For more than 60 years, the Donald E. and Delia B. Baxter Foundation has supported innovative biomedical research at the Keck School of Medicine of USC, each year granting $100,000 awards to two faculty. This year, the foundation named Albert Almada, PhD, and Miller Huang, PhD, Donald E. and Delia B. Baxter Foundation Faculty Fellows. The foundation also gave $75,000 to support the Keck School’s Medical Student Summer Research fellowship program.

“We are proud to support Drs. Almada and Miller’s research, which holds great promise in developing approaches to prevent muscle loss and treat pediatric cancer,” said Katie Russell, president of the Baxter Foundation. “We are dedicated to aiding young researchers, including medical students, across California who are developing innovative treatments to improve the quality of life of individuals around the world.”

Early in their careers, new scientists require monetary support to develop preliminary data and build research programs to effectively compete for research funding. The Foundation supports researchers at this early stage so they can conduct innovative and impactful research that has strong future potential for translation into new therapies, diagnostic tools, and/or approaches to prevent disease. The Foundation is particularly interested in supporting basic laboratory research programs.

“I am confident that I will use the generous funding support from the Baxter Foundation to jump-start my research program and launch my independent career at USC,” Dr. Almada said. “We are doing basic science that has the ability to translate into people living healthier and more productive lives. The Foundation’s support is confirmation that we are on the right track. This research support gives us the freedom to do the key basic science experiments that will justify moving towards human clinical studies.”

Dr. Huang, who will use his award to investigate how changes in chromosomes may cause pediatric cancers, said, “The Baxter Foundation funding is very impactful because it’s not easy to get support for pediatric cancer research. I was able to hire more technical experts, who helped push the project along faster. It also means I don’t have to spend time applying for more funding and can focus on the research.”

Preventing age-related muscle decline

As we age, many tissues and organs, such as muscles, decline in their ability to function. Dr. Almada is researching ways to prevent or even reverse such decline.

“We’ve uncovered a new stem cell activation pathway that helps rebuild muscle,” Dr. Almada said. “If we can better understand how the pathway works, and the enzymes and vitamins that make it work, we will identify new ways, such as dietary supplements, to boost this regenerative pathway in vulnerable human populations including the elderly.”

Dr. Almada’s interest in muscle degeneration was sparked by a brother who has a rare genetic neuromuscular disease known as muscular dystrophy.

“One of the earliest biological questions that intrigued me as a child, was why my older brother’s muscle was getting weaker while I was growing stronger,” Dr. Almada said. “I watched him go from being able to walk, move, and breathe on his own to being confined to a wheelchair, needing a breathing ventilator, and losing all voluntary movement. At a young age, I decided I would use this experience as motivation to do something meaningful with my life. I chose a career in science because I truly believe my research will make a difference in the lives of the people I care about.”

After earning a PhD from the Massachusetts Institute of Technology where he worked in the laboratory of 1993 Nobel Prize winner, Dr. Phillip Sharp, and conducting post-doctoral research at Harvard University, Dr. Almada joined USC as an assistant professor.

“I chose USC because I would have the opportunity to be at a top-tier research institution on the rise and would benefit from having a joint appointment in a strong clinical—orthopaedic surgery—and a basic science—stem cell biology and regenerative medicine—department,” he said. “I am in a perfect intellectual environment to translate my basic science research into therapies that help people.”

Through his work, Dr. Almada will study why stem cells, which repair damage to muscles and organs, fail to turn on as easily or as often as we age. He discovered a critical enzyme and a key vitamin that work together to enhance stem cell activity and muscle repair, a pathway that if therapeutically manipulated could be used to treat and even prevent muscular and organ decline in humans. Such research is of critical importance, since by 2040, twenty percent of Americans will be over 65, and muscle loss and its attendant lack of mobility are major issues for the elderly.

“Our work is basic science but it could have a lot of translational impact, and it’s clear how we might be able to do that,” he said. “The key vitamin that super-charges this enzymes effect is already being studied in human clinical trials. If we could now understand the enzyme better and figure out how it works, along with the vitamin, it may help us develop an effective therapy to preserve skeletal muscle in vulnerable human populations.”

Dr. Almada’s exciting research promises to open new therapeutic avenues for helping the elderly stay fit and strong for as long as possible. He is also hopeful that his work will translate into helping people like his brother.

“This regenerative pathway is so fundamental to stem cell function,” said Dr. Almada, “that it may also help us in preventing muscle loss in patients who suffer from muscular dystrophy.”

The role of chromosomes in pediatric cancer/h2>

Most adult cancers appear to be caused by an accumulation of genetic mutations over time. Pediatric tumors must have a different cause, since children have lived a far shorter time than adults and pediatric tumors have a significantly lower mutation rate than adult tumors. Instead, large regions of DNA—called chromosomes—that encompass hundreds and even thousands of genes are frequently lost or duplicated in pediatric tumors, mimicking the effect of accumulating mutations over time in adults. Research into how chromosomal changes promote cancer has been difficult since current methods to identify mutations that cause cancer use mouse cells, and genes arranged on mouse chromosomes do not match the arrangement of genes on human chromosomes.

Dr. Huang, assistant professor in the Department of Pediatrics at Children’s Hospital Los Angeles, is addressing this issue by using his human stem cell-based model of one of the most common pediatric tumors, neuroblastoma. Neuroblastoma strikes the nerves of children. Unlike most studies that seek to determine whether individual genes cause a tumor, Dr Huang is using his neuroblastoma model to research whether changes in chromosomes play a role in causing cancer. If his hypothesis is correct, he will be able to use his model to screen for possible therapeutic targets related to the tumors containing chromosomal changes and to possibly cure them.

Neuroblastoma has a low mutation rate. The most frequently mutated gene is found in only 10 percent of neuroblastoma tumors. In contrast, chromosomes are more frequently found to either gain or lose a copy in neuroblastoma. Normally, we have two copies of each chromosome but in neuroblastoma tumors, some chromosomes have one or three copies. The most frequent chromosome change is an extra 17q, which is found in more than 70 percent of neuroblastomas—and is related to a worse prognosis.

With a bachelor’s degree in bioengineering and a minor in computer science from the University of California, Berkeley, and a PhD in molecular pathology from the University of California, San Diego, Dr. Huang is analyzing the effects of an extra 17q chromosome on tumor growth by comparing human stem cell lines that are normal and another that has an extra 17q. His team plans to identify genes on 17q that may explain how the chromosome change affects the growth and spread of a tumor, and identify the genes that such tumors express, which could serve as immunotherapy targets for neuroblastoma.

Dr. Huang will also perform a genetic screen in which each gene will be disrupted in 17q tumors and healthy non-tumor cells. Some tumor cells will die if the gene that was blocked is critical for the tumor’s survival. Screening healthy non-tumor cells will allow him to identify the genes that are critical for healthy cell survival as well. His approach will determine which genes are specific for tumor cell survival. Targeting these tumor-specific genes should minimizing side effects in individuals since healthy non-tumor cells will not be as affected.

“Our genetic screening could find possible targets to treat these tumors and spare normal cells,” Dr. Huang said. “Extra copies of chromosome 17q have been found in other tumor types such as medulloblastoma, leukemia, melanoma, and pancreatic cancer. Therefore, my findings on possible genetic vulnerabilities in neuroblastoma with an extra 17q could apply to other types of tumors—potentially leading to treatments for many types of cancer.”