An “Energy Force” in Understanding Stem Cells

On Friday afternoons, the five young faculty members recently recruited to the UCLA Institute for Stem Cell Biology and Medicine can often be found sitting together, taking a break from their investigative work to cement personal bonds and reflect on their good fortunes.

“We call these our ‘Assistant Professor Sessions,’” quipped Hanna Mikkola, M.D., Ph.D., a former Harvard stem cell scientist who was first among the five faculty members hired by the new institute since it was established last year. “We sit around feeling sorry for our colleagues who went to other places—our lives and careers are good here.”

The combination of a prestigious university making a major investment of resources and top leadership in stem cell research, and a state where significant funding is being committed to the effort, has proved to be a powerful attraction for some of the best young minds in the field.

“I am extremely pleased with our ability to recruit these faculty to UCLA,” said Owen Witte, M.D., professor of microbiology, immunology and molecular genetics in the UCLA College and director of the UCLA Institute for Stem Cell Biology and Medicine. “They are five top people from great training environments. We competed with virtually every major institution for one or another of them, and it’s gratifying that we were able to encourage them all to come here. Individually they are truly spectacular, and you can really feel the energy force of them together, and in association with other faculty.”

The UCLA Institute for Stem Cell Biology and Medicine marshals the expertise of scholars across the medical sciences, philosophy and public policy in a joint effort to unravel the mysteries of the growth and development of adult and embryonic stem cells. Their goal is to translate fundamental observations about stem cells into new and more effective ways to treat and prevent a host of formidable medical issues, including HIV, cancer and neurological disorders such as stroke, spinal cord injury, brain tumors, multiple sclerosis and genetic diseases.

UCLA is investing $20 million over five years to launch the institute. The university is positioning teams of researchers to compete for state grants created by the 2004 passage in the state of Proposition 71. Voter approval created the California Institute of Regenerative Medicine to regulate human embryonic stem cell research and provide funding at institutions throughout the state for studies in a field that is generating tremendous excitement within the scientific community.

The institute, a collaboration of the College of Letters and Science, the David Geffen School of Medicine, the Jonsson Cancer Center, and the Henry Samueli School of Engineering and Applied Science, created a dozen new faculty positions; of the first five hires, four are based in the College.

At a time when science in many quarters remains mostly the province of men, it’s also worth noting that four of the five new stem cell faculty are women.

“We set out to hire the best people for the positions we had advertised, and we were delighted to be able to find such strong scientists who also happen to be women,” said Witte. “These scientists are terrific role models for female students interested in science.”

The new stem cell faculty include:

• Amander Clark (Molecular, Cell and Developmental Biology). Clark’s lab uses human and mouse embryonic stem cells to examine fundamental mechanisms involved in the formation and function of the human egg and sperm, and in the molecules essential for early embryo development. The research has important implications for the approximately 10 percent of the population of reproductive age who are affected by infertility, since normal development of the egg and sperm is essential to prevent infertility.
• William Lowry (Molecular, Cell and Developmental Biology). Lowry investigates whether stem cells found in different tissues use similar mechanisms for self-renewal and change. Adult stem cells can be found in most major organ systems, and among their defining characteristics is the ability to replicate and differentiate. A better understanding of the process stem cells use to renew themselves could prove invaluable in the battle against certain cancers, which appear to be caused by stem cells gone awry.
• Hanna Mikkola (Molecular, Cell and Developmental Biology). Mikkola studies how the embryo makes hematopoietic (blood-forming) stem cells—one approach to determining what gives these cells the ability to self-renew. Hematopoietic stem cells have a unique ability to self-renew, and can sustain blood cell production throughout an individual’s lifetime—but they can replicate only in response to instructive signals from their micro-environment. As a result, it has not been possible to expand these cells in culture while maintaining their self-renewal ability, which limits the availability of these cells for bone marrow transplants. Mikkola is seeking to understand how these cells develop and how their self-renewal ability is established and regulated during embryogenesis.
• Kathrin Plath (Biological Chemistry, David Geffen School of Medicine at UCLA). Plath’s lab focuses on understanding how changes in the structure of chromatin are established, maintained and modified to control gene expression, cell fate and cellular identity in mammals. The chromatin processes studied by Plath are deregulated in cancer, and are likely to contribute to the abnormal gene expression patterns observed in cancer cells. Plath's group is establishing and characterizing new models to assess the role of chromatin in cancer development.
• April Pyle (Microbiology, Immunology and Molecular Genetics). During her post-doctoral fellowship, Pyle discovered key survival characteristics important for the growth of human embryonic stem cells. How these cells “make decisions” to survive, self-renew, or differentiate is not well understood. Pyle’s lab is now focused on understanding the molecular mechanisms associated with cell-fate decisions. Understanding how to improve the survival of these cells could help to facilitate genetic manipulation of cells for therapeutic benefit. Pyle’s lab is also using human embryonic stem cells as a model system to pursue a better understanding of cancer progression and human development.

Pyle said she was drawn to UCLA by the leadership and vision shown by Witte and Judith Gasson, Ph.D., director of the Jonsson Comprehensive Cancer Center and co-director of the Institute for Stem Cell Biology and Medicine. (Clark, Mikkola and Plath are members of the Jonsson Center.) Equally attractive, Pyle said, was the accomplished nature of the stem cell researchers already working at UCLA—including the other new faculty.

“I knew Owen was recruiting these individuals, and that together we would make a dynamic group,” Pyle said.

Mikkola, who, along with Plath, were the first two stem cell faculty members to come aboard, said she arrived with high expectations and has not been disappointed. “There’s such an energy to the stem cell community at UCLA,” Mikkola said. “As soon as I got here I became part of it and have already established great collaborations.”

While collaboration is seen as important in virtually every area of science, it is especially so in stem cell research for several reasons. Moving discoveries in stem cell research from the lab to the clinic where it can help patients is likely to require the expertise of multiple scientists. In addition, the field is relatively new and untapped, particularly in the area of human embryonic stem cells. Clark and Pyle bring experience working with human embryonic stem cells, and they are expected to work in that arena with the other new faculty, as well as with established faculty.

“These cells are really difficult to grow, and we’re just now beginning to understand what genes might be important in promoting their growth and survival,” explained Pyle, who has already begun collaborating with Clark and Mikkola, as well as with engineering faculty. “Just being able to discuss with experienced colleagues the day-to-day issues that come up is really important.”

In addition to the informal Friday afternoon gatherings, there are weekly stem cell working-group meetings, exchanges at the institute’s core facilities, and a twice-a-month meeting of all students, postdoctoral fellows and faculty from the stem cell laboratories, where research progress reports are given and attendees help presenters to trouble-shoot.

The interaction has been particularly great among the new faculty.

“We talk all the time about what each of us is doing,” says Lowry. “There is a lot to learn from people working in different kinds of stem cells and different model systems in general. Rather than getting wrapped up in your own world, you can apply ideas from other fields to your work and make real progress.”

With several more new faculty slots to fill in the next two years, there is a sense that the positive energy surrounding the new stem cell faculty is only the start. Just as the presence of Mikkola and Plath made it easier to recruit Clark, Pyle and Lowry, the excitement generated by the five new recruits is expected to help bring equally talented new members to fill the other slots.

“When you’re surrounded by all of these great scientists it invigorates the way you think about your own science,” said Clark. “There is a lot of excitement here and a lot of hope that we will be able to move toward new cell-based therapies and a better understanding of the basic biology of human embryo development.”