Inside Salk; Salk Insitute

Next Generation: Laura Tan

Laura Tan

When Laura Tan got a request to present a two-minute elevator pitch on her work to faculty and high-end donors, she got a little nervous. When she heard that actor/director Robert Redford and Salk Board Chair Irwin Jacobs were expected to be in the audience, she got excited.

“It was really, really fun,” says Tan, a research associate in the Laboratory of Neuronal Structure and Function led by Paul Sawchenko. “With two minutes, you really can’t get into detail. You are giving a teaser trailer like a movie, just giving little snippets so they come talk to you afterwards.”

As it turned out, Jacobs and Redford missed Tan’s talk–which included a PowerPoint slide of Fort Knox to represent how impenetrable the brain can be–but rather than crestfallen, Tan channeled her customary ebullience into the rest of the evening. Several attendees–people she would probably not have met otherwise– approached her to learn more about her work on how the brain perceives and processes stress signals. And she did get to chat with Jacobs and Redford at the evening reception, where Redford requested meeting the postdoctoral researchers.

“It’s kind of nice to be a rock star in research for two minutes,” says Tan. Game to try anything– be it stopping a fast break in lacrosse or lending her alto to a choir–Tan is fueled in part by the three cups of coffee she drinks every day and in part by an insatiable curiosity for what makes the brain tick, particularly when it’s under siege by stress. For the past year, she has turned her considerable energy to studying stress and its effect on Alzheimer’s disease.

One of the problems with treating Alzheimer’s is that drugs have difficulty crossing the bloodbrain barrier, a highly selective fortress that keeps pathogens out of the brain by separating circulating blood from the brain’s extracellular fluid in the central nervous system. That makes delivering a beneficial central nervous system drug in a pill or blood injection difficult, as it has to flow through the entire body with perhaps little, or none, of the drug getting into the brain. It can create toxicity problems along the way, affecting the liver, heart, digestive tract and more. And the stress receptor Tan is targeting exists outside of the brain as well, creating more complications for treatment.

If the brain is like Fort Knox, says Tan, the rest of the body is like the Kentucky countryside.

“We could go in with planes and tanks to try and get to the gold in Fort Knox, but it would destroy most of Kentucky in collateral damage, which is extraordinarily bad because I like bourbon,” she jokes. “In this metaphor, drugs designed for the brain can destroy the body and never even reach their target.”

Tan is investigating alternative ways of delivering drugs that block corticotropin-releasing factor (CRF) receptors that are both efficacious and targeted to the brain and that do not require invasive procedures (such as brain surgery) for the treatment and prevention of Alzheimer’s disease.

“We are using a sneaky Ocean’s 11 approach where we are coming in through the back door,” Tan says. “We are going with a smaller team. We are getting in and out with the gold without destroying anything outside.”

Image courtesy of Anna Scipione

To accomplish this, Tan uses an intranasal administrator, similar to an asthma inhaler, to deliver drugs precisely to the upper olfactory region of the nasal cavity in her mouse models. Neurons in the mucous membrane that lines the nasal cavity send their axons through the skull to the brain, the same pathway that gives humans their sense of smell. Using this noninvasive route, Tan and her colleagues have been able to show that it can transport lower doses of drugs–in this case, a compound that binds to one receptor–across the blood-brain barrier, thereby sparing peripheral tissues from exposure.

“CRF was discovered at Salk in Wylie Vale’s lab in 1981,” Tan says. “The fact we are pursuing this feels organic. It’s a very Salkian thing to do.”

Tan, 33, hails from Mississauga, the sixth largest city in Canada. Her father, a chemical engineer, and her mother, a social worker, never pushed her toward a science career, but she was inspired by her uncle, Larry Tan, who discovered the first acellular vaccine for pertussis. The vaccine contains cellular material but not whole-cell bacterium to invoke an immune response to create antibodies in the patient.

Tan always thought she would be a medical doctor until her senior year at the University of Toronto when she got her first taste of lab life and was hooked. Up to that point, she felt her studies had been all about memorizing and regurgitating information.

“We do that here, too, but I feel we are creating the knowledge,” Tan says. “I don’t have to be the encyclopedia, but I do have to use the encyclopedia and then apply it to what I’m doing. I like science because I get to ask the questions I want to ask.”

Characteristically, Tan plunged head first into the sprawling 50,000-student experience of the University of Toronto. In addition to biology and humanities coursework, she organized an intramural sports program, playing on more than 100 teams. The “Laura A. Tan Award” was created to honor her contribution to athletics at the college.

Graduating with distinction in zoology/biology with a minor in classical civilizations, Tan remained at the University of Toronto to earn her PhD in neuroscience. She did her doctoral studies under David Lovejoy, a former Salk postdoctoral researcher in Vale’s lab.

When she began casting her net for a postdoctoral position, Tan was initially attracted to Europe. Then fate intervened in the form of an advisor who told her, “If you want culture, go to Europe. If you want science, you go to the United States.”

Taking that advice to heart, Tan reached out to Salk, and Sawchenko specifically because of his reputation as a good mentor and his mastery of anatomy.

“It was such a good fit,” she says. “I remember emailing Paul and getting a response back in three hours. That was one of the greatest feelings.”

Tan joined Salk in 2011 and slipped into Institute life like a hand into a glove–organizing networking opportunities for researchers and volunteering for a plethora of other Institute events. Almost immediately upon arriving at Salk, she answered an internal bulletin board ad to join a softball team formed by Inder Verma’s lab. She encouraged her three colleagues to follow suit.

“We knew nobody in that lab. We just showed up and suddenly, we are all the best of friends,” she says. “So much so that everyone thinks I’m in the Verma lab.”

To relieve the stress she gets from studying stress, Tan also doodles. Many of her cartoons have a central theme of her in the lab being menaced by chocolate chip cookies and muffins, which bear a striking resemblance to a stain she employs when counting cells–the background is beige and the cells are dark brown. “I was terrified of chocolate chip cookies for awhile,” she says.

Sawchenko describes Tan as a “true Renaissance woman,” a highly creative and productive scientist who is also an accomplished athlete, chef and chorister with a schedule that exhausts him just thinking about it.

“From day one, she has been the unquestioned leader of my laboratory group, heading up not only collegial interactions within our group and between our lab and others at the Institute, but also spearheading such activities as our participation in science outreach to local high school students and holiday food collection drives,” Sawchenko says. “She is the kind of individual who enlivens a workplace, embodying a most rare combination of scholarly acumen, a strong work ethic and social conscience.”

At the Institute, Tan has learned that she likes, and is good at, mentoring the newer researchers. She embraced recruiting volunteers for Explore Salk earlier this year, taking her cue from another research associate, Amy Rommel.

“I always think of her as my prototype,” she says. “It’s like, ‘If I can be a little bit more like Amy, I’m doing okay.’”

Beyond the bench, Tan’s life is equally full tilt. She plays defense for the San Diego Lacrosse Club at nearby Doyle Park during the summer and at tournaments in Los Angeles, Las Vegas, Arizona and Hawaii, among other places. She discovered the club on Facebook and has been playing with the all-woman team since the day after she arrived in town. Tan also sings as an auxiliary member with Sacra/Profana, an eclectic local choir that frequently accompanies the San Diego Symphony, including for its Summer Pops concert paying tribute to Broadway shows such as Wicked, Rock of Ages and Les Miserables. And in her spare time, she bakes. Chocolate milk stout cupcakes with peanut butter buttercream are her signature sweet.

Four years into her time at Salk, Tan still marvels at her good fortune. “There is something about being surrounded by good people and the building itself,” she says. “Sometimes, I come in to work and give the Salk walls a pat as if to say, ‘Hey, hi friend. Nice to see you.’”