Associate Professor of Pediatrics and Pathology (tenured)
Cancer Biology, Pediatrics, Haematology Oncology
Keck School of Medicine
Childrens Hospital Los Angeles
- PID1 as a novel growth inhibitor in brain tumors and cancer
- The molecular mechanism of PID1 in health and disease
- Molecular mechanisms in brain cancers: medulloblastomas, gliomas/glioblastomas, atypical teratoid rhabdoid tumors (ATRT)
Research OverviewBrain tumors are the most common cause of cancer-related death in children and thus, constitute an unmet need. I believe that better cancer therapy can only come from improved understanding of the molecular mechanisms driving growth of tumors. As a physician-scientist specializing in pediatric neuro-oncology and studying molecular mechanisms in their biology, my clinical work and laboratory research are therefore well aligned. Our laboratory strives to better understand the biology of brain tumors and thus contribute to development of novel treatments based on tumor biology.
Not long ago we came across a little-known gene called PID1 (Phosphotyrosine Interaction Domain containing 1; also called NYGGF4), which surfaced in a colleague’s microarray dataset as one of the genes that was highly correlated with survival of children with medulloblastoma. Online tools revealed that mRNA of PID1 was also highly correlated with survival in gliomas, such that higher PID1 mRNA level correlated with longer survival, leading us to test its effect in culture: we found remarkable inhibitory effects on growth of three types of brain tumor cell lines: medulloblastomas, glioblastomas, and atypical teratoid rhabdoid (ATRT) tumors. This work was published in Clinical Cancer Research in 2014 (Erdreich-Epstein et al) and was the first peer-reviewed publication to link PID1 to cancer. This work suggested that PID1 is a novel candidate tumor suppressor-like gene.
Not much is known about PID1 to date, with only about 25 peer reviewed papers published on it. Other than its effects in brain tumors, PID1 has mostly been studied in adipocytes and muscle cells. It is known as an inhibitor of insulin receptor signaling and thought to play a role in insulin resistance in obesity. PID1 strongly inhibits mitochondrial function and is known to directly bind to the Low Density lipoprotein receptor-related Protein 1, LRP1, although the function of this interaction remains unknown. PID1 has also been linked to Alzheimer’s disease, although here too, its function is not clear. Clearly, the molecular mechanism by which PID1 functions and a link to explain its effect in these diverse conditions remains unknown.
Interesting and profound early data in our lab now suggest that PID1 has a central role in a number of important biological processes. As a result, most of the effort of our laboratory is directed toward understanding the function and molecular mechanism of PID1, using in vitro and in vivo approaches, with a focus on brain tumor biology. We anticipate to make profound discoveries in this field in the coming years.