Mancias Lab - Pancreatic Cancer Research - NEWS

Paper published in Cancer Discovery today

9/1/2022

Our study was published today in Cancer Discovery! The study is entitled "NCOA4-Mediated Ferritinophagy Is a Pancreatic Cancer Dependency via Maintenance of Iron Bioavailability for Iron–Sulfur Cluster Proteins". Briefly, the cell autonomous metabolic role of autophagy in pancreatic adenocarcinoma (PDAC) has been studied in detail; however, it remains unclear what are the substrates that autophagy provides to support tumors. Using pre-clinical models of PDAC, we now identify that NCOA4-mediated selective autophagy of ferritin, the cellular iron storage complex, is upregulated in PDAC to support iron metabolism for iron-sulfur cluster protein function. Targeting NCOA4 delays tumor progression and prolongs survival. These results align with data from patient cohorts where a low ferritinophagy expression signature correlates with improved survival in PDAC patients. This study defines NCOA4-mediated ferritinophagy as a therapeutic target in PDAC.

In addition to our study, our collaborators at UCSF (Perera Lab) published a study in the same edition identifying that NCOA4-mediated ferritinophagy is upregulated in response to MAPK pathway inhibition suggesting a useful combination therapy for pancreatic cancer.

Finally - both of our studies were featured on the cover of the journal (image above - credit to Cancer Discovery) and reviewed in a great preview authored by the Amaravadi Lab.

Welcome to the lab, Dr. Myungsun Shin!

8/31/2022

We are excited to welcome Shin to the lab as a joint Postdoctoral Fellow with the Gygi Lab (Harvard Medical School). Shin joins the lab after a successful PhD in the lab of Professor Ku-Lung Hsu at the University of Virginia, Department of Chemistry. At UVA Shin developed expertise in Mass-Spectrometry based Proteomics and Lipidomics analysis and investigated the functional role of lipases in immune cells. His work led to multiple first author publications such as Shin et al. DAGL-Bega Functions as a PUFA-Specific Diacylglycerol Lipase in Macrophages. Cell Chem Bio 2020). We are excited for Shin to join the lab and work on applying quantitative mass spectrometry-related proteomics to many different pancreatic biology questions and developing new methodologies for drug discovery.

Welcome to the lab, Dr. Thuy Nguyen!

8/1/2022

Welcome to the lab, Dr. Thuy Nguyen! Thuy joins the lab after a successful graduate school experience in the lab of Professor Tae-Il Jeon at the Chonnam National University in South Korea. There, Thuy discovered a novel mechanism of sterol regulator element binding protein - 1c (SREBP-1c) in autophagy flux, contributing to hepatic steatosis in high-fat diet mice. This work resulted in a first author paper entitled: "SREBP-1c impairs ULK1 sulfhydration-mediated autophagic flux to promote hepatic steatosis in high fat diet fed mice". (Nguyen et al. Molecular Cell 2021). We are excited to welcome Thuy to the lab where she will work on further understanding the role of selective autophagy in pancreatic cancer.

Welcome to the lab, Matthew Dorman!

7/13/2022

Welcome (back) to the lab, Matt! Matt was previously in the lab as a Boston University Master's student and successfully completed a thesis in the lab. He now joins the lab as a Research Technician who will help with multiple projects related to pancreatic cancer biology while preparing for medical school applications.

Welcome to the Lab, Claudia Campos!

7/11/2022

We are excited for Claudia to join the lab. Claudia just graduated from Tennessee Wesleyan University with Honors while majoring in Biology. During her undergraduate time she worked in multiple labs, including at the Oak Ridge National Laboratory. In the lab Claudia will be working on projects related to pancreatic cancer radioresistance and understanding resistance to newly developed oncogenic KRAS inhibitors.

We are hiring a postdoctoral fellow - come join the lab!

7/7/2022

We are hiring a fully funded postdoctoral fellow! Check out the posting and apply via this link:
https://careers.dana-farber.org/job/postdoctoral-research-fellow-mancias-lab-fellowships-boston-ma-30219/
Contact Joe Mancias with any questions about the position.

Going away party for Naiara!

7/1/2022

We celebrated Dr. Naiara Santana-Codina's time in the lab at TimeOut Market! Naiara was one of the first members of the lab and has had an amazingly productive time in the lab with three first author research articles (in Cancer Discovery, Nature, Haematologica, Cell Reports) and multiple first author reviews (including in Annual Reviews of Cancer Biology). Naiara also won multiple awards including an individual grant to fund a portion of her research in the lab! We are so excited for Naiara as she takes her next big step as a new Principal Investigator! Good luck Naiara!

New paper from the lab published in Cancer Discovery!

6/30/2022

Our latest publication is now online at Cancer Discovery! Here, we demonstrate that "NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins." To study the role of NCOA4 in PDAC, we used orthogonal approaches including bioinformatics of large-scale loss-of- function genetic screens, autochthonous tumor models, cell lines, and human tumor genetics. Naiara Santana-Codina led the work with significant contributions from many others in the lab as well as collaborations from the Nowak Lab and the Aguirre Lab at DFCI , and Yatrik Shah's lab at University of Michigan. Check out the study at this link:
https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-22-0043/704854/NCOA4-mediated-ferritinophagy-is-a-pancreatic

We are hiring research technicians!

2/4/2022

The Mancias Lab is hiring research technicians! Join our team to work on projects related to pancreatic cancer, autophagy, and iron. Apply via the links below.

The individuals will be an important member of our research team and will be involved in assisting research projects utilizing several techniques that are fundamental to the workflow of the Mancias Lab. In addition to the bench-based research, responsibilities will also include some aspects of laboratory management and organization. Training is available in all aspects of experimental research.

This is a great position for an individual interested in attending a biomedical graduate school program or medical school (or MD/PhD program). Mentoring for graduate/medical school applications is available through the principal investigator as well as clinical shadowing opportunities. Prior research technicians in this position have gone on to medical school and graduate school and have been first author and/or co-author on peer-reviewed publications by the time they left the laboratory.

https://social.icims.com/viewjob/pe164321406814123f60

For a candidate with some experience handling animal models (mouse models):
https://social.icims.com/viewjob/pe164321389274431922

We are co-hiring (with the Gygi Lab) a postdoctoral fellow!

11/23/2021

Our lab and the lab of Steven Gygi, Ph.D. at Harvard Medical School are co-hiring a fully funded postdoctoral fellow to begin as early as January 2022. For additional details, please see the post to the left or click on this link:

https://careers-dfci.icims.com/jobs/26451/research-fellow---mancias-lab/job?mode=view&mobile=false&width=791&height=500&bga=true&needsRedirect=false&jan1offset=-300&jun1offset=-240

Please apply via the link or by e-mail: [email protected] with a Curriculum Vitae and a cover letter.

We look forward to hearing from you!