The mission of the Monteith laboratory is to explore the delicate balance existing between metabolic and inflammatory processes, and how perturbations in this equilibrium promote disease. We leverage our expertise across multiple diseases with the hopes of developing impactful immunological discoveries and translating our findings to improve human health.

Innate immunity during Staphylococcus aureus infection

S. aureus asymptomatically colonizes 20-30% of the population, but once the barrier to the host is breached, S. aureus has evolved an arsenal of virulence strategies to subvert the immune response and infect nearly every tissue in the body. As such, S. aureus is the leading cause of soft tissue infections, bacterial endocarditis, and second most frequent agent of hospital-associated pneumonia and bloodstream infections. S. aureus infections frequently require antibiotics to resolve; however, as viable antibiotic treatments for S. aureus narrow, understanding the interactions at the host-pathogen interface is critical to developing future therapeutics. We seek to understand how neutrophils ‘sense’ disruptions elicited by bacterial pathogens and shape their inflammatory processes to suit the metabolic constants of the environment. We have made significant contributions to mitochondrial regulation of neutrophil extracellular trap (NET) formation and will continue to probe how NETs act as a conduit to cooperatively combat bacterial pathogens in conjunction with other immune cells.

Metabolic dysregulation in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a national prevalence of 322,000 individuals (~1:1,000) with a significantly higher incidence rate amongst women of color. The underlying cause of SLE is unknown, but multiple genetic and environmental components contribute to the inflammation associated with disease. An improved understanding of these early molecular events in SLE is necessary to developing novel strategies that disrupt chronic inflammation. We seek to understand how altered mitochondrial homeostasis in macrophages and neutrophils drive a feedforward loop in tissue-damaging inflammation and render SLE patients more susceptible to bacterial infection.

Metabolic controls of hematopoiesis and cancer

Myelodysplastic syndromes (MDS) are a group of clonal malignant diseases of hematopoietic stem and progenitor cells (HSPCs) characterized by ineffective hematopoiesis, which may lead to multilineage cytopenias and bone marrow failure. In addition, MDS leads to an increased risk of transformation to acute myeloid leukemia (AML), which is a molecularly heterogenous bone marrow malignancy resulting from differentiation arrest of HSPCs, and an uncontrolled proliferation of these early cells. By using different sources of nutrients, malignant cells gain a metabolic plasticity which complicates treatment, while allowing them to outcompete normal hematopoietic cells. We seek to understand how shifts in metabolic intermediates in the bone marrow disrupt hematopoiesis and sustain pathogenic epigenetic modifications in MDS and AML.

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