Research

Mission Statement

The Rutkowski lab is focused on understanding how commensal microorganisms tip the balance to impact anti-tumor immune function, tumor growth and metastasis, and response to cancer therapy. Our projects elucidat how commensal microorganisms affect systemic immunity and tissue homeostasis with a focus on cancer. We have developed a model to study how the gut microbiome worsens metastasis of estrogen- and progesterone-receptor positive (HR+) Her2neg breast cancer to the lungs. Related projects seek to understand how modulating host metabolism by perturbing gut microbiota impacts cancer outcomes. Similarly, we study how the immune system interfaces with the host microbiome via antagonism of Toll-Like Receptors (TLRs) and how these interactions affect tumor immune surveillance and response to immune therapies. Finally, we are developing novel therapeutic strategies to counteract the microbiota’s negative effects on the immune system during cancer progression and in other diseases.

Research Projects

How do gut microbiome-driven changes in host metabolic function impact cancer outcomes?
Changes in the gut microbiome affect host metabolism due to gut leakage, inflammation, and systemic shifts in commensal-derived metabolites. Multiple cancers are impacted by these changes in insulin and glucose dynamics resulting in metastasis, poor outcomes, and an immune deserted tumor environment. Generally, changes in insulin glucose dynamics are associated with obesity. However, we find that disruption of the gut microbiota alone is sufficient to trigger insulin resistance in female mice. Here, we aim to disentangle the impact that the microbiome and microbial-derived metabolites, obesity, and insulin/glucose signaling have on systemic tissue immune homeostasis, tumor progression and metastasis.

How does the commensal microbiome influence tumor metastasis?
Seminal studies from our lab demonstrated that commensal dysbiosis, an inflammatory microbiome with low diversity, results in long-term cellular and molecular changes to the mammary gland and other distal tissues, increasing the ability of primary breast tumors to disseminate and seed metastatic sites. We are defining how commensal dysbiosis enhances tumor metastasis, with a focus on defining critical cellular or molecular features of the mammary tissue and distal organs affected by dysbiosis.

Does commensal dysbiosis influence tumor cell signaling or response to therapy?
Cancer does not occur in a vacuum. As the tissue stroma, vasculature, and immune cells respond to dysbiosis, tumor cells change as well. We study how tumor cells respond to specific perturbations in the gut microbiome, and whether these changes associate with resistance to targeted immune therapies.

Does microbial dysbiosis or gut leakage impact systemic immune function?
We have demonstrated that interactions between immune cells and the commensal microbiome are a mechanism of failure for immune therapy in ovarian cancer. Many extraintestinal cancers cause gut leakage, indicating that this pathway may be involved in immune therapy failures across a spectrum of cancers. We study how chronic engagement with commensal microbiota affects immune cells systemically and within the tumor microenvironment. We aim to develop therapeutics that mitigate the deleterious consequences of gut leakage and restore the body’s ability to fight tumors during immune therapy.