Snapshots of Life: Fighting Urinary Tract Infections

Urinary tract infection in a mouse

Source: Valerie O’Brien, Matthew Joens, Scott J. Hultgren, James A.J. Fitzpatrick, Washington University, St. Louis

For patients who’ve succeeded in knocking out a bad urinary tract infection (UTI) with antibiotic treatment, it’s frustrating to have that uncomfortable burning sensation flare back up. Researchers are hopeful that this striking work of science and art can help them better understand why severe UTIs leave people at greater risk of subsequent infection, as well as find ways to stop the vicious cycle.

Here you see the bladder (blue) of a laboratory mouse that was re-infected 24 hours earlier with the bacterium Escherichia coli (pink), a common cause of UTIs. White blood cells (yellow) reach out with what appear to be stringy extracellular traps to immobilize and kill the bacteria.

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Creative Minds: Complex Solutions to Inflammation

Hao Wu

Hao Wu

For nearly 20 years, Hao Wu has studied innate immunity, our body’s first line of defense against infection. One of her research specialties is the challenging technique of X-ray crystallography, which she uses to capture the atomic structure of key molecules that drive an inflammatory response. But for this method to work, the proteins have to be coaxed to form regular crystals—and that has often proven to be prohibitively difficult. Wu, now at Boston Children’s Hospital and Harvard Medical School, can be relentless in her attempts to crystallize difficult molecular structures, and this quality has helped her make a number of important discoveries. Among them is the seminal finding that innate immune cells process and internalize signals to handle invading microbes much differently than previously thought.

Innate immune cells, which include macrophages and neutrophils, patrol the body non-specifically, keeping a look out for signs of anything unusual. Using protein receptors displayed on their surfaces, these cells can sense distinctive molecular patterns on microbes, prompting an immediate response at the site of infection.

Wu has shown that these cells form previously unknown protein complexes that mediate the immune response [1, 2]. She received an NIH Director’s 2015 Pioneer Award to help translate her expertise in the structural biology of these signaling complexes into the design of new kinds of anti-inflammatory treatments. This award helps exceptionally creative scientists to pioneer transformative approaches to major challenges in biomedical and behavioral research.

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Precision Medicine: Who Benefits from Aspirin to Prevent Colorectal Cancer?

Aspirin and DNA StethoscopeIn recent years, scientific evidence has begun to accumulate that indicates taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) on a daily basis may lower the risk of developing colorectal cancer. Now, a new study provides more precise information on who might benefit from this particular prevention strategy, as well as who might not.

Published in the journal JAMA, the latest work shows that, for the majority of people studied, regular use of aspirin or NSAIDs was associated with about a one-third lower risk of developing colorectal cancer. But the international research team, partly funded by NIH, also found that not all regular users of aspirin/NSAIDs reaped such benefits—about 9 percent experienced no reduction in colorectal cancer risk and 4 percent actually appeared to have an increased risk [1]. Was this just coincidence, or might there be a biological explanation?

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Rare Disease Sleuths Uncover New Clues to Stroke

Drawing of a brain section with an inflamed blood vessel

Caption: A variation in the gene that codes for a key blood vessel enzyme makes children prone to fevers, rash, and strokes.
Credit: Jonathan Bailey, National Human Genome Research Institute, NIH

A medical mystery that began when a 3-year-old girl came to the NIH Clinical Center here in Bethesda, MD, a decade ago has just been solved. The findings not only promise to help children suffering from a devastating rare disease, but to advance our overall understanding of stroke and other blood vessel disorders.

When researchers first met the little girl, they were baffled. She had a most unusual—and unexplained—constellation of symptoms: recurring fevers, rashes, and strokes, which, sadly, had left her severely disabled. Researchers thought the cause probably wasn’t genetic, because none of the girl’s family members were affected, plus they hadn’t seen other children with similar problems. While they searched for clues, they treated the girl with immunosuppressive drugs to reduce blood vessel inflammation and thereby lower the chance of future strokes.

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NIH Research Leads to New Rheumatoid Arthritis Drug

x-ray image of hands

X-ray image of the hands of a patient with rheumatoid arthritis. Note that the joints at the base of the fingers are eroded — and some, like the index finger on both hands, are actually dislocated.
Copyright (2012) American College of Rheumatology.

About 1.5 million [1] people in the US suffer from rheumatoid arthritis (RA). It is a chronic illness in which the immune system, which protects us from viral and bacterial invaders, turns on our own body and viciously attacks the membranes that line our joints. The consequences can be excruciating: pain, swelling, stiffness, and decreased mobility.  Over time, the joints can become permanently contorted, as in this X-ray image.

There are several RA medications on the market, but I want to tell you about a new one called tofacitinib, a pill which the FDA approved late last year [2]. The drug works by targeting a protein called Janus kinase 3, which was discovered by John O’Shea and colleagues here at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 20 years ago [3]. As I mentioned in a previous post it takes a really long time to go from a basic discovery to a drug—in most cases nearly 15 years. This drug has been even longer in the making! Shortly after discovering Janus kinase 3 in 1993, NIAMS researchers also revealed its role in inflammation, leading to a public-private collaboration with Pfizer that has now culminated in the approval of tofacitinib.

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