Brooke R. Druliner, Ph.D.

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SUMMARY

The research interests of Brooke R. Druliner, Ph.D., are the molecular mechanisms of normal and dysfunctional epigenetic memory programs in the context of chromatin that regulate intestinal stem cell function. Dr. Druliner's laboratory utilizes a combination of chromatin and stem cell biology approaches and organoid models of stem cells — in combination with cutting-edge technology such as genome engineering and single-cell multiomics — to study intestinal stem cell regulation in multiple disease contexts.

A key question in the biology of stem cells is how they maintain stemness, or their ability to balance self-renewal and a new pathway of terminal differentiation. As there are no differences in the DNA sequence between the stem and daughter cells, the maintenance of stemness occurs by establishing an epigenetic memory program. Epigenetic memory involves lasting modification to chromatin at multiple scales, which impacts transcriptional programs required for normal stem cell functions.

Focus areas

• Epigenomic memory mechanisms regulating intestinal stem cells in homeostasis and disease. Dr. Druliner's laboratory focuses on identifying the mechanisms that maintain the epigenetic state across the continuum of epithelial stem cell renewal, expansion and cell-type specification in normal and dysfunctional stem cell regulation. This research aims to answer the overarching question: Does the intestinal stem cell retain a memory of altered chromatin machinery and resultant architectures in disease?
• Organoids and multicellular model systems. Dr. Druliner and her colleagues have generated organoids from Mayo Clinic patients, both normal and diseased tissues including colorectal cancer and inflammatory bowel disease. This includes work to increase the system complexity to recapitulate the multicellular context of an organ and its microenvironment in an in vitro system.
• Applying a genome engineering toolkit to organoid models. The organoid model system allows for genome editing at the stem cell, which then divides and gives rise to other progenitor and differentiated epithelial cell types within the organoid. Dr. Druliner's team and their collaborators apply established and novel gene-editing technology to characterize the epigenetic factors required for stem cell maintenance while also developing a functional toolkit of gene-engineering approaches in organoid systems that will be available for use by the scientific community.

Significance to patient care

Dr. Druliner's laboratory is focused on basic and translational studies to better understand gastrointestinal tract diseases such as colorectal cancer and inflammatory bowel disease. The information gained by understanding the normal and dysfunctional epigenetic memory programs regulating intestinal stem cell function has the potential to be harnessed for predictive or therapeutic strategies in these diseases.

Professional highlights

• Loan Repayment Award, National Institutes of Health Division of Loan Repayment, 2021-present.
• Member, Research Award Panel, American Gastroenterological Association (AGA), 2021-present.
• KL2 Career Development Award, Center for Clinical and Translational Sciences, Mayo Clinic, 2020-present.
• Minnesota Colorectal Cancer Research Fellowship Award, Minnesota Colorectal Cancer Research Foundation, 2019-2020.
• Member, AGA, 2016-present.