May 17, 2018
Her discovery expanded our knowledge of cancer genetics
BY Michael Hardy
Shortly after arriving at MD Anderson in 1987 as a junior faculty member, Guillermina Lozano, Ph.D., attended several seminars hosted by the center’s biochemistry department.
The biochemists giving the presentations were studying the role of transcription factors – proteins that regulate how genes express themselves. Lozano, a geneticist working to understand p53, a gene known to suppress tumor development, suddenly wondered if p53 could itself be a transcription factor.
“I went back to my office and pulled out the sequence of p53 and said, ‘oh, here’s this negatively charged domain that could attract the transcriptional machinery and here’s this positive domain that could bind DNA. Maybe it is a transcription factor.’ So then we planned the experiments that would test that hypothesis.”
The experiments proved the hypothesis correct and Lozano published her findings in the journal Science, establishing her reputation as one of the world’s foremost cancer researchers. In 2017, she became the sixth MD Anderson scientist elected to the National Academy of Sciences, but the first chosen for research conducted while on faculty at the institution.
The road to a career in research
The daughter of Mexican immigrants, Lozano was born and raised in East Chicago, Indiana, where her love of science was kindled by her teachers at Bishop Noll, a private Catholic high school. In her senior year, however, her family moved to McAllen, Texas, to be closer to their Mexican relatives, and Lozano was forced to adjust to a less challenging public school.
After graduating, she enrolled at nearby Pan American University (now the University of Texas-Rio Grande Valley).
“I grew up in a Mexican-American culture,” she recalls. “I’m a woman. I was expected to get married and have a family, I wasn’t expected to go to college. My father only let me go to Pan American so that if my future husband ever left me, I would be able to support myself.”
After graduating from Pan American, however, Lozano was accepted into a summer program at the National Institutes of Health in Bethesda, Maryland. She had planned to become a science teacher, but her experience at the NIH set her on a new trajectory.
“It was absolutely cutting-edge research,” she says. “I loved it. I was learning so much, and I had a great mentor who I still keep in touch with. That’s when I really decided research is what I wanted to do.”
Lozano’s NIH experience led to a job offer even further afield – Munich, Germany, where she was hired as a laboratory technician at the prestigious Max Planck Institute. Although she loved working as a tech, and enjoyed the opportunity to travel around Europe, Lozano knew she wanted to become a researcher in her own right, so she returned to the U.S. and got her doctorate at Rutgers University and the University of Medicine and Dentistry of New Jersey. She then completed a postdoctoral fellowship at Princeton University under renowned cancer researcher Arnold Levine.
It was at Princeton that Lozano first began cloning and manipulating mouse DNA to study how cancers develop. Not long after moving to Houston to join MD Anderson, her mentor Levine published a paper announcing the discovery of p53 as a tumor suppressor that regulates cell division to prevent tumors from growing. Because of its cancer-fighting abilities, p53 is sometimes called the “guardian of the genome.”
The power of p53
Lozano built on Levine’s breakthrough by establishing that p53 is a transcription factor. Her team then went on to recognize the physiological importance of two proteins, Mdm2 and Mdm4, that play a role in blocking p53 – and thus allowing tumors to grow. By manipulating these proteins, Lozano believes, clinicians may some day be able to stop cancers on the molecular level before they spread. Drug companies have developed experimental treatments based on her research, but so far they’re too toxic for use in humans.
“I think every tumor cell has to somehow dampen p53,” she explains. “For about 90% of tumor cells, we know what the pathway is – it’s either delete p53, or neutralize it by making lots of the inhibitors Mdm2 or Mdm4. We need to discover how the other 10% undermine the p53 pathway.”
Over the years, Lozano has fielded several offers from rival cancer centers. What keeps her at MD Anderson, she says, is the synergy and collaboration of the center’s basic scientists and its clinicians. It’s the same kind of intellectual cross-fertilization that led to her insight into p53 as a transcription factor back in 1987.
“I’m not a physician, but I understand that some of the problems they encounter are problems that I can study as a basic scientist,” she says. “We wouldn’t be the number one cancer hospital without the underlying the research that drives patient care. That collaboration is what keeps me here.”
Read more about Lozano's life and career in Conquest magazine.