Magical and molecular motif weaves its way through Jennifer Cochran’s career
BY JESSE BOYETT ANDERSON
Jennifer Cochran, assistant professor of bioengineering, and fourth-year graduate student Jennifer Lahti.
Jennifer Cochran was hardly a born chemist. As a teenager with a strong passion for music, she didn't dream of finding treatments for cancer and helping persistent wounds heal. After high school, she enrolled at the University of Delaware as a communications major. One semester later, she realized this field was not for her. To find direction, she went to the local community college and, with some apprehension, signed up for first-quarter chemistry.
In the laboratory, something clicked. "It was magical in a sense," Cochran said. "I had an overwhelming desire to know why the chemical reactions were happening so as to change the color of a solution or to form a desired chemical product."
Cochran joined Stanford as an assistant professor of bioengineering in 2005, nearly two decades after walking into that first chemistry lab. Now she studies the chemical reactions that allow cells in the body to talk to each other; then she attempts to manipulate these communication pathways in ways that benefit human health.
"We have molecules in our body that carry out all of these processes that we do not even think about," she said. "How do they function? How has nature evolved them to function, and how can we use this information to help them function better?"
This push to apply basic science knowledge to real-world problems is called "translational research." For applying her understanding of biochemistry to help molecules function better, Cochran was named the 47th Mallinckrodt Faculty Scholar, a three-year endowed award for innovative medical research.
"Excellent work," said Russ Altman, chair of the Bioengineering Department. "Since coming to Stanford, Jennifer has engineered improved versions of a number of important proteins with potential applications in healthcare, and she has outlined a research vision that will push the frontiers of protein bioengineering to new capabilities."
Her research vision includes two main directions: regenerative medicine (or helping the body heal itself) and cancer.
Doctors worry when a diabetic patient injures a foot. Complications of diabetes impede wound healing on the extremities and can even lead to amputation. Cochran's manipulation of one molecule—epidermal growth factor (EGF)—involved in the healing process may help shorten recovery times for diabetics and others with chronic or extensive injuries.
EGF aids wound healing by attracting new cells to the site of an injury and then encouraging them to divide, producing more cells to replace the injured ones. A fourth-year graduate student in Cochran's lab, Jennifer Lahti, is studying the darker side of this process.
Some cells, including breast cancer cells, put up extra antennae, or receptors, to detect EGF. This makes them extra-sensitive to even small quantities of the molecule. When the receptors detect EGF, they tell the cell to divide. As the cells divide, the cancer grows.
Lahti is engineering molecules that prevent the receptors from detecting EGF. By blocking this signal, Lahti hopes to slow or stop tumor growth.
Before cancer can be treated, it must be identified. Cochran and Sanjiv Sam Gambhir, professor of radiology and a pioneer in the field of cancer imaging, are developing noninvasive ways to diagnose cancer and track changes during the course of treatment. Such technology could save lives and money by allowing doctors to change course immediately if a given treatment regimen isn't working.
Cochran's contribution to this collaboration involves the creation of markers for receptors, such as "integrins," that are present in high numbers on tumor cells. Integrins help tumors—including those from breast, brain and prostate tissue—grow their own blood supply. In healthy tissue, certain integrins help cells stick where they belong, migrate to a new location or communicate with other cells.
Cancer cells send too many or the wrong kind of integrins to their surface, effectively harnessing the molecule's stickiness and triggering the growth of new blood vessels. The newly formed vasculature feeds the tumor and provides a route for small pieces of the tumor to travel to other parts of the body, a process called metastasis.
In addition to tracking tumors by looking at the distribution of integrins within the body, Cochran hopes to develop tools to help destroy tumors by blocking the action of integrins and other receptors in forming new blood vessels, thereby cutting off the tumors' food supply and escape route.
Much of Cochran's work relies on two complementary techniques, molecular design and directed evolution, the latter of which she learned as a postdoctoral fellow at the Massachusetts Institute of Technology.
While in Dane Wittrup's lab at MIT, Cochran directed the evolution of novel EGF molecules that stayed in closer contact with their receptors for longer periods of time than naturally produced EGF. To do so, she intentionally altered the DNA that codes for EGF in yeast cells. She then sorted through the hundreds of millions of resulting mutants to find those yeast cells that produced "stickier" EGF. Cochran and her colleagues are now testing these molecules for clinical application in wound healing.
Wittrup recruited Cochran to his lab at an MIT Biotechnology Training Grant retreat. Her clever technical and analytical approach to understanding how one part of the immune system can be activated to fight disease impressed him. She continued to impress during her time in his lab.
"In any group there is someone that everyone goes to ask advice and run ideas by. People go and hope that some of the magic rubs off on them," he said. "Jennifer was that person."
While others may go to Cochran for advice, she credits her husband, Frank, for some of her success.
"He was incredibly supportive of my decision to pursue an academic career, and took time out from his own research projects to help set my lab up," she said.
Although both received bachelor's degrees in chemistry from the University of Delaware, they did not meet until graduate school at MIT. Their mutual passion for chemistry propelled them into a game of professional leapfrog. While Cochran learned directed evolution from Wittrup, her husband finished up his doctoral work and began a fellowship at the University of Pennsylvania. Cochran joined him there as a fellow for nine months before they both came to Stanford. Frank is now a postdoctoral fellow in Stanford's Molecular Imaging Program. To all appearances, the leapfrogging worked.
"We were thrilled to recruit her," said Philip Pizzo, dean of the School of Medicine, which co-sponsors the Bioengineering Department along with the School of Engineering. "She has certainly met and exceeded our expectations as a highly promising and creative faculty member."
Cochran's advisees appreciate the young faculty member's personal attention and excitement. She holds weekly one-on-one meetings with each student and runs her lab on the artisan model: Lab members follow projects through from conception to publication.
"I really like that personal touch, especially as a graduate student trying to get research going," said Stephen Lee, in his second year, studying the behavior of novel EGF molecules in wound healing.
"Our lab is so small that Jennifer is intimately involved in a lot," Lahti said. "She seems to have a passion for seeing each of our projects through to the end."
Cochran hopes to spread her excitement and sense of magic beyond the walls of the ivory tower.
"It is important to introduce students, in particular women and disadvantaged youth, to the sciences and engineering at a young age," Cochran said.
Last summer she collaborated with a local high school teacher to develop bioengineering lab modules for use in high school classrooms. She also set the wheels turning to host first-generation, college-bound high school sophomores and juniors from underrepresented groups in her lab for several years of summer research.
Cochran is no stranger to science outreach. According to her dissertation adviser, Larry Stern, currently a professor of pathology at the University of Massachusetts Medical School, she starred in a chemistry outreach program, known as the magic show, for high school and elementary school students while in graduate school at MIT.
"She would do the sparks flying, smoke blowing and all of that other stuff," Stern said.
Although she no longer sends off actual sparks and smoke, Cochran has retained the sense of magic that led her first to chemistry and then to bioengineering.
Jesse Boyett Anderson is a freelance science writer.
