Teams from Rice University, Texas Children’s Hospital and The Methodist Hospital Research Institute study nanobubbles, astrocytes, peroxisomal disorders and bone cancer
Nanobubble treatment for cancer patients, a study of peroxisomal disorders, the role of astrocytes in the central nervous system and a search for genetic factors in bone cancer are the focus of this year’s grants supported by the Virginia and L.E. Simmons Family Foundation Collaborative Research Fund.
These four projects will receive seed grants that go to teams of collaborators from Texas Medical Center (TMC) institutions centered at Rice University, Texas Children’s Hospital and The Methodist Hospital Research Institute (TMHRI).
The fund was formed to promote novel solutions to difficult medical problems through the combined expertise of TMC scientists, engineers and physicians who might not otherwise collaborate. This is the fifth and final year of the $3 million initiative funded by Simmons, an emeritus trustee of Rice, a trustee at Texas Children’s and a board member of TMHRI.
“One of the things I’ve been very impressed with is the level of consistency of these important, innovative proposals,” Simmons said. “The number of proposals stayed pretty steady each year, in the mid-30s, and I’m particularly pleased with how smooth the collaboration between the institutions has been.
“I have, personally, no way in the world of adequately assessing the research value or scientific technology of these projects, but we have really good outside reviewers who do that,” he said. “My interest has been in having the researchers and institutions find ways to work together. In that context, it’s been a home run.”
This year’s winners:
Nanobubbles for selective cancer therapy
Dmitri Lapotko and Malcolm Brenner are looking for faster, safer and more accurate ways to manipulate the components of human tissue grafts for cancer patients by using plasmonic nanobubbles to simultaneously select specific cells for gene therapy while eliminating others.
Plasmonic nanobubbles form and burst in a fraction of a second when a gold nanoparticle targeted to a specific type of cell is heated. The size of the plasmonic nanobubbles dictates whether the cell is destroyed or its wall is temporarily opened to allow drugs to enter. A recent development allows the researchers to target multiple types of cells for treatment or destruction and activate the plasmonic nanobubbles with a pulse of laser light.
Lapotko is a faculty fellow in biochemistry and cell biology and in physics and astronomy. Brenner is a professor of medicine and of pediatrics at Baylor College of Medicine (BCM) and director of the Center for Cell and Gene Therapy at BCM, Texas Children’s Hospital and The Methodist Hospital. Their co-investigator is Ekaterina Lukianova-Hleb, a research scientist at Rice.
Peroxisomal disorder treatments
Michael Wangler, assistant professor of molecular and human genetics at BCM and a pediatric geneticist at Texas Children’s Genetics Clinic, is looking for the roots of peroxisomal biogenesis disorders and associated diseases that cause seizures, intellectual impairment, blindness and hearing loss. Scientists understand a great deal about the genetic cause of peroxisomal disorders, and they have linked the genes involved to the peroxisome, a compartment of the cell involved in the body chemistry for specialized fats, protection from toxins and oxidation. However, what is missing is an understanding of how the loss of the peroxisome in these diseases causes the symptoms. Without this, patients with peroxisomal disorders like those seen by Wangler in his clinic are left without effective treatments.
The team will study peroxisomal systems in fruit flies, which have a complex brain and all the peroxisomal machinery found in humans. Studies in flies allow for sophisticated approaches to understanding genetic mechanisms. The researchers will introduce peroxisomal defects in flies using biochemical techniques pioneered at Rice by James McNew and powerful assays for understanding brain dysfunction in the laboratory of Hugo Bellen. With this data, the group can test potential treatments based on these findings and test these treatments in human cell lines from Wangler’s patients.
McNew is an associate professor of biochemistry and cell biology at Rice, and Bellen is a BCM professor, a Howard Hughes Medical Institute investigator and a researcher at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital.
What do astrocytes do?
Researchers say much is known about neurons in the brain but little is known about glial cells. These cells have long been thought of as simple structural elements but are now suspected of playing a much greater role. A team led by Benjamin Arenkiel of Texas Children’s Hospital and BCM plans to investigate the critical, and yet unknown, mechanisms of neuron-glia interactions, specifically those of the astrocyte glial cells.
Astrocytes are the most abundant glial cells in the central nervous system and have recently been identified as having roles in neural development and circuit function and formation of the blood-brain barrier. Evidence suggests astrocyte dysfunction directly contributes to neurological diseases that include autism, epilepsy, schizophrenia, amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s. The researchers want to know if there are molecularly distinct subtypes of astrocytes and will work toward a more complete picture of how they interact with neurons.
Arenkiel is an assistant professor of molecular and human genetics at BCM and at Texas Children’s Jan and Dan Duncan Neurological Research Institute. His co-investigators are Stephen Wong, the John S. Dunn Distinguished Endowed Chair in Biomedical Engineering at TMHRI, and Benjamin Deneen, an assistant professor in the Department of Neuroscience, Center for Cell and Gene Therapy at BCM.
Treatment for bone cancers
Researchers led by Brendan Lee of Texas Children’s and BCM will study chondrosarcoma, the second-most common form of malignant bone cancer. Treatment options are poor, and only about 25 percent of patients with aggressive forms of the disease survive for five years.
The team will apply state-of-the-art genetic and genomic technologies to identify the genes and pathways that are altered in this cancer. They hope this will help find its cause and contribute to possible diagnostic tests and treatments.
Lee is director of the Skeletal Dysplasia Clinic at Texas Children’s Hospital, a professor of molecular and human genetics at BCM and a Howard Hughes Medical Institute investigator. Co-investigators are Shanda Blackmon, an assistant member at TMHRI, an attending physician at The Methodist Hospital and an assistant professor of surgery at the University of Texas MD Anderson Cancer Center, and Lisa Wang, an associate professor of pediatrics at BCM and director of the osteosarcoma program at Texas Children’s Cancer Center.
The Simmons family
L.E. Simmons is president and founder of SCF Partners, an investment firm that provides management expertise to energy service companies.
Virginia Simmons is vice president of the Simmons Family Foundation, which supports religious, art and cultural organizations, education, and youth and medical associations.
For information on the Virginia and L.E. Simmons Family Foundation Collaborative Research Fund, visit www.collaborativeresearchfund.org.