Kulesa Lab

Paul Kulesa, Ph.D.

Director of Imaging/Kulesa Lab

Professor, Department of Anatomy & Cell Biology
  The University of Kansas Medical Center

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Over the course of his career, Paul Kulesa, Ph.D., Director of Imaging at Stowers, has set his sights on some very different universes. Raised in Chicago, Kulesa attended Notre Dame where he received a BS in Aerospace Engineering in 1984 and immediately went to work as a NASA engineer.

Multispectral image rendered from a 3D confocal z-stack through the early chick embryo, showing the position and cell-cell interactions of migrating neural crest cells that pattern the face and neck.

Image: Courtesy of Dr. Paul Kulesa

As part of the propulsion and payload operations teams at Houston’s Johnson Space Center, Kulesa’s job was to determine propulsion requirements for payloads as part of the Space Shuttle and Hubble Space Telescope programs. At NASA he rubbed elbows with giants of the American space program like astronaut John Young (who had driven the Lunar Rover) and legendary flight director Gene Kranz.

“There was a lot of talk about planning a manned mission to Mars back then, using surface data from more sophisticated probes than Viking and developing long duration space flight,” says Kulesa, who for a time considered becoming a payload specialist/astronaut. “I knew an engineer could design complex orbital rendezvous missions and become a payload specialist, but most of these folks had Ph.D.'s. I realized that I needed to go to grad school.”

Kulesa began graduate work in applied mathematics and obtained an MS at the University of Southern California followed by a Ph.D. in 1995 at the University of Washington. His Ph.D. mentor was James D. Murray, an expert in the mathematics of biological pattern formation. With input from his advisor and a mix of biologists and mathematicians on his thesis committee, Kulesa applied mathematical modeling to predict the spatial patterning of teeth primordia in alligators, work published between 1996 and 1998.

He briefly considered postdoc’ing at the NASA/Ames Research Center but was discouraged by the slow pace of doing experiments in space. Luckily, about that time Scott Fraser gave a seminar at the University of Washington. Fraser, who directs a large interdisciplinary lab at Caltech, is a pioneer in developing imaging tools that allow the visualization and study of complex cell dynamics in living embryos.  

Intrigued, Kulesa approached Fraser about postdoc’ing in his lab to “combine theory and experiment.” With support from the Sloan Foundation, and later as a Burroughs Wellcome postdoctoral scholar, Kulesa moved to Caltech to launch his experimental career. “At the time the Sloan Foundation was supporting programs to expose physical scientists to experimental biology,” say Kulesa.

In the Fraser lab, Kulesa addressed the movements of the neural crest, cells that stream from the neural tube and form the peripheral nervous system, cranio-facial features, and melanocytes, among other structures. Using the chick embryo as a model system, he undertook time-lapse analysis of neural crest migration by cutting a hole in the eggshell and inserting an oxygen permeable, liquid impermeable Teflon window to enable microscopic observation of cell migration inside a living embryo. That study, published in Development in 2000, showed that neural crest cell trajectories, rather than being preprogrammed, are sculpted by cues from the microenvironment and cells they interact with along the way.

A 2002 Science paper followed showing that cells found in segmented cuboidal structures called somites, which give rise to bones and muscle, moved across the presumptive somite border and violated gene expression boundaries thought to correlate with the somite border. The study was a technical tour-de-force and provided a spatiotemporal framework for linking gene expression with cell movements. 

Rotation of a 3D confocal z-stack highlighting fluorescently-labeled (pMES-Green and PCS-mem-mRFP1-Red) migratory neural crest cells in the living chick embryo.  The movie reveals the beautiful, long cellular extensions of an individual cell.

Image: Courtesy of Dr. Paul Kulesa

Kulesa was recruited to Stowers in 2003 to provide a vision for the future of imaging at the institute and the imaging center, whose mission is to enable high quality light microscopy and the development of state-of-the-art methods for 3D live cell and embryo imaging studies. He also directs his own research program into cell migration in development and cancer.

Emulating the Caltech model, Kulesa’s team has biologists sitting beside imaging technology experts who develop tools such as photoactivation cell labeling and laser capture microdissection techniques. Another method, called “No Cell Left Behind” by Kulesa employs multispectral detection to identify and trace cell trajectories in dense tissue by their spectral id in addition to shape and brightness. 

“Spectral imaging has its roots in planetary studies,” says Kulesa, who used the technique to detect positions of individual multicolor-labeled migratory crest cells in an embryo in a 2010 BMC Developmental Biology study. “NASA uses spectral detection methods to identify Earth and planetary atmospheric and surface signatures, so why not label and detect cells with different colors in the same way?”

His group is also investigating neural crest-related cancers such as melanoma. In a 2006 PNAS study they showed that human metastatic melanoma cells transplanted into the embryonic chick neural tube migrate to neural crest target sites, where some revert to neural crest-like cells. These studies suggest that signals within the neural crest microenvironment may reprogram the metastatic phenotype of tumor cells.

Outside the lab Kulesa has a passion for surfing. “I have three surfboards in a garage in Pasadena and three skateboards in Kansas City, when I can’t make it to the ocean,” says Kulesa, who periodically asks his wife to tow him on his skateboard around the neighborhood in her VW bug. He makes a point of combining surfing with travel, with the goal of surfing all the breaks featured in the 60’s surf movie Endless Summer.

Kulesa still keeps track of the space program through friends. He is excited about the Mars Science Laboratory and other unmanned programs and would love to see NASA be more ambitious about a lunar colony and manned Mars mission. “I think we owe it to kids interested in mathematics and the life sciences to provide exciting frontiers for discovery, but right now I’m happy visualizing those frontiers within an embryo.”