José Maldonado was sitting in a large undergraduate biology class at UCLA when a guest lecturer delivered the astounding news: There is cell division in the central nervous system of adults. For more than 100 years, science had held that brains stopped developing after birth. You arrived with a complete set of brain cells, and that’s all you could count on to get you through life. To learn now about something scientists call adult neurogenesis "was really mind blowing," José says.

Fast forward a couple of years and José was telling a friend about his interest in adult neurogenesis when an eavesdropping teaching assistant told him her lab was working in that area and suggested he look them up. Another fast forward, and José, now a graduate student, had joined Michael Sofroniew’s research team, which studies the response to injury and degeneration in the nervous system. Through a bit of serendipity, Professor Sofroniew says, "We had bred some mice to study an injury model, and we noticed that adult neurogenesis was missing," and the result was "a unique model to study the role of adult neurogenesis." Stepping forward enthusiastically to pursue the new agenda was José, whom Professor Sofroniew describes as "inquisitive, persistent, and patient with things that are sometimes tedious," qualities that would serve him well.

Using the mice whose genes had been altered so they produce no neural progenitor cells, José compared them with normal mice. The altered mice seem "fine and normal and healthy" in most respects, José says, but when their brains are examined, two areas are "about half the size of control animals." The conclusion: Neurogenesis is replenishing brain cells throughout life, and the difference is "not just a small contribution." The two areas that receive new cells are the olfactory bulb, which controls the sense of smell, and a part of the hippocampus related to short-term memories. The research team wonders why "only those two regions receive cells throughout life," José says. "What are they doing on a cellular level that requires new cells?"

His dissertation research is the first to document that "a brain region requires the constant addition of new cells to maintain the complete complement it needs to function throughout life." He doesn’t feel ready to stop there, however. Instead, he’s planning a short postdoctoral stay at UCLA to look at other questions. Research elsewhere has already shown that adult neuroprogenitor cells travel about a centimeter in rodents, and much farther in larger animals and humans, from where they are formed to where they are needed. This happens via a cell "that forms a well-defined tube" and, probably, some chemical cues. José would like to know what happens at the destination. Thinking of the new cells as new kids at school, he wonders: "How does that kid know who to hang out with? What classrooms to show up in? And how does it change the environment it finds."

José’s research doesn’t involve humans. Nevertheless, diseases like Alzheimer’s and Parkinson’s have been associated with the disappearance of cells in certain parts of the brain. Understanding what happens during adult neurogenesis in mice "might suggest a way to help replace neurons that are lost in injury or disease," Professor Sofroniew says. It may take a long time to achieve that outcome, he says, but "If we don’t work on it now, it won’t happen."

Over the long-term, José is hoping to build an academic research career combining laboratory work with teaching. Besides serving as a teaching assistant in classes for undergraduates and for medical students, José has taken some time to return to his alma mater, the California Academy of Mathematics and Science, to talk with those who are following in his footsteps.

Located at Cal State Dominguez Hills, the California Academy introduces a select group of underrepresented minorities to science and math at an accelerated pace. Starting in 11th grade, students are required to take college classes—calculus, genetics, physics, and chemistry, in José’s case. As a result, his transition to UCLA was relatively smooth, and that’s a message he wants today’s academy students to hear. "It might not always be such a struggle," he tells them. "You should be prepared to work hard, but if your attitude is really positive and your goals are well-defined and you’re motivated, there’s no reason why you can’t succeed."

It also helps to have a timely push. José’s first push came from a sister who bought him a toy microscope when he was 8 years old, leading him to a closer examination of the leaves and rocks in his home environment. "I remember using the microscope until it broke," he says. A second and more crucial push came from David Krantz, professor of Psychiatry and Biobehavioral Science and his undergraduate research mentor. As he went through college, José knew he was "in full-fledged love with science," but he "had no idea how to turn that into a profession." Professor Krantz showed him "what it’s like to come in every day and do the work of science, the work it takes to get a big project done," José says, and encouraged him to consider graduate studies. For his part, Professor Krantz recalls that José "was one of the first people to join my lab when I got to UCLA, and he played a major role in helping me set up." José "is a pleasure to work with and has an infectious enthusiasm for science," Professor Krantz says. "I was thrilled when he decided to attend graduate school at UCLA."

José is somewhat unusual in doing both his undergraduate and graduate studies at UCLA and even rarer in his choice to stay here for a postdoctoral year, when many newly minted PhDs "are looking to get far away from the home lab," José acknowledges. His research is too compelling, however, to put down and walk away. "Here’s this giant puzzle," he says, "and I happen to be alive at a time in history when it hasn’t been solved yet. I have an opportunity in some small part to help solve it." In any case, he says, "I’ve been given so many opportunities here at UCLA that I haven’t had a chance to leave."

Published in Spring 2007, Graduate Quarterly