Anat Erdreich-Epstein, MD, PhD

For more information please contact Dr. Anat Epstein, [email protected]

Our laboratory studies molecular mechanisms in brain cancer. Brain tumors are the most common cause of cancer-related death in children. Better cancer therapy can only come from improved understanding of the molecular mechanisms driving growth of tumors. We strive to understand the biology of brain tumors and thus contribute to development of better treatments based on their biology.

We were the first to show that PID1 (Phosphotyrosine Interaction Domain containing 1; also called NYGGF4), thought to be an inhibitor of insulin receptor signaling, is an inhibitor of growth of a number of brain cancer cell lines (Clinical Cancer Research 2014; PMID: 24300787). These include medulloblastoma (the most common malignant brain tumor in children), gliomas and atypical teratoid rhabdoid (ATRT) tumors. We also found that patients whose medulloblastoma or glioma tumors had higher PID1 mRNA had longer survival. This work was the first peer-reviewed publication to link PID1 to cancer and suggested that PID1 is a novel candidate tumor suppressor in brain cancers. More recently we showed that PID1 mediates some of the tumor-killing effect of chemotherapy, potentially explaining the link between longer survival and higher tumor levels of PID1 mRNA (Scientific Reports, 2017; PMID:28400607).

Overall, only little else is known about PID1 to date. PID1 has mostly been studied in adipocytes and muscle cells where it is considered an inhibitor of insulin receptor signaling and thought to play a role in insulin resistance in obesity. PID1 inhibits mitochondrial function and directly binds to the Low Density lipoprotein receptor-related Protein 1, LRP1, although the function of this interaction remains unknown. PID1 mRNA level is also altered in brains of Alzheimer’s patients compared to healthy brains, although here too, its function is not yet known.

Ongoing work in our lab suggests that PID1 plays a central role in a number of important biological processes. Our laboratory studies are now focused on understanding the function and molecular mechanism of PID1 in cancer using in vitro and in vivo approaches. These studies will also help understand the function of PID1 in other processes in health and disease and will guide development of improved therapies

• The Role of GABA Transaminase ABAT in Pediatric Brain Tumor Medulloblastoma Development and Spread
  NIH · R01NS133038 · Jun 1, 2023 – Feb 28, 2028 · Role: Co-Principal Investigator
• USC/CHLA Summer Oncology Research Fellowship (SORF) Program for Medical Students
  NIH · R25CA225513 · Aug 6, 2019 – Apr 30, 2030 · Role: Principal Investigator
• Stabilizing PID1 to improve medulloblastoma response to cisplatin
  NIH · R21NS109751 · Sep 1, 2018 – Aug 31, 2021 · Role: Principal Investigator
• Molecular mechanism of PID1, a novel tumor inhibitor, in glioblastomas
  NIH · R21NS094990 · Sep 1, 2015 – Aug 31, 2018 · Role: Principal Investigator
• Therapy for leptomeningeal medulloblastoma by a novel implantable pump
  NIH · R21NS088965 · May 1, 2014 – Apr 30, 2017 · Role: Principal Investigator
• Tumor-Inhibitory Effects of P1D1 in Gliomas
  NIH · R21NS077007 · Sep 15, 2011 – Aug 31, 2013 · Role: Principal Investigator
• Ceramide in angiogenic integrin signaling
  NIH · R21CA112177 · May 1, 2005 – Apr 30, 2007 · Role: Principal Investigator
• Brain tumor angiogenesis: Integrin ceramide signaling
  NIH · R01CA098568 · Aug 1, 2004 – May 31, 2010 · Role: Principal Investigator

• Biegel, Jaclyn
• Margol, Ashley
• Judkins, Alexander
• Lenz, Heinz-Josef
• Cotter, Jennifer
• Asgharzadeh, Shahab