Dr. Eric Rahrmann joined the Hormel Institute as an Assistant Professor focusing his effort on understanding the fundamentals of why cancer spreads. Eric completed his graduate training in the laboratory of Dr. David Largaespada at the University of Minnesota, where he utilized in vivo forward genetic screens in mouse models to identify novel driver genes and potential therapeutic targets of diffuse large B cell lymphoma and peripheral nerve tumors (neurofibromas and malignant peripheral nerve sheath tumors).
He has authored papers in top-tier journals, including a first author in Nature Genetics. In 2013, Eric began his post-doctoral training with Professor Gilbertson while at St. Jude Children’s Research Hospital in Memphis, Tennessee. His studies focused on understanding the importance of restingmembrane potential on stem cell fate, and he was awarded the Neurobiology and Brain Tumour Program Garwood Named Fellowship for his research.
In 2015, Eric was awarded a Marie Sklodowská-Curie individual Fellowship and promoted to Senior Research Associate to continue his training at the University of Cambridge with Prof Gilbertson at Cancer Research UK – Cambridge Institute. His work focused on the role of ion channel regulated membrane potential in cell dissemination in malignant and non-malignant tissues whereby he has divorced the process of metastasis from upstream oncogenic transformation.
Through a series of genetically engineered mouse models of gastric, intestinal and pancreatic adenocarcinomas, he demonstrated that loss of function of NALCN (genetic deletion or pharmacological blockade with gadolinium) increased circulating tumor cells and metastases without impacting primary tumor characteristics. This work was published in Nature Genetics and led to three patents which covers the topics of metastasis early detection, anti-metastatic therapeutics and cellular therapies for regenerative medicine.
Primary Research Areas, Research Specialties
- Metastasis
- Circulating tumor cells
- Molecular biology
- Developmental biology
- Stem cells
- Ion channels
- Genetic mouse models
- Organoids
Research Interests
A Paradigm Shift in Cancer Metastasis: NALCN’s Role in Epithelial Cell Trafficking
There are 611,720 cancer-related deaths projected to occur in the US in 2024. The majority of cancer-related deaths are a result of metastasis, a process where cancer cells spread from the primary tumor to other organs in the body.
Despite a wealth of studies over decades, this process remains poorly understood and resistant to treatment. Metastasis has been assumed to be an abnormal process mediated by primary cancers. However, our groundbreaking work is the first to divorce metastasis from upstream tumorigenesis and link it to a novel physiologic process, which is central to the maintenance of normal tissues, uncovering a completely new paradigm for metastasis.
Specifically, Dr. Rahrmann identified the Sodium Leak Channel Non-Selective Protein (NALCN) as a key regulator of epithelial cell trafficking, both normal and malignant tissues, unmasking this cascade as a cancer-independent phenomenon and a novel therapeutic target (Rahrmann et al. 2022).
These findings will allow refinement of the current model of metastasis and have unmasked a potential novel target for anti-metastatic therapies. Yet, there are several outstanding questions revolving around both the understanding of the biochemical and cellular mechanisms involved in NALCN-regulated cell dissemination and if our findings extend more broadly to other cancer types.
Our initial findings focused on mouse models of gastric, intestinal, and pancreatic adenocarcinomas and were based on evidence of significant enrichment of NALCN mutations in human gastrointestinal cancers.
Preliminary analysis of human cancers that commonly metastasize, but lack enrichment of NALCN nonsynonymous mutations, has identified that reduced NALCN copy number (heterozygous and homozygous deletion, GISTIC scores) is associated with more aggressive breast adenocarcinomas and metastasis to intraperitoneal organs.
The central hypothesis is that ion channels regulate normal mammary gland and breast adenocarcinoma plasticity and cell dissemination by altering membrane potential, which can be leveraged for the development of effective therapies. Understanding this process of cell plasticity and dissemination not only creates a platform for identifying new anti-metastatic drugs in cancer models, but could also be leveraged in normality for tissue repair and regenerative medicine.
Professional Memberships
- AACR
- Metastasis Research Society
- EACR