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Summer Intern Alexandra Levitt is Lead Author on ATC Pulmonary Study

By Eddy Ball
February 2007

Alexandria Levitt
Levitt clowns in front of the LRB staff photo board. (Photo courtesy of Dianne Walters)

Diane Walters
Levitt's Summers of Discovery mentor Dianne Walters (Photo courtesy of Steve McCaw)

Last August, high school senior Alexandra Levitt returned to classes with more than memories of a good time during her summer in RTP and a technological edge in senior biology classes. When she went back to school in Philadelphia after working on a study of airway responsiveness at NIEHS, she could look forward to presenting the results of her summer's work in May at a poster session at the 2007 American Thoracic Society's 2007 International Conference in San Francisco.

Under the direction of Laboratory of Respiratory Biology (LRB) Chief Steve Kleeberger, Ph.D., and post-doctoral fellow Dianne Walters, Ph.D., who served as her mentor, Levitt explored a research interest she had developed during the previous summer, when she worked in drug development for a pharmaceutical company. Levitt, who plans to study medicine, examined the effects of the neurotransmitter serotonin on airway responsiveness in strains of inbred and chromosome-substitution strains of mice.

She worked with Kleeberger and Walters on the study, and several additional LRB colleagues contributed to the study, including Biologist Wesley Gladwell, Contract Biologist Jessica Martin and Technician Katharine Holder. The study showed such good potential that Walters, Gladwell and Martin will continue work on the study and hope to publish a journal article further exploring the genetic aspects of lung response to serotonin, which will credit Levitt as one of the contributing authors.

Levitt was one of 18 high school participants in the NIEHS Summers of Discovery Research Program. She is a student at the Springside School in Philadelphia, which she has attended since ninth grade, and lives with her family in the nearby township of Horsham. Her father, who is a physician, knew of Kleeberger's laboratory at NIEHS and suggested she apply to the program and stay with relatives in the area.

"Summers of Discovery was a great program," Levitt said. "It was amazing to work with a Ph.D. scientist who knew so much and spent so much time with me." Being at NIEHS, with its state-of-the-art equipment and facilities, "showed me how big environmental medicine is and how it interacts with so many other medical fields." Working with Walters was an important part of her NIEHS experience. Walters was a mentor for the young investigator, helping her learn laboratory basics and design the study, and a good role model.

Levitt said that she has always been drawn to medicine and its potential for helping people. She credits her family with encouraging her to pursue her interest in science. She also appreciates the way her small, all-girls school nurtured her and her classmates in the ninth and tenth grades before putting them together with boys in junior and senior science classes. "It was the best of both worlds," she observed. "I had a chance to build up my self-confidence, and by the time I had to be in a class with boys, I was ready for it."

Authoring a study presented at an international conference is obviously an important accomplishment for an aspiring scientist, and no doubt the study will impress college admissions officials. However, Levitt is more than a scientist; she has a broad range of interests and achievements that should impress any college she chooses. She writes and draws, enjoys volleyball and horseback riding, has volunteered at a riding program for disabled children and is the editor of her school's literary magazine.

The summer's work was also rewarding for Walters, who was impressed by the intern's attitude toward the challenges of working in the lab. "This was a good mentoring opportunity for me," Walters said. "It's unusual to find a high school student who not only has a high level of knowledge, but also an interest in the work and a dedication to doing the best job she can."

Levitt recently attended a five-day writing retreat in Montana and stays very busy with extracurricular opportunities through her school and community. As she looked ahead to what she'll do this summer, she talked of more personal time than she's had for years. "I want something less structured this summer," she said.

Levitt A, Gladwell W, Walters DM, Martin JR, Holder K, Kleeberger SR. Inter-strain variation in airway responsiveness to serotonin. NIH/NIEHS, RTP, NC

Introduction: Airway hyperresponsiveness (AHR) is a hallmark of asthma and other chronic respiratory conditions. Studies examining AHR to cholinergic agonists have identified quantitative trait loci (QTLs) on several chromosomes; however, few studies have investigated the genetic basis of AHR to serotonin (5-HT), a potent bronchoconstrictor released from mast cells. The current study was designed to identify the genetic basis of differential susceptibility to 5-HT-induced AHR in inbred mice.

Methods: Fifteen inbred strains of male mice (JAX) were assessed for changes in pulmonary function in response to 5-HT using the flexiVent® system. Briefly, mice were anesthetized, cannulated, paralyzed and ventilated at 150 breaths/min with a tidal volume of 7.5 ml/kg. Airway resistance was measured every 30 sec for 5 min after a 10 sec aerosol of 5-HT (10 mg/ml) or phosphate buffered saline (PBS). Peak resistance values were reported as the mean + SEM for each strain (n=6-8/strain).

Results: A comparison of inbred strains revealed significant inter-strain variation in 5-HT-induced airway resistance. C3H/HeJ mice were the least responsive and BTBR T+ tf/J mice were the most responsive to 5-HT (1.0650 cmH2O.sec/ml vs 16. 9327 cmH2O.sec/ml, respectively). There were no significant differences in airway resistance at baseline or in response to aerosolized PBS between strains.

Conclusions: Differential responses in inbred strains of mice indicate that there is a significant genetic contribution to 5-HT-induced increases in resistance. Future studies will identify the mode of inheritance and candidate genes for this model.

Funded by NIEHS Intramural Program.

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