Seeking the genetic underpinnings of lupus

January 31, 2014 by Jacqueline Mitchell, Tufts University
Elisabeth Adkins is the first student to take advantage of the mammalian genetics “Jax track,” a joint program of the Sackler School and the Jackson Laboratory in Maine. Credit: Alonso Nichols

Lupus is one of the most enigmatic of diseases. It can take years to diagnose, marked as it is by a laundry list of seemingly unrelated symptoms: fever, fatigue, rashes, hair loss, sensitivity to light, seizures and even psychosis. Nearly 2 million Americans have some form of lupus, an autoimmune disorder, that is, one in which the immune system wages war on the body's own cells and tissues. More than 90 percent of those who suffer from it are women—and there is no cure.

Elisabeth Adkins, a doctoral student at the Sackler School, is trying to decode the genetic underpinnings of the disease, a crucial step in combatting it. She's working in the lab of Derry C. Roopenian, a clinical professor at Tufts School of Medicine and a professor at the Jackson Laboratory, and is the first student to take advantage of the mammalian genetics "Jax track," a joint program of the Sackler School and the Jackson Laboratory, an independent genetics research organization based in Bar Harbor, Maine. The program, launched in 2011, offers students in Tufts' genetics program—which emphasizes human disease—in-depth training in mammalian genetics, an increasingly recognized need in biomedical research.

Established as a cancer research center in 1929, the Jackson Lab is famous for its . It maintains a "library" of special strains of mice that make it easy to study certain diseases in humans. The type of mice that Adkins and Roopenian use arose accidentally, through mutation; they begin to exhibit lupus-like symptoms by the time they are four weeks old. It's a lesser-known strain of mice, but a potentially promising one. "We think it's one of the better models," says Adkins, who received a 2013 Gina M. Finzi Memorial Student Summer Fellowship from the Lupus Foundation to support her research. "We see a lot of the same indicators [in these mice] that human lupus patients have."

One such indicator is kidney failure, something that human often died of before steroids were used to manage the disease. Adkins' die of kidney failure before they are eight months old. The normal lifespan of mice is two to three years.

With Roopenian as her mentor, Adkins is studying these doomed mutant mice to figure out the mechanisms behind the onset of disease. The mutation causes the mice to produce too much of a protein called interleukin 21, or IL21. Roopenian's team has known for a while that this protein has something to do with lupus. Normally, it helps the immune system respond to infections. But the scientists found that, when produced in excess as it is in their strain of mutant mice, IL21 leads to the symptoms of lupus.

"It turned out that it wasn't just lupus, but many other autoimmune disorders, too," says Roopenian. "We focus on lupus so we aren't going in 20 different directions at a time."

Now Adkins is studying the specific immunity cells (a subset of T helper cells) that produce the protein. Her goal is to figure out exactly how IL21 contributes to lupus, how it's produced and how it functions. Her work has already led to one significant finding.

Adkins found that these cells exist in healthy mice, even when they are not undergoing an active immune response. "That was a surprise. No one would have expected that," says Roopenian.

Next, the scientists want to figure out how those cells develop in normal mice, information that could illuminate what exactly goes wrong when lupus occurs. That would not only open the door to new therapies; it could have diagnostic value, too.

"Historically, has been extremely hard to diagnose. A lot of our effort is to understand the mechanisms much better so it will be easier to predict when people are showing early signs of it," says Roopenian.

It was serendipity that put Adkins, who has been interested in science and medicine since high school, on the Jax track in 2011. After studying genetics as an undergraduate at Central Connecticut State University, she knew she wanted pursue a Ph.D., but she wasn't sure if she wanted to focus on genetics or immunity. The mammalian genetics program allowed her to marry her two interests. The Jax track, she says, also gives her access to the breadth of research at Tufts and the depth of genetic expertise at the Jackson Lab.

"It's nice to have the two names together," she says of the new program. "It adds more weight to what I'm doing."

"Liz has an innate drive to think scientifically and to come up with answers," Roopenian says of Adkins. "As the first [Jax track] student, she is really setting a high bar for everyone else."

Explore further: Genetic mutation causes lupus in mice

Related Stories

Genetic mutation causes lupus in mice

January 3, 2014
Yale researchers have identified a genetic mutation that leads to lupus in mice. The discovery could open the way for development of therapies that target the mutation. The study appears in Cell Reports.

Putting Lupus in permanent remission

November 11, 2013
Northwestern Medicine scientists have successfully tested a nontoxic therapy that suppresses Lupus in blood samples of people with the autoimmune disease.

A nanogel-based treatment for lupus

March 1, 2013
Systemic lupus erythematosus (SLE) is disease in which the immune system mistakenly attacks healthy tissues, resulting in inflammation and tissue damage. Current treatments are focused on suppression of the immune system, ...

Researchers identify gene variants that may cause kidney problems in lupus patients

August 22, 2013
Variants in a particular gene are linked with an increased risk for kidney complications in patients with lupus, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). ...

Chronic exposure to staph bacteria may be risk factor for lupus, study finds

August 8, 2012
Chronic exposure to even small amounts of staph bacteria could be a risk factor for the chronic inflammatory disease lupus, Mayo Clinic research shows. Staph, short for Staphylococcus aureus, is a germ commonly found on the ...

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.