On February 9, 2015, a physiology professor, Rajini Rao, Ph.D, at Johns Hopkins University School of Medicine announced his research group’s findings through the journal Nature Communications regarding the problems with a protein involved in cargo transport within the cells of people with certain forms of autism and people with a deadly form of brain cancer. The research involved a protein called NHE9 which is on the surface of endosomes (“cargo carriers”) that regulate the delivery of and removal of important proteins from cells. The research suggests that drugs developed to target NHE9 could help fight the most common and deadly form of brain cancer, glioblastoma.
Dr. Rao’s team first studied cargo transport inside the cells of patients with autism. The endosomes’ function is to carry new proteins to certain areas throughout the cell and remove old proteins for destruction. The research found that “autism-associated defects in the protein NHE9 cause this protein to clog the leaks leaving the endosomes too acidic and making them race to remove cargo from the cell membrane” thus destroying the protein too soon. The acidity level inside the endosomes is key to the speed of the transport of proteins in and leaks out.
Next in the research regarding NHE9, the team researched through patient databases and found that elevated levels of NHE9 are associated with “resistance to radiation, chemotherapy and poorer prognosis for patients with glioblastoma.” Dr. Rao then teamed up with a neurosurgeon at Johns Hopkins, Alfredo Quinones-Hinojosa, M.D., to examine NHE9 in the tumor cells from several patients. Research found that the cells with the most NHE9 travelled fastest when placed on a “surface mimicking the brain” suggesting high odds of metastasis. This theory was confirmed when cells manipulated to have low or high levels of NHE9 were transplanted into the brains of mice.
Further studies revealed that in contrast to autism, NHE9 is overactive in brain cancer. The result is the endosomes leak too much and the endosome becomes too alkaline which causes “cancer-promoting cargo” to stay on the cell surface too long. Dr. Quinones-Hinojosa stated that the research results give researchers a better idea of what to target to make glioblastoma “less aggressive and devastating.”