A $1 million grant from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health (NIH), will boost stem cell research at City of Hope. The funds come from the American Recovery and Reinvestment Act of 2009.

Yanhong Shi, Ph.D., associate professor in the Department of Neurosciences, obtained the grant, which she is using to find new ways of making induced pluripotent stem cells, or iPS cells.

Yanhong Shi (Photo by Darrin S. Joy)

Scientists make iPS cells by coaxing mature cells into behaving just like embryonic stem cells. Scientists believe embryonic stem cells have the potential to cure many diseases including cancer, diabetes and neurological diseases such as multiple sclerosis and Alzheimer’s disease, making them a rich area for research. Embryonic stem cells are the most primitive of cells, giving rise to all other cell types as the body grows and matures, so scientists may be able to manipulate them to replace diseased tissue. But research using embryonic cells can be controversial.

IPS cells may provide a source of stem cells with all of the potential benefits of embryonic stem cells while avoiding accompanying political issues. Also, iPS cells may be made from cells taken directly from the patients in treatment, so they would match the tissue type affected by diseases. That might make the cells more effective and targeted in treating that disease.

Today, to change adult cells into iPS cells, researchers transfer key genes into them; however, the process is inefficient and potentially risky. The transferred genes must insert themselves into the receiving cells’ DNA, and the intrusion might accidentally — and harmfully — disrupt the cells’ normal genetic processes. Also, the transferred genes might run wild and cause the iPS cells to begin forming partial new organs or cancerous tumors.

To overcome these possible problems, Shi and postdoctoral fellows Wendong Li, Ph.D., and George Sun, Ph.D., both in neurosciences, aim to improve the efficiency of gene transfer and find small molecules that can push mature cells into becoming iPS cells without using gene transfer at all.

“If we can find compounds that avoid the problems involved with the current process, we can open doors to new patient therapies,” Shi said. A more efficient means of generating iPS cells also would help researchers understand how stem cells develop and maintain themselves, a key step in moving stem cell therapies into clinical use.

Shi’s team is collaborating with David Horne, Ph.D., professor and chair of the Department of Molecular Medicine, and Richard Yip, Ph.D., director of the High Throughput Screening Core Facility, to find the molecules.

The group so far has identified a dozen promising compounds, and they are studying each to find which are most effective in helping to turn mature cells into iPS cells.

Su Yang, a student in the Irell & Manella Graduate School of Biological Sciences, also contributed to the research.