5 Rice students win prestigious Kirschstein NRSA fellowships

Rice students Jason George, Roxanna Llinas, Brandon Smith, Emma Watson and Eric Yang 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.

The Kirschstein-NRSA MARC U-STAR program supports undergraduate academic and research training to help ensure that a diverse and highly trained workforce is available to assume leadership roles related to the nation’s biomedical and behavioral research agenda. The program provides funding for qualified students in biomedical and behavioral sciences to help increase the number of well-trained scientists from underrepresented groups.

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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.

Mathematical algorithms to predict levels of immune therapy

George is a fourth-year bioengineering graduate student in Professor Herbert Levine’s laboratory and a student in the Medical Scientist Training Program (MSTP), run jointly by Rice and Baylor College of Medicine.

As a member of Rice’s Center for Theoretical Biological Physics (CTBP), he has developed mathematical algorithms to score and predict genetic drivers of metastatic cancer. The fellowship will support his development of a mathematical model that optimally matches stem cell donors to patients with acute myeloid leukemia. By rigorously analyzing the effects of thymic selection on the CD8+ (cytotoxic) T cells that target and kill malignant cells, George hopes to apply the model to predict levels of patient immune reaction to donated stem cells and overall success of the treatment.

“My interests have always been in mathematical and probabilistic theory,” George said. “As a training fellowship, the NRSA award has helped me to focus my theoretical research on a clinical question that might one day improve the lives of cancer patients.”

George’s clinical adviser is Dr. Jeffrey Molldrem, professor of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center. Levine, his Rice adviser, is the Karl F. Hasselmann Professor of Bioengineering and co-director of the CTBP.

“I want to better understand from a quantitative perspective the role of malignant and immune cells during cancer progression,” George said. “My hope is that this work may eventually provide clinicians with valuable information that can be used to maximally utilize immune therapy and more aggressively attack cancer.”

Advancing human peroxisome health  

Llinas, a fourth-year biochemistry and cell biology graduate student, studies peroxisomes in Arabidopsis thaliana, a small plant, in the lab led by Bonnie Bartel, Rice’s Ralph and Dorothy Looney Professor of Biochemistry and Cell Biology.

“Although peroxisomes are vital to both plants and animals, we still lack a complete understanding of all the components involved in the creation, maintenance and function of peroxisomes,” she said. “The NRSA fellowship will allow me to contribute to our understanding of the mechanics underlying peroxisome function and may provide an avenue for advancing human peroxisome health.”

Llinas is focusing on elucidating how peroxisomes acquire the enzymes used to catalyze the reactions that support several biosythetic pathways of the cell.

“I am using a forward genetics approach to identify mutations that impact the peroxisomes’ ability to import and accumulate proteins,” she said. “I have so far isolated several mutants with altered peroxisome function and my next step is to identify the mutated gene causing the disruption and determine how the mutation is causing the disruption to ultimately inform what that gene does typically when not mutated.”

Improving early diagnosis of oral cancer

Yang, a fourth-year bioengineering graduate student enrolled in the M.D./Ph.D. program at Baylor College of Medicine, is focused on improving early diagnosis of oral cancer.

“Late diagnosis of oral cancer leads to higher mortality,” he said. “I’m developing inexpensive, automated optical-imaging instruments to help clinicians identify and manage patients with precancerous lesions to improve the early diagnosis of oral cancer.”

Yang is developing a two-step imaging process. First, high-risk areas within an oral lesion are identified using autofluorescence imaging; then a high-resolution microendoscope is used at those areas to improve diagnostic performance.

Yang works with his adviser, Rebecca Richards-Kortum, the Malcolm Gillis University Professor, professor of bioengineering and of electrical and computer engineering and director of the Rice 360° Institute for Global Health, as well as Dr. Ann Gillenwater, a head and neck surgeon at MD Anderson, and Dr. Nadarajah Vigneswaran, an oral medicine and pathology specialist at UT Dental School in Houston.

“Once I have all the components of the two-step imaging process in place, I will then test it out prospectively,” Yang said. “In particular, I want to assess whether it can help clinicians assess the risk of an oral lesion and guide biopsy location.”

Synthetic bone substitutes for bone regeneration

Smith, a fourth-year bioengineering student enrolled in MSTP, will use his NRSA fellowship to focus on synthetic bone substitutes for bone regeneration.

Calcium phosphate cements (CPC) have shown great promise for the regeneration of bone. Smith will incorporate biocompatible, glucose-based microparticles into the CPC to significantly increase the scaffold’s interconnected pore structure and allow for rapid nutrient and antibiotic delivery. The work builds from previous research in collaboration with John Jansen, a professor in biomaterials at Radboud University Nijmegen.

Smith conducts research under his adviser, Antonios Mikos, Rice’s Louis Calder Professor of Bioengineering and Chemical and Biomolecular Engineering and professor of materials science and nanoengineering.

“The challenge we face is the scaffold’s slow degradation rate, which hinders the ability for native tissue ingrowth,” Smith said. “Outcomes from this project will provide insight into how glucose-based microparticles can be used in new tissue engineering and therapeutic approaches for complex bone defects of large or unusual sizes.”

Leveraging bone tissue’s repairing nature

Watson, a third-year bioengineering graduate student enrolled in MSTP, also conducts research in Mikos’ laboratory.

She is focused on manufacturing and testing porous polymethylmethacrylate (PMMA) implants, which serve as a space holder in craniofacial reconstruction and deliver controlled release of antibiotics. Her clinical adviser is Dr. Mark Wong, an oral and maxillofacial surgeon at the University of Texas Health Science Center at Houston School of Dentistry.

The lab’s specialized PMMA implants are designed to keep a pocket for new bone open while the overlying soft tissue heals. The space maintainers are created using 3-D printed molds that allow for the creation of patient-specific devices. In later surgery, the implant is removed to make way for reconstruction of the bone using transplanted bone harvested from the patient’s own body.

“The novelty of our approach is that we leverage bone tissue’s ability to repair itself and grow tissue in vivo,” Watson said. “Because we use the patient’s own cells, new bone is cultured for up to three months to match the shape of bone we are replacing in a customized chamber that is implanted in an isolated area, such as in the rib periosteum.”

Jawbone defects are susceptible to invasion by bacteria as a result of trauma or disease, and through local soft tissues, such as nasal passages, the sinuses and the mouth.

“My research will also involved the evaluation of space maintainers and the interplay between bacteria, antibiotic delivery and the body’s immune response to bone growth, which will provide us with the information we need for tighter control of antibiotic release,” she said.

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.