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The Halbrook Lab at UCI

Pancreatic cancer is a devastating disease with no effective clinical treatments.  Despite a relatively low incidence rate, it is projected to become the 2nd leading cause of cancer-related death in the United States.  The inability to successfully treat patients is in large part due to the complex tumor microenvironment in pancreatic cancer, which limits the delivery of chemotherapy and actively suppresses the immune response, neutralizing immunotherapy approaches. We have identified metabolic mechanisms driving many of these barriers to treatment. 

Our work has defined the exchange of alanine from cancer-associated fibroblasts (CAFs) (i) Sousa et al., Nature 2016, tumor-associated macrophages (TAMs) and cancer cells (ii) Halbrook et al., Cell Metabolism 2019, metabolic support of cancer cells by extracellular matrix (ECM) deposited by CAFs and cancer cells (iii) Kim*, Halbrook*, Kerk* et al., eLife 2021, metabolic programming of TAMs by cancer cells (iv) Boyer et al., eLife 2022, and asparagine exchange between heterogeneous cancer cell populations (v) Halbrook et al., Nature Cancer 2022

In addition, pancreatic cancer is aggressively metastatic, most often widely disseminated by the time of diagnosis.  In the minority of cases where localized disease is found sufficiently early, surgical resection is the most effective treatment option; however the vast majority of these patients succumb to recurrence of the disease. As a result, nearly all patients die with metastatic or recurrent disease

Each of these barriers to patient survival is a complex biological problem. Research in the Halbrook Lab is centered on identifying critical mechanisms shaping the formation and maintenance of the primary and metastatic tumor microenvironment and developing tools to disrupt these interactions to enable effective therapy.  In addition, we are interested in understanding the links between tissue regeneration and inflammation underscoring chronic pancreatic disease and cancer.

The various approaches to these projects should be of interest to students and postdocs looking to work on cancer biology, immunology, metabolism, and physiology.  Trainees in the Halbrook lab will have the opportunity to utilize a combination of in vitro models, co-culture models, mouse models, mass cytometry, single-cell sequencing, metabolomics, and many other cutting-edge research tools in order to tackle these challenges.

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