Clockwise from upper left: Hao Yuan Kueh, Florian Merkle, Robert A.J. Signer, members of the audience, Pedro Batista and Joseph T. Rodgers

Clockwise from upper left: Hao Yuan Kueh, Florian Merkle, Robert A.J. Signer, members of the audience, Pedro Batista and Joseph T. Rodgers (Photos by Cristy Lytal)

Obesity, narcolepsy, leukemia and muscle injuries have at least one thing in common: they are engaging the next generation of top stem cell scientists. Five of these scientists presented their research at the Junior Faculty Candidate Mini-symposium hosted by USC’s Department of Stem Cell Biology and Regenerative Medicine on March 3.

Hao Yuan Kueh from the California Institute of Technology introduced his research about so-called “gene circuits” in the immune systems of mammals. These complex networks of genes work together to control whether immune stem cells replicate themselves, or differentiate into more specialized cell types: macrophages and T-cells. Using a combination of experimental and mathematical approaches, Kueh has offered a potential strategy for understanding the development of normal immune cells as well as bettering human health.

“One application I’m really excited about is the potential ability to use this knowledge to precisely control cell fate in the context of regenerative medicine in cell-based therapies,” he said. “There’s a lot of excitement around using cells as either seeds for tissue regeneration, or as disease-fighting agents for cancer and other autoimmune diseases.”

Florian Merkle from Harvard University described converting stem cells into the brain cells that malfunction in two common diseases: obesity and narcolepsy. One in three Americans struggle with obesity; one in 2,000 people suffer from narcolepsy.

“Really, the reason that I embarked on these projects was because of my interest in human disease,” he said. “And the really overarching question that’s been motivating my studies is: What is it that makes certain cell types vulnerable to disease?”

Merkle created a technique for safely studying obesity and narcolepsy in the laboratory by producing three types of brain cells: hypocretin (HCRT) neurons that promote wakefulness, agouti-related peptide (AGRP) neurons that promote feeding, and pro-opiomelanocortin (POMC) neurons that inhibit feeding. In the future, this research could pave the way for correcting mutations or transplanting replacement neurons into patients with these and other diseases.

Joseph T. Rodgers from Stanford University discussed how stem cells repair and regenerate tissue, including muscle, skin and bone. Injury activates nearby stem cells, and also puts more distant stem cells on alert, preparing the entire body to help with repair if needed.

“In an injured animal, I like to think this is a time when the animal is figuring out exactly what got injured and what needs to be repaired,” he said.

Rodgers has identified some of the key molecular signals that put these stem cells on alert — including a protein called hepatocyte growth factor (HGF), which could potentially be injected into patients to stimulate wound healing.

Robert A.J. Signer from the University of Texas, Southwestern, described an important difference between blood-forming or hematopoietic stem cells (HSCs) and partially or fully differentiated blood cells. Individual HSCs synthesize far less protein than their more differentiated counterparts. Subtle changes to this level of protein synthesis can promote or prevent aging and diseases, including leukemia, anemia and bone marrow failure.

“This could begin to totally change the way that we understand gene expression and the regulation of stem cell function, regenerative activity and cancer development,” he said.

Pedro Batista from Stanford University began his talk by declaring his passion for messenger RNA (mRNA), which carries genetic information from DNA to the cell’s protein-making machinery. Much of this mRNA has been chemically modified by a molecule called “N6-methly-adenosine (m6A).” Although much study has focused on a similar modification to DNA, little is known about the role of m6A modification to RNA. Batista has made inroads into the mystery by finding that m6A enables stem cells to differentiate into specific cell types, and prevents tumor formation.

“m6A enforces the transience of genetic information,” he said, “helping cells to forget the past and thereby embrace the future.”

Andy McMahon, chair of the Department of Stem Cell Biology and Regenerative Medicine, concluded the day by offering his enthusiastic thanks to these top candidates for junior faculty positions at USC.

“It’s a real treat to have five individuals of the caliber of the five that are visiting,” he said. “It was an excellent series of very diverse talks.”

by Cristy Lytal