixing fractures, but it can actually make bones weaker in the long run. A recent IRP study revealed how a certain molecule manages the way bones develop in a growing fetus and heal after damage to make sure they don’t trade strength for speed.

Talk Science to Me

IRP Researchers Leave Jargon Behind for Three-Minute Talks Competition

scientist speaking into a megaphone

Scientific research is often said to take place in an “ivory tower” — not exactly an image associated with accessibility, trust, or empathy. Yet it is essential that members of the public be able to understand the work that researchers devote their lives to.

In recognition of that need, dozens of IRP postbacs, graduate students, and postdocs participate each year in NIH’s Three Minute Talks (TmT) competition. On June 22, this year’s eleven finalists offered clear and concise descriptions of their efforts to unfold the mysteries of proteins’ shapes, discover the lethal role of inflammation in infections, repackage cancer therapies to enhance their effectiveness, and much more.

Treatment Corrects Consequences of Accelerated Cellular Aging

Mouse Study Demonstrates Promise of New Therapy for Rare Genetic Conditions

time warp

If you ask a scientist how old you are, you may be surprised to get a different answer depending on who you’re talking to. That’s because age can be measured both ‘chronologically’ — in terms of time — and at a cellular level. Indeed, certain genetic mutations cause cells to age faster, leading to a host of health problems. Fortunately, a recent IRP study performed in mice suggests that boosting levels of a specific molecule could help alleviate some of those patients’ symptoms.