Rice bioengineering graduate students Eric Molina, Sonia Parra, Samantha Paulsen and Reid Wilson have each been selected for a Ruth L. Kirschstein National Research Service Award (NRSA) to support their investigations and training in clinical and biomedical engineering research.
NRSA fellowships are provided by the National Institutes of Health to individuals at various stages of their education to help ensure a diverse pool of highly trained scientists and engineers in specified health-related areas.
NRSA fellows are selected after rigorous peer-review and scoring of the proposed work by a panel of established and senior scientists. Awardees are provided up to five years of predoctoral support.
Modeling bone cancer
Molina is a doctoral student in Antonios Mikos’ laboratory at Rice and an M.D./Ph.D. student in the Medical Scientist Training Program (MSTP) run jointly by Rice and Baylor College of Medicine. For the past two years, Molina’s research in the Mikos group has focused on developing electrospun polymeric scaffolds to grow bone sarcoma cells to understand how the cancer grows, spreads and resists drug therapies. Mikos is Rice’s Louis Calder Professor of Bioengineering and Chemical and Biomolecular Engineering.
Molina’s NRSA fellowship from the National Cancer Institute will build on this knowledge as he studies how natural forces in the body — such as inherent stiffness of varying tissues and those that push, pull and continually flow — influence pathogenic signaling in cancer cells.
“Cancer cells, like healthy cells, are sensitive to the physical properties and forces in their environment,” Molina said. “Our electrospun scaffolds provide a mechanically tunable model to rigorously study tumor populations, local microenvironments and drug responses. We aim to create models that better reflect the pathogenic signaling and resistance mechanisms in cancer.”
Molina plans to validate the experimental model with clinical data provided by collaborators in the Texas Medical Center.
Rapid cervical precancer screening
Parra, an MSTP M.D./Ph.D. student in Rebecca Richards-Kortum’s laboratory, will use her NRSA fellowship from the National Cancer Institute to develop and test a mobile high-resolution microendoscope (HRME) system that provides minimally invasive optical screening and rapid diagnosis of cervical precancer.
After applying topical fluorescent contrast agents, the HRME’s miniature microscope and fiber-optic probe transmit subcellular images of the epithelium to a computer, which allows for a low-cost, see-and-treat approach that could eliminate the need for colposcopies, cervical biopsies and pathology services.
Cervical cancer is preventable through regular health care screenings and protections such as the HPV vaccination, said Parra, who is in her third year of graduate studies at Rice. “But limited access to screening programs, and the need for increased public education in remote areas of the United States and around the world, have produced at-risk populations.”
Parra has previously been part of a collaborative HRME screening system with researchers in the Richards-Kortum laboratory and the Department of Gynecologic Oncology at the University of Texas MD Anderson Cancer Center that involves cervical cancer screening in low-resource areas of San Salvador, El Salvador.
“The effectiveness of the HRME has yet to be evaluated in an underserved area of the United States,” Parra said. “My NRSA grant will support a new study in the Rio Grande Valley along the Texas-Mexico border.”
Richards-Kortum is Rice’s Malcolm Gillis University Professor, professor of bioengineering and of electrical and computer engineering. She also directs the Rice 360°: Institute for Global Health, which has been involved in testing the HRME in pilot studies in China.
Bioprinting multiscale vasculature
Paulsen, a fourth-year doctoral student in Assistant Professor Jordan Miller’s laboratory, received her NRSA fellowship from the National Heart, Lung and Blood Institute.
Paulsen’s research will involve the creation of vascular tissues using 3-D bioprinting of living cells to better understand the mechanical and physiological aspects of new blood vessel formation. The scope of her work involves building three-dimensional fibrin gels integrated with endothelial cells, the primary components of capillaries, with pericytes, specialized smooth-muscle cells that wrap around and interact with endothelial cells to regulate blood vessel stability and promote remodeling.
The research builds from previous investigations by Paulsen and Miller that combine 3-D bioprinting, sophisticated imaging techniques and computational testing to analyze and control patterns and critical points of development that lead to multiscale, branched vasculature in tissue.
“In addition to serving as key communicators that prompt vascular growth and healing processes, pericyte cells have direct mechanical influences,” Paulsen said. “The project also seeks to clarify how pericyte loss affects the function of small vessels and is linked to many devastating diseases such as cancer, Alzheimer’s disease and diabetic eye diseases.”
A new way to study intestinal disease
Wilson is an MSTP M.D./Ph.D. student and a fourth-year graduate student of Jane Grande-Allen, the Isabel C. Cameron Professor of Bioengineering. His NRSA fellowship from the National Institute of Diabetes and Digestive and Kidney Diseases, will involve the creation of biomaterial and tissue engineering platforms that model intestinal tissue microenvironments and disease progression.
To better understand the complexities of gastrointestinal tissues and the causes of inflammatory diseases, such as ulcerative colitis and Crohn’s disease, Wilson will grow intestinal epithelial and stromal cells in three-dimensional hydrogels designed to mimic the villi that cover the epithelial lining of the inside surface of the intestinal wall.
“There are three types of ultrathin layered tissues that make up the inner lining of the intestinal tract, called the mucosa,” Wilson said. “This project will focus on the epithelial-stromal crosstalk between the two innermost layers — the mucosal epithelium and lamina propria, and their response to external stimulus, such as the cyclic wave-like contractions, that occur during digestion with the help of the outer muscularis-mucosa layer.”
In analyzing the biomechanics of cell interaction, growth and differentiation, Wilson will expose the three-dimensional models to stimulus that mimics the complex native environments.
Ruth L. Kirschstein NRSA grants honor the late Kirschstein for her service to the National Institutes of Health, which is made up of 27 different institutional components. Kirschstein’s pioneering research led to the development of improved, safer polio vaccines. The program provides funding for qualified students in biomedical and behavioral sciences to help increase the number of well-trained scientists from underrepresented groups.