Taylor Hancock describes herself as "a professional talker." As if to prove the point, the full-time college student and part-time radio disc jockey strides to the makeshift podium, with scenic Boston Harbor as her backdrop, and takes the microphone with the poise and energy of a seasoned presidential candidate.
"This is my first time in Boston, and it's really exciting!" The crowd of 300 or so, including many young and middle-aged women, responds with a cheer. "I have lupus. I actually wasn't diagnosed until last year, but I'm sure many of you are in the same boat, where you were sick for years and years and it took forever to get diagnosed."
Taylor is speaking at the Walk to Cure Lupus, an annual fundraiser for the Alliance for Lupus Research (ALR). The word "lupus" is an everyday stand-in for systemic lupus erythematosus, an autoimmune disease with symptoms ranging from a mild skin rash to organ failure.
On this sunny, breezy June day, Taylor's Walk "team" is a family affair. Derry Roopenian, Ph.D., a Jackson Laboratory professor who studies lupus, and who earlier addressed the walkers about the importance of funding research, is here with his wife, Shari, and son, Michael. Also making the trip from Bar Harbor is Taylor's first cousin, Mario Crisalli, a college student who is spending the summer working in Dr. Roopenian's lab.
"I'm sure many of you are aware," Taylor continues, with another sure-fire applause line for this crowd, "that there hasn't been a new FDA-approved lupus drug in 50 years, which is just not acceptable. So with the money you guys raise through the ALR, and Dr. Roopenian's research, we'll get things rolling. Thank you for being out here and have fun!"
Like many "professional talkers," when away from the microphone Taylor is rather reserved, the person in the room who listens to the conversation for a while and then comes up with the quiet zinger that makes everyone laugh. An accomplished gymnast through her high school years, she started noticing unaccustomed bone and joint pain, fatigue and other symptoms soon after enrolling at Oklahoma State University.
Taylor is among an estimated 1.4 million Americans—nine out of 10 of them female—living with lupus. The disease most often appears during childbearing years and affects African-American and Hispanic women in disproportionately large numbers.
Autoimmune diseases develop when the immune system, which is supposed to identify and vanquish potentially dangerous infectious agents, instead attacks the individual's own body. Most autoimmune diseases strike specific organs, such as the pancreas in type 1 diabetes. Lupus, however, is a systemic disease in which abnormal antibodies are produced throughout the body, inflaming a variety of tissues and organs, including the skin, heart, lungs, kidneys and brain.
Diagnosis of lupus is tricky because most symptoms—such as skin rash, low-grade fever and painful joints—are common to other diseases. And to further complicate matters, symptoms usually come in alternating periods of flares and remissions.
Back at The Jackson Laboratory, Mario shows his cousin around the Roopenian lab, introducing his mentors Caroline McPhee, D.V.M., and Jason Bubier, Ph.D. At 6 foot 4 inches and a muscular 260 pounds, Mario somehow looks even bigger in a white lab coat. About to enter his senior year at Salisbury University in Md., Mario had begun the summer with plans to attend medical school but is now thinking about a career in basic research. He says Taylor's condition has been a powerful motivator in his summer work.
"When someone in your family has a medical problem, you just want to find something that can help," he says. "When I go into the lab, I think about her."
After some obligatory cousinly teasing, Taylor and Mario sit down with Derry so Taylor can learn how his laboratory is tracking down the causes of lupus, with the goal of finding new ways to treat or even prevent the disease. According to Derry, understanding the disease involves two kinds of white-blood cells, T cells and B cells, that are key players in the extremely complex immune system.
"We know that B cells, which produce antibodies, are way too active in lupus patients," Derry says. "But B cells can't become active unless a T cell tells them to," he explains. "And, there's a particular protein made by T cells that is overproduced in lupus patients." That protein is interleukin 21, or IL21.
Derry and his laboratory, together with collaborators at the National Institutes of Health, reported that a mouse model of lupus, bred with a deficiency in the receptor for IL21, stayed healthy and exhibited none of the symptoms of the disease. Since it's not possible to knock out the relevant IL21 gene in humans, Derry says, "the next step for us is to figure out how to therapeutically target IL21 and inactivate it." This year he—one of the ALR's first grantees in 2001—received a new grant from the ALR to conduct that research.
Derry's lab is also pursuing other avenues in lupus research, including Mario's project, which is to test a potential drug target (a molecule called Qa-1) to see if it can reduce the mortality of mice with an especially severe form of lupus.
Taylor thanks Derry and Mario for their work, and says she and her parents have been active in urging Congress to provide more research funding for lupus. "When my dad and I were in Washington at the beginning of March for Lupus Advocacy Day, the Lupus Foundation of America was also pressing for a national lupus patient registry."
By early August, as Mario and his fellow Jackson Laboratory summer students were completing their research reports, clinical trials of a drug called Benlysta were making headlines, showing promising results in reducing the severity of lupus symptoms. Benlysta inhibits the activity of B-lymphocyte stimulator, or BLyS, a protein that directs the formation of B cells.
Derry hails the news. "This is a very complicated disease, and it's going to take lots of work to find and isolate all the mechanisms involved in lupus and figure out how to thwart them.
"We want to stop lupus in its tracks," Derry says with a determined smile.
Taylor puts it differently: "Lupus sucks." She notes that three drug categories are approved by the FDA to treat lupus, "but they just treat symptoms, and some of them have terrible side effects, like organ failure, infertility and cancer. We need to raise awareness and support so Dr. Roopenian and other researchers can find a real cure."