Creative Minds: Exploring the Role of Immunity in Hypertension

Meena Madhur

Meena Madhur / Credit: John Russell

If Meena Madhur is correct, people with hypertension will one day pay as much attention to their immune cell profiles as their blood pressure readings. A physician-researcher at Vanderbilt University School of Medicine, Nashville, Madhur is one of a growing number of scientists who thinks the immune system contributes to—or perhaps even triggers—hypertension, which increases the risk of stroke, heart disease, kidney disease, and other serious health problems.

About one of every three adult Americans currently have hypertension, yet a surprising number don’t know they have it and less than half have their high blood pressure under control—leading many health experts to refer to the condition as a “silent killer”[1,2]. For many folks, blood pressure control can be achieved through lifestyle changes, such as losing weight, exercising, limiting salt intake, and taking blood pressure medicines prescribed by their health-care provider. Unfortunately, such measures don’t work for everyone, and some people continue to suffer damage to their kidneys and blood vessels from poorly controlled hypertension.

Madhur wants to know whether the immune system might be playing a role, and whether this might hold some clues for developing new, more targeted ways of treating high blood pressure. To get such answers, this practicing cardiologist will use her 2016 NIH Director’s New Innovator Award to conduct sophisticated, single-cell analyses of the immune systems of people with and without hypertension. Her goal is to produce the most comprehensive catalog to date of which human immune cells might be involved in hypertension.

Continue reading

International “Big Data” Study Offers Fresh Insights into T2D

World map

Caption: This international “Big Data” study involved hundreds of researchers in 22 countries (red).

It’s estimated that about 10 percent of the world’s population either has type 2 diabetes (T2D) or will develop the disease during their lives [1]. Type 2 diabetes (formerly called “adult-onset”) happens when the body doesn’t produce or use insulin properly, causing glucose levels to rise. While diet and exercise are critical contributory factors to this potentially devastating disease, genetic factors are also important. In fact, over the last decade alone, studies have turned up more than 80 genetic regions that contribute to T2D risk, with much more still to be discovered.

Now, a major international effort, which includes work from my own NIH intramural research laboratory, has published new data that accelerate understanding of how a person’s genetic background contributes to T2D risk. The new study, reported in Nature and unprecedented in its investigative scale and scope, pulled together the largest-ever inventory of DNA sequence changes involved in T2D, and compared their distribution in people from around the world [2]. This “Big Data” strategy has already yielded important new insights into the biology underlying the disease, some of which may yield novel approaches to diabetes treatment and prevention.

Continue reading

Alzheimer’s Disease: Tau Protein Predicts Early Memory Loss

PET imaging of brains affected by Alzheimer's disease

Caption: PET scan images show distribution of tau (top panel) and beta-amyloid (bottom panel) across a brain with early Alzheimer’s disease. Red indicates highest levels of protein binding, dark blue the lowest, yellows and oranges indicate moderate binding.
Credit: Brier et al., Sci Transl Med

In people with Alzheimer’s disease, changes in the brain begin many years before the first sign of memory problems. Those changes include the gradual accumulation of beta-amyloid peptides and tau proteins, which form plaques and tangles that are considered hallmarks of the disease. While amyloid plaques have received much attention as an early indicator of disease, until very recently there hadn’t been any way during life to measure the buildup of tau protein in the brain. As a result, much less is known about the timing and distribution of tau tangles and its relationship to memory loss.

Now, in a study published in Science Translational Medicine, an NIH-supported research team has produced some of the first maps showing where tau proteins build up in the brains of people with early Alzheimer’s disease [1]. The new findings suggest that while beta-amyloid remains a reliable early sign of Alzheimer’s disease, tau may be a more informative predictor of a person’s cognitive decline and potential response to treatment.

Continue reading

Repurposing an “Old” Drug for Alzheimer’s Disease

Senator Mikulski during her tour of NCATS

Caption: Here I am with Senator Barbara Mikulski (center) and NCATS Director Chris Austin (right). Credit: NIH

Alzheimer’s disease research is among the many areas of biomedical science that Senator Barbara Mikulski has championed during her nearly 40 years on Capitol Hill. And it’s easy to understand why the Senator is concerned: an estimated 5 million Americans age 65 and older have Alzheimer’s disease, and those numbers are expected to rise exponentially as the U.S. population continues to age.

So, I was thrilled to have some encouraging progress to report last week when Senator Mikulski (D-MD) paid a visit to NIH’s National Center for Advancing Translational Sciences (NCATS) in Gaithersburg, MD. After a whirlwind tour of the cutting-edge robotics facility for high throughput screening of small molecules, she joined me and NCATS Director Dr. Chris Austin in announcing that, thanks to an innovative public-private partnership, an experimental drug originally developed to fight cancer is now showing promise against Alzheimer’s disease.

Continue reading

DNA Analysis Finds New Target for Diabetes Drugs

ATCG's with a silhouette of people

Credit: Jane Ades, National Human Genome Research Institute, NIH

Type 2 diabetes (T2D) tends to run in families, and over the last five years the application of genomic technologies has led to discovery of more than 60 specific DNA variants that contribute to risk. My own research laboratory at NIH has played a significant role in this adventure. But this approach doesn’t just provide predictions of risk; it may also provide a path to developing new ways of treating and preventing this serious, chronic disease that affects about 26 million Americans.

In an unprecedented effort aimed at finding and validating new therapeutic targets for T2D, an international team led by NIH-funded researchers recently analyzed the DNA of about 150,000 people across five different ancestry groups. Their work uncovered a set of 12 rare mutations in the SLC30A8 gene that appear to provide powerful protection against T2D, reducing risk about 65%—even in the face of obesity and other risk factors for the disease [1].

Continue reading