Pediatrics

My laboratory investigates cellular programs that regulate early hematopoietic cell development. Specifically, we are interested in stem cell self-renewal and B cell differentiation in normal development and malignant transformation. We are particularly interested in how signals activated by double-strand DNA breaks (DSBs) integrate with developmental programs to promote normal differentiation and prevent leukemogenesis.

Research keywords: B cell development; Hematopoietic stem cells; DNA damage

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In the Brossier lab, we are interested in identifying which factors increase the rate of tumorigenesis following oncogenic mutation and the molecular basis underlying this effect, with an eye towards using this information for patient risk assessment and to identify new targets for therapeutic intervention. Projects in the lab revolve around two major themes: (1) how neurodevelopmental factors (cell type, age) affect response to oncogenic mutation, and (2) how environmental factors (including maternal diet) modulate the effects of mutation on the cell of origin and tumor penetrance.

Research keywords: maternal obesity; Neurofibromatosis Type 1; pediatric glioma

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I'm a neuroscientist who works on profoundly neurodegenerative inherited diseases that mostly affect children and young adults. These are lysosomal storage disorders, due to failed lysosomal function. My lab works to understand these diseases better. which brain regions and cell types are affected. We then use this information to better target therapies (gene therapy and enzyme replacement) to the places where they can be most effective. This work has taken us from mice to large animal models and from the brain to the bowel.

Research keywords: neurodegeneration; gene therapy; genetics

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The lab focuses on interactions of pathogenic Gram-negative bacteria with their hosts, using urinary tract infection (UTI) as our primary model. We also investigate modulation of host immune responses by uropathogenic bacteria, and the influence of sex on UTI pathogenesis. For example, we have used new mouse models of UTI to identify the first kidney epithelial receptor for type 1 pili of uropathogenic E. coli (UPEC), and to define how androgen receptor signaling drives increased severity of UTI. These molecular and cellular mechanisms are now being investigated with flow cytometry, snRNAseq, CRISPR and other techniques.

Research keywords: Bacterial pathogenesis; Immunology; Urinary tract infections

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The Janowski lab focuses on the characterization of novel viruses in order to understand the mechanisms by which they cause disease in humans. We are currently studying the role of astrovirus VA1 in causing encephalitis and other diseases in humans. We are utilizing a brain organoid model, murine model, and a reverse genetics system to comprehensively dissect the mechanisms of astrovirus infection.

Research keywords: Virology; Viral pathogenesis; Neuroinflammation

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Work in our lab focuses on immune regulation of graft-versus-host disease (GVHD), a debilitating and potentially fatal complication of hematopoietic stem cell transplantation (HSCT). HSCT can cure high-risk malignancies and other blood and bone marrow diseases, yet success is limited by this devastating complication.
We aim to elucidate the biological mechanisms underlying immune tolerance in HSCT and develop approaches to enhance regulatory immune cells for GVHD prevention and treatment. Our goal is to develop a cellular therapy for GVHD with a bench-to-bedside approach, engineering viable advances for prevention and cure, and making HSCT a safer way to cure hematologic diseases.

Research keywords: T cells; cellular therapy; immune regulation

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Cytokine Storm Syndrome (CSS) is a condition of severe, potentially fatal, inflammation. We use a combination of hypothesis-driven and discovery-based approaches, in vitro and in vivo, to determine host factors that regulate CSS from sterile and infectious causes. We focus on the role of autophagy, cell death, and immunometabolism in macrophages and interacting cells. We leverage mouse models and mouse genetics to define the physiological role of these factors and determine their mechanism of action.

Research keywords: autophagy; macrophages; cytokine storm syndrome

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Our lab studies Klebsiella pneumoniae infections and host response with the goal of informing vaccine development. We use a variety of murine models and immunologic assays to study the interplay between bacteria and host. We collaborate with both academia and industry to test cutting-edge vaccine technology and potential therapeutics. We are seeking postdoctoral candidates with experience in bacteriology, immunology, or bioinformatics.

Research keywords: Klebsiella virulence; Vaccines; Immune Response

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The Schuettpelz lab studies how inflammation regulates hematopoietic stem cells (HSCs) and contributes to the development of hematopoietic malignancies. Inflammatory signals are important for the normal development of the immune system and the response to acute infection or injury, however sustained inflammatory signaling can impair HSC function. Furthermore, inflammatory signals can promote the clonal expansion of mutant HSCs and the development of hematopoietic malignancies. Understanding how both normal and mutant HSCs respond to inflammation is important for identifying strategies to optimize HSCs function and prevent blood cancers.

Research keywords: stem cells; inflammation; cancer

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