The collaborative effort by UT Southwestern, Case Western Reserve University, and the University of Kentucky identified an enzyme named 15-PGDH that regulates tissue regeneration in multiple organs. By blocking 15-PGDH in mice with the newly discovered molecule, SW033291, the researchers found that they can rescue damaged bone marrow, liver tissue, and colon tissue. Tissue regeneration is important to recovery from injury, disease, and certain medical treatments.
"Patients undergoing bone marrow transplants and patients with colitis may benefit from this approach," said co-author Dr. James K. Willson, Associate Dean of Oncology Programs, Director of the Harold C. Simmons Comprehensive Cancer Center, Professor of Internal Medicine, and holder of The Lisa K. Simmons Distinguished Chair in Comprehensive Oncology. "We propose that SW033291 will be useful in accelerating recovery of bone marrow cells following a bone marrow transplant and may also be a treatment for colitis."
Bone marrow transplants are a common treatment for leukemia patients, among others. According to the National Cancer Institute, it is estimated that during 2015 there will be 54,270 new cases of leukemia and an estimated 24,450 people will die of this disease.
The study is published in the journal Science.
Prostaglandin, a hormone-like fatty acid, is a key factor in chronic infections and cancer.
"These inhibitors increase prostaglandin levels in a variety of tissues. For this reason, they appear to help the healing process in at least the intestines, liver, and bone marrow. We are hopeful that inhibiting 15-PGDH represents a general strategy to promote tissue repair," said co-author Dr. Joseph Ready, Professor of Biochemistry and member of the Simmons Cancer Center.
The new SW033291 molecule works by targeting a 15-PGDH-regulated pathway of bone marrow regeneration in which increased bone marrow prostaglandin drives the production of hematopoietic cytokines by CD45-positive marrow cells.
The UT Southwestern team discovered the molecule in collaboration with the University of Kentucky and long-time research collaborators at Case Western Reserve: Dr. Sanford Markowitz, Professor of Hematology and Oncology, and head of the Cancer Genetics Program there; and Dr. Stanton Gerson, Professor of Hematology and Oncology, and Director of the Case Comprehensive Cancer Center. Dr. Yongyou Zhang, a Case Western Reserve research associate, was a lead author on the study.
"It's been a pleasure to be involved in another example of a collaborative, multi-disciplinary team advancing the results of a high-throughput, chemical library screen toward a therapeutic possibility for an unmet medical need," said co-author Dr. Bruce Posner, Associate Professor of Biochemistry at UT Southwestern and member of the Simmons Cancer Center.
Other UT Southwestern researchers involved include Dr. Noelle Williams, Associate Professor of Biochemistry; Dr. Monika Antczak, research scientist in the Department of Biochemistry; and Dr. Shuguang Wei, senior research scientist in the Department of Biochemistry.
This work was funded by grants from the National Institutes of Health, the Scholar Innovator Award from the Harrington Discovery Institute, grants from the Marguerite Wilson Foundation, Inje University, NRF-MSIP of Korea, the Welch Foundation, Cancer Prevention and Research Institute of Texas (CPRIT), and gifts from the Leonard and Joan Horvitz Foundation, and the Richard Horvitz and Erica Hartman-Horvitz Foundation.
UT Southwestern's Harold C. Simmons Comprehensive Cancer Center is the only National Cancer Institute-designated cancer center in North Texas and one of just 68 NCI-designated cancer centers in the nation. The Harold C. Simmons Comprehensive Cancer Center includes 13 major cancer care programs with a focus on treating the whole patient with innovative treatments, while fostering groundbreaking basic research that has the potential to improve patient care and prevention of cancer worldwide. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians.
In addition, the Simmons Cancer Center is among only 30 U.S. cancer research centers to be named a National Clinical Trials Network Lead Academic Site, a prestigious new designation by the NCI, and the only Cancer Center in North Texas to be so designated. The designation and associated funding is designed to bolster the cancer center's clinical cancer research for adults and to provide patients access to cancer research trials sponsored by the NCI, where promising new drugs often are tested.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to about 92,000 hospitalized patients and oversee approximately 2.1 million outpatient visits a year.
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