• May 2021

    Translational research fuels discovery at Baylor Scott & White Research Institute

Baylor Scott & White Research Institute (BSWRI) is well known for its diverse research portfolio. The program actively maintains nearly 2,000 active and enrolling projects across more than 50 medical specialties each year, including initiatives supported by its translational research program. The program is focused on driving innovation by working with clinical teams across the Baylor Scott & White Health System to develop new medicines and diagnostic tests. The translational research team’s approach to discovery of “bench-to-bedside- and- back-to-bench” allows BSWRI to continue to be a major contributor to advancements in medical science.

Gerard Zurawski, PhD, an investigator with BSWRI, describes the research environment. “We have multiple research teams spanning a range of disciplines. Our team develops vaccines, and our colleagues maintain research programs in metabolomics, islet cell transplantation, and cellular immunotherapy, just to name a few. What links us together is our focus on making discoveries that can directly help patients.”

The BSWRI translational research program is co-directed by Dr. Zurawski, along with Teodoro Bottiglieri, PhD. Their combined work is accelerating progress toward novel therapeutic and diagnostic tools.

Immunotherapy and vaccine development at BSWRI

Dr. Zurawski was recruited to the Baylor Institute for Immunology Research in 2004 to develop dendritic cell immunotherapies. The immunotherapy research team was advised by Dr. Ralph Steinman, who went on to win the 2011 Nobel Prize for discovering dendritic cells. The immunology and cellular therapy expertise they cultivated has led to the development of vaccine technologies and to the establishment of the current Good Manufacturing Practices (cGMP)-compliant cell manufacturing facility at BSWRI. This FDA-regulated facility develops specialty cellular therapies for clinical trials and engages in research to improve the quality of cellular therapies, including chimeric antigen receptor (CAR)-T cells. As one of the few medical centers nationwide with on-site cGMP-compliant manufacturing, BSWRI attracts leading-edge clinical trial collaborations in the rapidly accelerating domain of cellular immunotherapy.

Dr. Zurawski’s current research program is focused on developing novel vaccines against cancer and infectious diseases such as HIV, hepatitis C, COVID-19, and tuberculosis. The work is in various stages of the pipeline, with publications and patents for the fundamental technologies and clinical trials in development. These projects include the creation of novel vaccines based on dendritic cell targeting technology that have advanced into early phase clinical trials for the prevention of infection against HIV-1, early-stage work on therapies for head and neck and other cancers caused by previous HPV infection, and work currently advancing to the manufacturing stage for a therapy for HIV-1-infected people and the prevention of infection by SARS-Co-V2. Thanks to funding from the National Institutes of Health (NIH) and a powerful collaboration with Dr. Yves Lévy’s team at INSERM, the French equivalent of the NIH, the seeds of innovation are growing into viable products. Dr. Zurawski says, “We have a new vaccine for HPV-elicited cancers, which we developed from the conceptual stage and is now ready for human testing. We also have a vaccine for HIV that is starting in clinical trials. Our vaccine projects have been steadily gaining momentum through more than a decade of discovery research and preclinical testing. It is exciting to see these research innovations develop fully, and we are pleased to hold a share of the intellectual property on such important advances.”

Metabolomics research

Dr. Bottiglieri is the director for metabolic disease research at BSWRI. His research team specializes in metabolomic biomarker identification for neurological diseases and metabolic deficiencies. Metabolomics is the study of how small molecules, such as hormones, signaling molecules, and metabolic pathway intermediates, can provide insight into the regulatory processes that become disrupted by disease. His team takes a dual approach to their work, with part of the laboratory operating as a CAP/CLIA-certified analytical laboratory for clinical diagnostics and the other part engaging in metabolomic discovery science. They use targeted and untargeted mass spectrometry techniques, which identify small molecular weight biomarkers in biological fluids and tissues. The team’s work is supported by institutions like the NIH, as well as philanthropic organizations. Two of their current projects funded through the Aging Mind Foundation in Dallas and the BvB Dallas Foundation are focused on finding the causes of Alzheimer’s disease and other dementias. According to Dr. Bottiglieri, “Our goals are to develop new insights that will become the next generation of clinical diagnostic and prognostic biomarkers and to identify novel therapeutic strategies. Our laboratory is using the latest technologies for advanced metabolomic analysis, making us an excellent collaborator for clinical trials and other research initiatives.”

Metabolomics is just one of several advanced high-throughput technologies that can provide a comprehensive picture of the changes caused by disease. Together with genomics and proteomics, these “omics” technologies can offer complementary insights into complex diseases.

Research infrastructure

BSWRI centralizes the research infrastructure across the Baylor Scott & White Health System and provides regulatory support, administrative resources, integrated information technology solutions, and laboratory staffing services for a range of research applications. BSWRI has a network of 1,000 research staff and investigators, and resources for genomics, biostatistics, flow cytometry, metabolomics, biosafety level-2 (BSL-2) pathogen handling, and cGMP-compliant cell manufacturing.

Additional projects Dr. Zurawski and Dr. Bottiglieri are leading through the Translational Research Program for BSWH teams, include:

  • Two studies in collaboration with the transplant team at Baylor University Medical Center:
    1. A checkpoint inhibitor antibody for therapy and prevention of transplant rejection, with initial trials focused on the prevention of Graft versus Host Disease following stem cell transplant therapy for certain advanced cancers.
    2. A longitudinal Profiling of Plasma and Urine Metabolites During Liver Regeneration in Living Liver Donors.
  • A study in collaboration with the BSWH Health & Wellness Center titled “Blood biomarkers & Identifying a cardiorenal protective diet in a lower income population with chronic kidney disease at risk for cardiovascular disease.”
  • A study in collaboration with the BSW Institute for Rehabilitation titled, “Linking biomarkers with healthy lifestyle outcomes after stroke.”