Sheena Kerr

The Kerr Lab develops complex fully human microphysiological systems (MPS), which are engineered organ and tissue-mimetic platforms, to model disease across a wide range of pathologies. We integrate functional data from these models with molecular analysis (RNA sequencing, single cell analysis, spatial transcriptomics, protein secretion) and patient clinical data to investigate mechanisms of disease progression, treatment response and resistance. Our projects are focused on several broad areas: 1) cancer and the tumor microenvironment, including patient-specific tumor models of treatment response and resistance, tumor cell phenotypes across metastatic sites and cellular immunotherapies; 2) human immune responses to parasite infection, and 3) modeling inflammatory disease, including endothelial cell biology in sepsis and how aspiration drives inflammation in pneumonia. The lab is highly collaborative and graduate trainees can gain experience spanning MPS design and fabrication, working with primary human cells, and computational analysis of sequencing, imaging and clinical data.

Tumor microenvironment. The tumor microenvironment (TME) refers to the milieu of cells that surround tumor cells including fibroblasts, immune cells, blood and lymphatic vasculature. The multicellular crosstalk between TME cells and tumor cells can drive tumor proliferation and invasion/metastasis, resistance to treatment and modulation of tumor cell phenotypes. Our MPS aim to recapitulate this TME crosstalk allowing us to investigate the molecular mechanisms underlying this tumor biology. We are currently investigating how lineage plasticity in prostate cancer is modulated by different metastatic microenvironments (lymph node, liver, bone). Other projects in prostate cancer are focused on the TME drivers of migration and invasion and responses to cellular immunotherapies.

Patient-specific models of treatment response and resistance. In advanced head and neck cancer, responses to treatment are on the order of ~50%. Therefore, being able to identify patients who will or will not respond to treatment is critical to improve treatment outcomes. We can isolate multiple cell types from a single piece of tumor tissue (cancer associated fibroblasts, tumor infiltrating leukocytes, tumor epithelial) and build MPS that represent each patient’s TME. These models are treated with standard of care therapies and treatment response can be validated against the actual patient outcomes. Ongoing projects are looking at predicting responses to chemotherapy, radiation and immunotherapies.

Human immune responses to parasitic infection. Toxoplasma gondii (T. gondii) infects approximately a third of the world population and has been well studied in mouse models. However, significant differences between mouse and human immune systems mean that we have little knowledge about the human immune response to acute T. gondii infection. We have an MPS that contains an intestinal epithelial lumen and endothelial lumen that mimics the gut microenvironment. We are using these MPS to investigate early innate immune responses to T. gondii by neutrophils and monocytes.

Investigating disease environments in lung MPS with patient clinical samples. Exposure of healthy MPS to patient clinical samples (e.g., saliva or plasma) results in the MPS exhibiting disease features. We have ongoing projects investigating endothelial cell biology in sepsis in lung MPS incubated with sepsis plasma where we are investigating patient endotypes, treatment response and biomarkers. We have also developed a lung MPS containing both epithelial and endothelial cells; when incubated with patient saliva samples, it allows investigation into inflammatory responses associated with pneumonia.

Publications: https://pubmed.ncbi.nlm.nih.gov/?term=Kerr%20Sheena%20%5BAuthor%5D&sort=date