New Whitehead Fellow Kate Rubins studies infectious disease

CAMBRIDGE, Mass. — When she was in high school in the early 1990s, Kate Rubins’ parents enrolled her in a student-led HIV education outreach program. Part of her parents’ goal, Rubins suspects, was to scare their daughter away from any and all dangerous behavior.

“But mostly, I became fascinated with the science,” says Rubins. “This was in the early days of antivirals, and the promise of science was just starting to emerge.”

Nearly fifteen years later, Rubins is relentlessly pursuing the area of inquiry that her high school program inspired. Last month, after completing her doctorate at Stanford University, Rubins joined the Whitehead Fellows program.

A Whitehead Fellow is a recent PhD graduate who has demonstrated such exceptional promise and is given the space, resources and support to start and run his or her own labs, minus the traditional faculty responsibilities. After about five years, Fellows are primed for top faculty posts. (For a list of former Fellows and their current positions, visit http://wi.mit.edu/people/fellows/former.)

“I'm impressed with how skillfully Kate is exploring the molecular workings of a bevy of viruses,” says Whitehead Director David Page, himself a former Fellow. “It's clear to me that she is on her way to becoming a leader in this field.”

Probing pox

Rubins began her undergraduate research focusing on HIV and coauthored her first paper while still a junior in college. By the time she entered graduate school at Stanford, she had changed her focus to poxviruses, a class that includes not only smallpox but cowpox, monkeypox and vaccinia—the virus from which the smallpox vaccine is developed.

During this period, Rubins was part of the research team that developed the first animal model of human smallpox.

“Smallpox has been around for thousands of years, but the virus only infects humans,” says Rubins. “That’s good for us because it allowed the World Health Organization to eradicate it. We’ve had it in the freezer since the 1950s, but no one had successfully created an animal model.”

Rubins and her colleagues succeeded in creating such a model in the primate Cynomolgus macaques, publishing their results in 2004 in the journal Proceedings of the National Academy of Sciences.

Rubins’s primary contribution to the program was developing a microarray platform in which she could study how the mammalian immune system responds to this pathogen. She found that in the presence of smallpox, immune cells release an alarmingly high number of cytokines—proteins that act as intracellular regulators during an immune response.

“We call it a cytokine storm,” says Rubins. “It almost looked like the blood condition sepsis, where a major release of cytokines can cause organ failure”

However, one particular cytokine, called TNF alpha, was missing from the blood samples. This was surprising, because TNF alpha is one of the most common immune system proteins. “We have reason to believe that smallpox codes for a TNF alpha decoy receptor that inhibits TNF alpha signaling and that dupes the immune system,” she says.

The eradication of smallpox by no means detracts from the value of this work. Potential bioterrorism threats aside, immunologists need to know how these pathogens work. And learning their tactics teaches us a great deal about human immunity as well.

“If you knew nothing about the immune system, and you just looked at how smallpox interacts with it, you’d immediately learn about interferons, cytokines and the protein complex NF-kappaB, to name a few,” Rubins points out. “You’d have all the innate immune responses laid out for you. What makes smallpox so fascinating—and so scary—is that it acts in ways that no other viruses does.”

Working at Whitehead (and away)

Rubins was attracted to Whitehead mainly by the balance of basic science and clinically oriented biomedical research. “The caliber of the faculty here goes without saying,” she emphasizes. “And the Fellows program is unique.”

At Whitehead, Rubins will study tissue culture models of vaccinia. She will also continue a project she has begun with the U.S. Army to develop therapies for Ebola virus, as well as conducting field studies in the Democratic Republic of Congo to research monkeypox.

All live viruses will remain at the Centers for Disease Control in Atlanta, Georgia and the US Army Medical Research Institute of Infectious Diseases, in Frederick, Maryland. No infectious samples will be brought back to the Institute.

“No smallpox samples are ever allowed to leave the Atlanta facility,” she says. “They remain in securely-guarded, Biosafety Level 4 conditions.”

Rubins joins current Fellows Thijn Brummelkamp, Fernando Camargo, Hui Ge, Andreas Hochwagen and Paul Wiggins.