UCLA stem cell researchers receive three out of seven awards for genomic projects on autism, blood and overgrowth syndrome

Three out of seven grants recently awarded to stem cell scientists in California have gone to researchers at the Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. The funding will support research that seeks to better understand the basic biological functions of diseases through genomic analysis—a process by which researchers analyze and interpret multiple, complex data sets of information gathered from DNA. The ultimate goal of this research is to create targeted stem cell therapies for diseases linked to genetic mutations such as autism, leukemia and human overgrowth syndrome. The three UCLA-led projects total nearly $5 million in funding over three years.

Autism

One of the funded projects is headed by Daniel Geschwind, M.D., Ph.D., professor of neurology and director of the UCLA Center of Autism Research and Treatment, whose research focuses on understanding the genetic causes of neurological diseases such as autism. The award will allow Geschwind and his team to examine a very large number of stem cell lines created from people with autism spectrum disorders caused by several known mutations. The stem cells Geschwind will examine are called induced pluripotent stem cells, otherwise known as iPSC; these types of stem cells are similar to human embryonic stem cells in that both cell types have the unique ability to self-renew and have the flexibility to become any cell in the human body. However, iPSCs are generated by reprogramming skin or blood cells and do not require an embryo. Geschwind will collaborate with Dr. Sergiu Pasca at Stanford to study the cells in the laboratory using a ‘disease-in-a-dish’ model, whereby the stem cells are turned into brain cells that simulate the 3-D nature of brain cells inside a human. They then examine these cells to determine the mechanisms by which certain genetic mutations lead to abnormal brain function and ultimately result in autism spectrum disorder.

“Acquiring quality information and insight from the large amounts of data associated with scientific discovery is vital to moving this research forward in a meaningful way,” said Geschwind. “I am very pleased to receive funding for this work and I appreciate the collaborative nature of the overall program as well.”

Blood Formation & Leukemia

Gay Crooks, M.B.B.S, co-director of the Stem Cell Center and professor of pathology and laboratory medicine, pediatrics, and orthopedic surgery, received an award, in collaboration with Hanna Mikkola, M.D., Ph.D., associate professor of molecular, cell and developmental biology, and Yi Xing, Ph.D., associate professor in the department of microbiology, immunology and molecular genetics. The three investigators will collaborate on studies to map how genes control the development of human blood cells. The team will isolate a range of cell types, from the most primitive or early stage stem cells to the many diverse blood cells produced by the stem cells, and then perform genomic analysis to understand how the gene networks function together to control normal blood formation during life. These studies will also provide the knowledge to generate blood from pluripotent stem cells and to understand how leukemia develops when genes become mutated.

Overgrowth Syndrome

Another award went to Guoping Fan, Ph.D., professor in the Department of Human Genetics, to study embryonic stem cells from humans and mice, which are engineered to contain genetic mutations that cause Human Overgrowth Syndrome—a class of diseases characterized by abnormal increase in the size of the body or a body part and, in some cases, intellectual disability. Using the stem cells, Fan and his team will produce brain cells, connective tissue cells and bone cells, all of which play a role in Human Overgrowth Syndrome. By using genomic analysis to look at how the genes function in the Human Overgrowth Syndrome cells, Fan will achieve a better understanding of the molecular and cellular basis of the disease.

The funding comes from a program backed by California’s Stem Cell Agency, CIRM. The program, headed by the Stanford/Salk Center of Excellence in Stem Cell Genomics, will distribute a total of $11.6 million in CIRM funding to collaborate with California stem cell scientists on seven different research projects that focus on using genomic analysis. The goal is to use genomic analyses to better understand how stem cells change as they grow and become different kinds of cells, and then use that knowledge to come up with new treatments for a wide variety of conditions.