Immunohistochemistry of ferritin from livers with (left) and without (right) NCOA4 expression. Ferritin accumulates in livers without NCOA4 as NCOA4 is critical for the turnover of ferritin via selective autophagy.
Naiara Santana-Codina and Sebastian Gableske are co-first authors on a paper from the lab identifying a cell autonomous role of NCOA4 in erythropoiesis. Joe initially discovered NCOA4 as the selective autophagy receptor for ferritin, the cellular iron storage complex, during his post-doctoral work. Prior work in the lab identified that loss of NCOA4 perturbs cellular iron homeostasis. While we initially discovered this process in pancreatic cancer cells, we realized that this process is more generalized to all cells. Therefore, we hypothesized that loss of NCOA4 in an organism (a mouse in this instance) would perturb systemic iron homeostasis and the most iron-dependent process in mammals: normal erythropoiesis (red blood cell production). To address these questions, we developed novel conditional knockout mouse models of NCOA4 and performed targeted deletion of NCOA4 in red blood cells as well as induced acute systemic NCOA4 loss in adult mouse. Our work was the first to show a critical role of NCOA4 in adult animals for maintaining iron homeostasis and a role for NCOA4 in maintaining erythropoiesis. Paper is here: Haematologica and on PubMed Central.
Next, we will look at the effects of NCOA4 loss (and gain) in pancreatic tumors given these tumors highly upregulate autophagy and rely on high levels of iron. Stay tuned for further results!
Lab publishes a paper in Haematologica: NCOA4 Maintains Murine Erythropoiesis Via Cell Autonomous And Non-Autonomous Mechanisms
Joe presents at the NCI GI-Pancreas SPORE Workshop hosted at the University of Nebraska Medical Center
As part of the team representing the GI SPORE at Dana-Farber/Harvard Cancer Center, Joe presents his work on therapeutic resistance to pre-clinical targeted therapy in Pancreatic Cancer models, including published work on glutaminase inhibitors and unpublished work (supported by a Career Enhancement Program Award from the DF/HCC GI SPORE) on pharmacologic oncogenic KRAS inhibitors. Check out the agenda of the meeting here: GI SPORE Workshop Agenda. Fantastic hosts at the UNMC show us their amazing Chihuly Sanctuary, pictures below!
Joe attends and presents at a fantastic meeting on Pancreatic Cancer organized in part by Dr. Brian Wolpin of DFCI. Joe presents on initial work from the lab investigating how to use mass spectrometry-based quantitative proteomics to identify adaptations to oncogenic KRAS inhibition.
The lab welcomes Dr. Miljan Kuljanin to the lab! Miljan just completed his graduate work at Western University in Ontario, Canada. During his graduate work he developed extensive expertise in quantitative proteomics and mass spectrometry instrumentation while working on projects related to biomarker discovery in diabetes and identification of therapeutic targets for beta-cell regeneration in patients with diabetes. Check out one of his recent publications in Cell Reports: Quantitative Proteomics Evaluation of Human Multipotent Stromal Cell for β Cell Regeneration. The Mancias Lab is excited for him to join the lab and spearhead our quantitative proteomics and mass spectrometry efforts. He'll be jointly mentored by the Mancias Lab, the Chowdhury Lab at DFCI and the Gygi Lab at Harvard Medical School.
The Hale Family Pancreatic Cancer Research Center has designed a website to engage the research, medical, and patient communities around their ongoing research and clinical translational finding in pancreatic cancer. Ole Gjoerup led the charge on the website with oversight from Joe Mancias.