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!

With Ole Gjoerup, Joe Mancias helps start the Hale Pancreatic Cancer Center Twitter account to more broadly engage the Pancreatic Cancer scientific community. 

The Mancias Lab is a proud member of the Hale Pancreatic Cancer Center whose objective is to develop more effective pancreatic cancer treatments by uniting laboratory and clinical experts in gene discovery, functional genomics, computational biology, chemical biology, and model system development by:

• Fostering collaboration at Dana-Farber Cancer Institute and across the world-class biomedical community in Boston to accelerate pancreatic cancer research and rapidly translate discoveries into improved patient outcomes
• Fueling a pioneering effort to address challenges in pancreatic cancer prevention, diagnosis, and treatment, and is already transforming our understanding about the biology driving this disease. 

The annual Lab Holiday in recognition of all the hard work ongoing in the lab was such a success we only remembered to take this one great picture of Seb displaying his drink with a shrub in it! Much fun was had at A4cade playing arcade games and some extremely competitive Skee-Ball rounds (ongoing dispute as to who actually scored the most). Finished up the night with a great dinner at Little Donkey!

As part of Pancreatic Cancer Awareness Month, the lab walks together to support Promises for Purple, a non-profit organization for pancreatic cancer awareness founded in 2009 by Claire Muollo, a Dana-Farber Cancer Institute pancreatic cancer patient who unfortunately lost her battle to pancreatic cancer in 2014. Her family and friends continue her legacy with annual Promises for Purple walks. 

Naiara Santana-Codina publishes an invited review in a special issue of Pharmaceuticals on the role of iron metabolism in health and disease. Her review focused on the growing body of evidence from the Mancias Lab and others linking NCOA4, the selective autophagy receptor for ferritin, with important physiologic processes such as erythropoiesis and with pathophysiology including iron deficiency anemia, ferroptosis (an iron-dependent form of cell death), neurodegeneration, and potentially cancer. Check out the open access article here: ​The Role of NCOA4-Mediated Ferritinophagy in Health and Disease.

The annual Mancias Lab BBQ was a ton of fun! So much so that we forgot to take a more than these couple of pictures: evidence of all the food we ate and Mark and Miljan showing off their corn hole skills. Also, a little rain didn't stop the party!