Faculty from across the HSC continue the fight against cancer

Texas A&M faculty awarded more than $8.6 million from CPRIT

Six recently-funded research projects at Texas A&M look to reduce the burden of cancer in Texas
August 22, 2017

The Cancer Prevention and Research Institute of Texas (CPRIT) recently awarded grants totaling more than $8.6 million to faculty members at the Texas A&M University Health Science Center. Six total grants were awarded to faculty in the Texas A&M College of Medicine—four to faculty in the college’s Institute of Biosciences and Technology in Houston—many of which include interprofessional collaborations with faculty across the Texas A&M Health Science Center, including the College of Dentistry and School of Public Health.

“We are grateful for ongoing support from CPRIT in the fight against cancer in Texas,” said Carrie L. Byington, MD, dean of the Texas A&M College of Medicine, senior vice president of Texas A&M University Health Science Center and vice chancellor for health services at The Texas A&M University System. “As the second leading cause of death in the state, we are eager to continue searching for ways to both prevent and cure all forms of cancer. In addition to innovative research, this funding will support crucial prevention efforts as we continue the exceptional progress made in early detection of breast and cervical cancer in rural, underserved populations.”

Michael Mancini and Peter Davies
Core Facility Support Award, $5,793,075

Researchers from the Texas A&M Institute of Biosciences and Technology, Baylor College of Medicine and the Gulf Coast Consortium have established a new, highly collaborative research core facility, the Center for Advanced Microscopy and Image Informatics (CAMII), to provide cancer researchers with access to sophisticated imaging and computational resources that will enable them to address critical questions in both basic and translational cancer research. The program is led by Michael A. Mancini, PhD, professor in the Department of Molecular and Cellular Biology and academic director of the Integrated Microscopy Core at Baylor, and an adjunct professor at the Texas A&M Institute of Biosciences and Technology, and Peter J. Davies, MD, PhD, professor and director at the Texas A&M Institute of Biosciences and Technology. CPRIT funding totaling $5,793,075 will support projects addressing fundamental questions in cancer biology as well as projects whose goal is the development of new therapies for the prevention and treatment of cancer. CAMII’s advanced imaging technologies will be used both by established investigators and junior investigators to conduct studies that are targeted to the development of new therapies for many different types of cancer.

“By promoting highly collaborative and productive partnerships between experts in advanced imaging research and outstanding cancer researchers, CAMII will support CPRIT’s goal of promoting innovation in cancer research and accelerating the development of breakthroughs in the search for new ways to prevent and/or to treat cancer,” Mancini said.

David McClellan and Jane Bolin
Competitive Continuation/Expansion Award, $1,350,000

David McClellan, MD, assistant professor of family and community medicine at the Texas A&M College of Medicine, and Jane Bolin, JD, BSN, professor at the Texas A&M School of Public Health and director of the Southwest Rural Health Research Center, received a $1,350,000 grant to continue improving breast and cervical cancer screening and prevention activities in rural areas of the state.

According to data from the Texas Cancer Registry, low-income and medically underserved women residing in rural areas of Texas suffer from significantly lower survival rates associated with breast and cervical cancer, bringing prevention and care to the forefront of concern across the state. The three-year grant will allow Texas A&M to continue to provide services to women in nine Texas counties, while expanding services to eight contiguous counties, seven of which are classified rural.

Building on strengths of academic medical, nursing and public health programs, and their clinical and community partners, the program will facilitate education on, access to, and provision of breast and cervical cancer screening and diagnostic services, across the continuum of care, for low-income women in 17 largely-rural Texas counties, while providing interdisciplinary training to family physician residents, nursing and nurse practitioner students and community health workers.

“We are thrilled to be able to continue and expand on the work of our previous CPRIT grant – ensuring that low-income and underserved women in the greater Brazos Valley have access to affordable and culturally relevant screenings, diagnostics, and navigation services related to breast and cervical cancer.” Bolin said. “This project we will not only increase patient awareness, but improve cancer prevention training and practices for family medicine physicians, nurses and public health professionals.”

Robert Tsai
Early Translational Research Award, $915,000

Robert Tsai, MD, PhD, associate professor at the Texas A&M Institute of Biosciences and Technology, received a $915,000 grant for his research to develop a new, noninvasive product designed to destroy lesions in the mouth that have not yet become malignant (premalignant) but are at high risk of becoming oral cancer, which affects 24,000 Americans and results in 5,400 deaths each year.

These oral premalignant lesions are also known as leukoplakia or “white plaque.” Instead of relying on surgery or laser therapy, which is more invasive, less sustained, and less cost-effective, Tsai and team, which includes Xiaohua Liu, PhD, BE, and Yi-Shing Cheng, DDS, MS, PhD, with the Texas A&M College of Dentistry, are using the approach of chemical ablation by applying drug-containing patches to lesions in the mouth. The team plans to develop a new medicated oral patch and provide crucial evidence to support the clinical feasibility, therapeutic effectiveness, and safety of this product for treating oral premalignant lesions that are chemically induced in an animal model. Successful completion of these preclinical studies will set an important milestone that will lead to further development of this product for clinical trials and eventually for it to be used for patients in the community.

“Stopping cancer development from premalignant lesions is more cost-effective than treating full-blown cancers. The presence of oral premalignant lesions provides a golden opportunity for early detection and intervention,” Tsai said. “It is our hope that this research will bring us a novel chemical ablation product that can be used as the first line of defense against oral cancers before they are developed and be more accessible to the general public compared to surgery and laser therapy, which are often associated with severe side effects such as pain, swelling, difficulty in swallowing, hoarseness and permanent scar formation.”

Yubin Zhou
High Impact High Risk Award, $200,000

Yubin Zhou, MB, PhD, associate professor in the Center for Translational Cancer Research at the Texas A&M Institute of Biosciences and Technology, in close collaboration with Yun (Nancy) Huang, PhD, an assistant professor in the Center for Epigenetics and Disease Prevention at the Texas A&M Institute of Biosciences and Technology—who was recruited to Texas A&M in 2014 by a CPRIT grant—will utilize a $200,000 award to devise an innovative epigenome remodeling toolkit to modify the DNA bases in the human genome by harnessing the power of light.

By combining state-of-the-art optogenetics with the CRISPR/Cas9 genome editing technique, this set of tools will first act as “GPS” to navigate engineered photo-switchable proteins toward cancer-associated genomic regions, and then function as a “scalpel” to remove abnormal DNA modifications at those regions for anti-cancer intervention.  
“If successful, this technology will provide a revolutionary tool to interrogate cancer epigenetics with high precision,” Zhou said. “It will also lead to paradigm-shift advances in controlling cancer by targeting pro-oncogenic changes in the human epigenome without altering the genetic codes.”

Yi Xu
High Impact High Risk Award, $200,000

Yi Xu, PhD, associate professor at the Texas A&M Institute of Biosciences and Technology, in collaboration with Robert Chapkin, PhD, Texas A&M College of Medicine and Joseph Petrosino, PhD, Baylor College of Medicine, received a $200,000 grant for her work to understand how intestinal microbes play important roles in the development of colorectal cancer.

Scientists have known for decades that people infected with a subspecies of the bacterium subspecies Streptococcus gallolyticus are more likely to have colorectal cancer, however it is not known whether S. gallolyticus plays an active “driver” role or simply prefers to grow in the tumor environment. Using multiple experimental approaches, Xu’s group demonstrated for the first time that S. gallolyticus actively promotes the development of colorectal cancer. This exciting discovery is an important breakthrough in understanding the connection between S. gallolyticus and colorectal cancer. The team is currently focused on understanding how precisely S. gallolyticus promotes the development of colorectal cancer, and what bacterial and host factors are involved. These bacterial and host factors can be attractive targets for developing new strategies to better prevent and treat colorectal cancer.

“The importance of microbes opens a door to develop novel preventive and therapeutic strategies that incorporate the microbial characteristics of the individuals,” Xu said. “The strong clinical association between S. gallolyticus and colorectal cancer and its active promoting role in the development of colorectal cancer makes S. gallolyticus an attractive microbial target.”

Phillip West
High Impact High Risk Award, $199,795

Phillip West, PhD, assistant professor in the Department of Microbial Pathogenesis and Immunology at the Texas A&M College of Medicine, received a $199,795 grant to investigate how mitochondrial DNA instability enhances melanoma growth. Like the cell nucleus, mitochondria contain DNA that can be damaged by environmental exposures, which may increase cancer risk. One such exposure, ultraviolet radiation, is a major risk factor of melanoma, as it can induce both nuclear and mitochondrial DNA instability. Various reports have documented changes in mitochondrial DNA integrity in human melanoma, suggesting an important role for this process in this aggressive skin cancer.

“A collaborative effort between my research group and two labs at Yale School of Medicine and UT Southwestern Medical Center has revealed that mitochondrial DNA instability can augment tumor growth in an animal model that closely recapitulates human melanoma,” West said. “We have uncovered unique metabolic and immune signatures in melanomas from animals exhibiting mitochondrial DNA instability. Therefore, the overall goal of our proposal is to further characterize these signatures to define how mitochondrial DNA instability and its downstream effects suppress anti-tumor immunity to potentiate melanoma growth. Our research will provide insight into unique roles for mitochondria in cancer, and may support the development of novel therapies that target these pathways in melanoma and other human malignancies.”

CPRIT awarded 60 grants, totaling more than $102 million, in its latest round of funding for cancer prevention programs. In 2007, Texas voters approved a constitutional amendment to establish CPRIT with $3 billion in bonds. Since 2009, CPRIT has presented 1,189 grants totaling more than $1.89 billion to support cancer research, product development and prevention programs, and has attracted more than 135 distinguished cancer researchers to Texas.

— Holly Shive

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