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.

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Precision Oncology: Gene Changes Predict Immunotherapy Response

Cancer Immunotherapy

Caption: Adapted from scanning electron micrograph of cytotoxic T cells (red) attacking a cancer cell (white).
Credits: Rita Elena Serda, Baylor College of Medicine; Jill George, NIH

There’s been tremendous excitement in the cancer community recently about the life-saving potential of immunotherapy. In this treatment strategy, a patient’s own immune system is enlisted to control and, in some cases, even cure the cancer. But despite many dramatic stories of response, immunotherapy doesn’t work for everyone. A major challenge has been figuring out how to identify with greater precision which patients are most likely to benefit from this new approach, and how to use that information to develop strategies to expand immunotherapy’s potential.

A couple of years ago, I wrote about early progress on this front, highlighting a small study in which NIH-funded researchers were able to predict which people with colorectal and other types of cancer would benefit from an immunotherapy drug called pembrolizumab (Keytruda®). The key seemed to be that tumors with defects affecting the “mismatch repair” pathway were more likely to benefit. Mismatch repair is involved in fixing small glitches that occur when DNA is copied during cell division. If a tumor is deficient in mismatch repair, it contains many more DNA mutations than other tumors—and, as it turns out, immunotherapy appears to be most effective against tumors with many mutations.

Now, I’m pleased to report more promising news from that clinical trial of pembrolizumab, which was expanded to include 86 adults with 12 different types of mismatch repair-deficient cancers that had been previously treated with at least one type of standard therapy [1]. After a year of biweekly infusions, more than half of the patients had their tumors shrink by at least 30 percent—and, even better, 18 had their tumors completely disappear!

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Regenerative Medicine: Making Blood Stem Cells in the Lab

Endothelial cells becoming hematopoietic stem cells

Caption: Arrow in first panel points to an endothelial cell induced to become hematopoietic stem cell (HSC). Second and third panels show the expansion of HSCs over time.
Credit: Raphael Lis, Weill Cornell Medicine, New York, NY

Bone marrow transplants offer a way to cure leukemia, sickle cell disease, and a variety of other life-threatening blood disorders.There are two major problems, however: One is many patients don’t have a well-matched donor to provide the marrow needed to reconstitute their blood with healthy cells. Another is even with a well-matched donor, rejection or graft versus host disease can occur, and lifelong immunosuppression may be needed.

A much more powerful option would be to develop a means for every patient to serve as their own bone marrow donor. To address this challenge, researchers have been trying to develop reliable, lab-based methods for making the vital, blood-producing component of bone marrow: hematopoietic stem cells (HSCs).

Two new studies by NIH-funded research teams bring us closer to achieving this feat. In the first study, researchers developed a biochemical “recipe” to produce HSC-like cells from human induced pluripotent stem cells (iPSCs), which were derived from mature skin cells. In the second, researchers employed another approach to convert mature mouse endothelial cells, which line the inside of blood vessels, directly into self-renewing HSCs. When these HSCs were transplanted into mice, they fully reconstituted the animals’ blood systems with healthy red and white blood cells.

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Moving Toward Answers in ME/CFS

Woman in bed

Thinkstock/Katarzyna Bialasiewicz

Updated September 27, 2017: The National Institutes of Health (NIH) will award four grants to establish a coordinated scientific research effort on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The total cost of the projects for fiscal year 2017 will be over $7 million, with support from multiple NIH Institutes and Centers that are part of the Trans-NIH ME/CFS Working Group.

The grants will support the creation of a consortium made up of three Collaborative Research Centers (CRC) and a Data Management Coordinating Center (DMCC). The CRCs will each conduct independent research but will also collaborate on several projects, forming a network to help advance knowledge on ME/CFS. The data will be managed by the DMCC and will be shared among researchers within the CRCs and more broadly with the research community.


Imagine going to work or school every day, working out at the gym, spending time with family and friends—basically, living your life in a full and vigorous way. Then one day, you wake up, feeling sick. A bad cold maybe, or perhaps the flu. A few days pass, and you think it should be over—but it’s not, you still feel achy and exhausted. Now imagine that you never get better— plagued by unrelenting fatigue not relieved by sleep. Any exertion just makes you worse. You are forced to leave your job or school and are unable to participate in any of your favorite activities; some days you can’t even get out of bed. The worst part is that your doctors don’t know what is wrong and nothing seems to help.

Unfortunately, this is not fiction, but reality for at least a million Americans—who suffer from a condition that carries the unwieldy name of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a perplexing disease that biomedical research desperately needs to unravel [1]. Very little is currently known about what causes ME/CFS or its biological basis [2]. Among the many possibilities that need to be explored are problems in cellular metabolism and changes in the immune system.

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Creative Minds: Does Human Immunity Change with the Seasons?

Micaela Martinez

Micaela Martinez

It’s an inescapable conclusion from the book of Ecclesiastes that’s become part of popular culture thanks to folk legends Pete Seeger and The Byrds: “To everything (turn, turn, turn), there is a season.” That’s certainly true of viral outbreaks, from the flu-causing influenza virus peaking each year in the winter to polio outbreaks often rising in the summer. What fascinates Micaela Martinez is, while those seasonal patterns of infection have been recognized for decades, nobody really knows why they occur.

Martinez, an infectious disease ecologist at Princeton University, Princeton, NJ, thinks colder weather conditions and the tendency for humans to stay together indoors in winter surely play a role. But she also thinks an important part of the answer might be found in a place most hadn’t thought to look: seasonal changes in the human immune system. Martinez recently received an NIH Director’s 2016 Early Independence Award to explore fluctuations in the body’s biological rhythms over the course of the year and their potential influence on our health.

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