Click here to read about Dr. Schimmel’s latest published work supported by NFCR
One of the most fundamental questions facing scientists today is how seemingly normal cells become cancerous. To better understand how this happens, Dr. Paul Schimmel has dedicated more than 40 years to examining the minute forms and intricate functions of molecular biology.
Dr. Schimmel, a world-renowned biophysical chemist and pioneer in translational medicine, developed the concept of expressed sequence tags in 1983, an approach employed for the Human Genome Project. During his career-long study of essential enzymes, he worked on an enzyme-directed genetic code, known as aminoacyl-tRNA synthetase (aaRS). Humans express 20 different aaRS enzymes, each playing a pivotal role in gene expression. With NFCR funding since 1994, Dr. Schimmel has advanced our understanding of the important role these essential enzymes play in defining the genetic code. Strong associations of some of these enzymes to human diseases has been revealed as well. These associations are now believed to be related to new functions of these proteins studied by Schimmel and collaborator, NFCR-supported scientist, Dr. Xiang-Lei Yang. It now appears that, with these proteins, treatable diseases include chronic and acute inflammation, neuropathy, and cancer progression and metastasis.
One aaRS, SerRS, possesses both anti-tumor and anti-metastasis properties. The scientists showed that SerRS inhibits a pro-cancer gene that triggers release of VEGF, a blood vessel formation factor. Without their own blood supply, tumors are deprived of oxygen and nutrients required for growth. In addition, they discovered that SerRS regulates many immune system-related molecules, implicating a role of SerRS in cancer metastasis.
This research is being conducted in triple negative breast cancer models and tissue samples from patients. They have discovered the expression of SerRS positively correlates with greater survival in breast cancer patients. The results also demonstrate SerRS is significantly downregulated during metastasis, suggest that SerRS is a suppressor of breast cancer and its metastasis. Similar findings of SerRS expression has been found in tissue samples of brain, esophageal, kidney (clear cell), rectal, stomach, and thyroid cancers. Their significant research may lead to novel therapeutic applications for these cancers.
Dr. Schimmel’s team discovered that one type of tRNA – TyrRS – plays an important role in platelet production and maintenance. Platelets are the tiny blood vessels responsible for forming blood clots; they are often damaged during chemotherapy and cause dangerous bleeding disorders. Dr. Schimmel’s team is developing a TyrRS-based treatment that corrects this damaging side effect.





