TAMU Times’ Blair Williamson reports that the Texas A&M Health Science Center (TAMHSC) Institute of Biosciences and Technology (IBT) in Houston is establishing a new Center for Epigenetics & Disease Prevention (CEDP) with support from the Chancellor’s Research Initiative (CRI).
The CEDP, along with collaborators from across The Texas A&M University System, is poised to transform health care by shifting the standard model of diseases prevention through an innovative “field-to-clinic” initiative. The projected new era of preventive medicine would integrate nutrition, chemistry and medicine to radically change the way cancer, metabolic disorders like diabetes and chronic conditions like cardiovascular disease are addressed by medical systems. Researchers in the field are focused on developing preventive treatments and pharmaceutical agents using beneficial compounds naturally found in food.
“This initiative brings together the A&M System’s best and brightest researchers, with expertise in agriculture, nutrition and medicine to form a diverse and highly collaborative team intent on developing revolutionary disease prevention solutions that will impact generations to come,” says John Sharp, chancellor of The Texas A&M University System, in the TAMU Times release.
The multidisciplinary and cross-institutional team spearheading the novel field-to-clinic project is focusing on identification of phytochemicals — naturally-occurring plant compounds — in whole foods that inhibit disease or have other preventive qualities beneficial to humans and animals. Once identified, these compounds will be standardized in quality-controlled, large-scale production to prepare for human clinical trials. TAMU Times reports that the CRI has invested $9 million in the field-to-clinic enterprise, with funding to recruit new faculty members, and to forge interdisciplinary ties across the system, such as with Texas A&M AgriLife Research.
“Such collaborations reinforce our commitment to the One Health initiative, which emphasizes the link between humans, animals and plants,” says Texas A&M University president R. Bowen Loftin, Ph.D. “The opportunities currently in place across the university and system make this the right time for Texas A&M to establish itself as a world leader working at the interface of diet, epigenetics and disease prevention.”
To lead the CEDP, the IBT has recruited Roderick H. Dashwood, Ph.D., a world-renowned expert in dietary cancer prevention and epigenetics (the “software that runs the human genome”) — a research field that investigates alterations in gene expression caused by mechanisms other than changes in DNA sequence. Dr. Dashwood comes to TAMHSC from the Linus Pauling Institute at Oregon State University where he served as director of the Cancer Chemoprotection Program. He also will hold a faculty appointment with Texas A&M AgriLife Research, with an adjunct appointment in the Department of Clinical Cancer Prevention at MD Anderson Cancer Center.
Dr. Dashwood’s current research focus is on genetic and epigenetic mechanisms in cancer development. The genetic basis of cancer is studied through cultured human cancer cells and whole animal approaches, including transgenic and knockout models. These models are employed to examine changes in oncogenes and tumor suppressors (e.g., K-ras, catenin, APC) and the influence of chemoprotective agents and anticancer drug candidates. The epigenetic basis of cancer is studied through work on histone deacetylase (HDAC) inhibitors and changes in protein acetylation in both cancer cells and normal cells treated with dietary agents/anticancer drug candidates. Sulforaphane from broccoli, garlic organosulfur and organoselenium compounds and a short-chain fatty acid derived from gut fermentation of dietary fiber (butyrate) inhibit HDAC activity in human cancer cells and trigger growth arrest/apoptosis. The molecular mechanisms are pursued. To translate this work to humans, HDACs and protein acetylation changes are being examined in volunteers undergoing screening colonoscopy exams.
The focus of the CEDP on epigenetics and disease prevention is particularly innovative and exciting, says Dr. Dashwood on his TAMU bio-page. “Epigenetics research is at the frontier of biomedical research, and the epigenome is one of the most promising targets for disease prevention.”
Epigenetics and disease prevention are in the vanguard of contemporary biomedical research, the epigenome being one of the most promising targets for disease prevention. The CDEP notes that unlike the genome, the epigenome is quite “plastic”, and can be (re)programmed by environmental and dietary agents to enhance human health and prevent disease. Epigenetics research dealing with gene expression changes that can be impacted by environmental, dietary, and lifestyle factors is a major focus area.
Epigenetic work considers the mechanisms by which whole foods, isolated constituents, and metabolites act as modifiers of gene expression and dovetails experiments at the interface of protein acetylation (histone and non-histone changes), DNA methylation, and non-coding RNAs (miRNAs, lincRNAs, etc.). This “epigenetic trinity” can be affected by isothiocyanates from cruciferous vegetables (eg: broccoli other members of the cabbage family), garlic organosulfur and organoselenium compounds, shortchain fatty acids derived from gut fermentation of dietary fiber (e.g., butyrate), and phytochemicals in spinach. Of particular mechanistic interest is the growth arrest, autophagy, and/or apoptosis that occur in cancer cells, with less marked changes in normal cells.
“The addition of Dr. Dashwood to the preeminent team of scientists across Texas A&M and partnering entities in the Texas Medical Center in Houston positions the Texas A&M Institute for Biosciences and Technology to be a global frontrunner in disease prevention,” says Dr. Brett P. Giroir, M.D., who currently serves as vice chancellor for strategic initiatives for the Texas A&M System and will assume the role of interim executive vice president of TAMHSC on Oct. 1.
Dr. Dashwood will oversee efforts to initially isolate beneficial compounds and then formulate them with the help of the National Center for Therapeutics Manufacturing (NCTM) so that they can be administered in the type of controlled method necessary for clinical trials. Researchers from the College of Agriculture and Life Sciences and the College of Science will help separate and synthesize derivatives of beneficial phytochemicals. Preclinical animal model studies will then be performed in collaboration with researchers at the College of Veterinary Medicine and Biomedical Sciences. They will work with the Texas Institute for Preclinical Studies (TIPS) to screen these compounds in naturally occurring and genetically engineered mice supplied by the Texas Institute for Genomic Medicine (TIGM).
Dr. Dashwood’s lab examines genetic and epigenetic changes in cancer. Lab members come from diverse backgrounds, including molecular toxicology, biochemistry, cell biology, genetics, pharmacology, pharmacy, and nutrition. The research tools are equally diverse, encompassing primary human colon cancers and patient-matched controls, cultured human colon cancer cells, preclinical models, and mechanistic studies at the molecular level. Genetic aspects focus on mutational events in oncogenes and tumor suppressors, and the beneficial versus deleterious actions of diet and lifestyle factors.
TAMU epigenetic researchers will use the Gulf Coast Consortium for Chemical Genomics screening center at the IBT comprised of high-throughput robotic workstations to evaluate the compounds and look for new “hits” for cancer prevention. The majority of the workstations in this screening center were funded by a $12 million grant from the Cancer Prevention Research Institute of Texas awarded to Pete Davies, M.D., Ph.D. , director of IBT’s Center for Translational Cancer Research and IBT associate director. Texas A&M has also invested an additional $1 million for an additional workstation to study other non-cancer diseases.
The Texas A&M Health Science Center Houston campus, strategically located in the Texas Medical Center, conducts world-class research and trains the next generation of health care professionals and scientists. As part of the Houston campus, the Institute of Biosciences and Technology provides a bridge between TAMSHC investigators and scientists across the Texas Medical Center and the growing biotechnology sector in Houston. It encourages its scientists to transfer discoveries made in their laboratories to the marketplace so the institute’s research results can help people. Faculty members work with biotech companies. Many licensing agreements are based on the institute’s research, and several new companies have been established.
Once identified, the best compounds will then go to the Texas Medical Center for testing in human clinical trials.
“Recruitment of Dr. Dashwood will connect the research activities across the state in new and exciting ways,” says Dr. Cheryl Walker, Ph.D., director of the IBT. “Scientific advances in nutrition, agriculture and chemistry that are being made in College Station now will be rapidly translated into clinical trials in the Texas Medical Center to prevent cancer and many other diseases.”
While the IBT will house Dr. Dashwood and the new center, significant contributions to this enterprise come from across the A&M System, including Texas A&M University System Office of the Chancellor; Texas A&M University Office of the Provost and Vice President for Research; Texas A&M Health Science Center and its College of Medicine; College of Veterinary Medicine and Biomedical Sciences; College of Science; College of Agriculture and Life Sciences; and Texas A&M AgriLife Research.
In September 1997, the Texas A&M System Board of Regents approved organization of the health-related entities throughout the A&M System into one university — Texas A&M Health Science Center, which officially began operation on Sept. 1, 1999. Original academic units in the consolidation included College of Medicine, Baylor College of Dentistry, Institute of Biosciences and Technology, the then-proposed School of Rural Public Health and School of Graduate Studies. Located on the Texas A&M University-Kingsville campus, the Irma Lerma Rangel College of Pharmacy joined TAMHSC in 2006, and the College of Nursing opened in 2008. On July 15, 2013, TAMHSC transitioned to become a unit of Texas A&M University.
The Houston campus of the Texas A&M Health Science Center College of Medicine is located in the world renowned Texas Medical Center, the largest medical complex in the world and home to 47 institutions, including 13 hospitals and two specialty institutions, three medical schools, four nursing schools, and schools of dentistry, public health, pharmacy, and other health-related practices. It receives over five million annual patient visits, including over ten thousand international patients.
A wide variety of clinical elective rotations are also offered at affiliated institutions: MD Anderson Cancer Center, The Methodist Hospital, St. Luke’s Episcopal Hospital, St. Joseph’s Medical Center, and Memorial Hermann Southwest Hospital. Institutional, inter-institutional, and city-wide conferences are held on a regular basis for multiple specialties and provide numerous educational opportunities for students, physicians, scientists and other health care professionals.
In addition to numerous clinical and educational activities, , The College of Medicine and Institute of Biosciences and Technology provides a bridge between the Texas A&M University System scientists and other institutions’ researchers working in the Texas Medical Center and in the growing biotechnology research community in Houston. Research opportunities for students and residents are available throughout the Texas A&M Health Science Center College of Medicine Houston Campus, MD Anderson Cancer Center, and The Methodist Hospital Research Institute.
The John S. Dunn, GCC for Chemical Genomics (GCC CG) was organized in 2003 to address the growing need among Gulf Coast investigators for a centralized capability to support high throughput screening technologies. Many Gulf Coast institution research laboratories were engaged in screening projects but they were generally too small to be effective. To reduce the duplication of effort and to expand the screening capabilities, the GCC CG was organized as a research consortium to bring together scientists interested in this area of research with the aim of developing an inter-institutional academic drug discovery program.
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The John S. Dunn, GCC for Chemical Genomics
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