Carcinogenesis/Neoplasia

Research Description

Mechanisms Underlying Glioblastoma Progression

We investigate mechanisms of progression to glioblastoma (GBM), the highest-grade astrocytoma, including genetics, hypoxia and angiogenesis. Progression is characterized by tumor necrosis, severe hypoxia and microvascular hyperplasia, a type of angiogenesis. We propose that vaso-occlusion and intravascular thrombosis within a high-grade glioma result in hypoxia, necrosis and hypoxia-induced microvascular hyperplasia in the tumor periphery, leading to outward neoplastic expansion. Since the pro-thrombotic protein tissue factor is upregulated in gliomas, we investigate mechanisms of increased expression and pro-coagulant effects.

In Silico Brain Tumor Research

We initiated an In Silico Center for Brain Tumor Research to investigate the molecular correlates of pathologic, radiologic and clinical features of gliomas using pre-existing databases, including The Cancer Genome Atlas (TCGA) and Rembrandt. Using datasets and image analysis algorithms, we study whether elements of the tumor microenvironment, such as tumor necrosis, angiogenesis, inflammatory infiltrates and thrombosis, may correlate with gene expression subtypes in TCGA gliomas. We have also demonstrated the clinical relevance of TCGA subclasses within lower-grade gliomas using the Rembrandt dataset.

Regulators of Asymmetric Cellular Division in Glioblastoma Stem Cells

We study mechanisms that confer specialized biologic properties to glioma stem cells (GSC) in GBM. The Drosophila brain tumor (brat) gene normally regulates asymmetric cellular division and neural progenitor differentiation in the central nervous system of flies and, when mutated, leads to a massive brain containing only neuroblastic cells with tumor-like properties. We study the human homolog of Drosophila brat, Trim3, for its role in regulating asymmetric cell division and stem-like properties in GSCs. Trim3 may exert its effects through repression of c-Myc.

For more information, visit the faculty profile of Daniel Brat, MD, PhD, or the Brat Lab website.

Publications

See Brat's publications in PubMed.

Contact

Email Daniel Brat, MD, PhD.

Research Interests

Our research goal is to identify the therapeutic molecular targets for the treatment of autoimmune diseases, particularly rheumatoid arthritis (RA) and Type 1 diabetes (T1D).

In our laboratory, we use genetic, proteomic, molecular biology and immunological approaches to dissect the molecular networks underlying the regulation of immune response and autoimmunity. Several specific genes that are critical for immune regulation and autoimmune diseases have been identified in our laboratory. Small molecules that modulate the functions of these newly identified genes can potentially be used to treat T1D and RA.

Current Ongoing Research Projects

1. Sirt1, a type-iii histone deacetylase, is required for immune tolerance.
2. The ubiquitin E3 ligase Synoviolin is a therapeutic target for RA.
3. The tyrosine kinase c-Abl in T-cell differentiation and allergic lung inflammation.
4. The roles of RoxP3 in regulatory T cells.
5. Ubiquitination in aging and autoimmunity.
6. Novel microRNAs in immune tolerance and autoimmunity.

For more information, visit the faculty profile of Deyu Fang, PhD, or the Fang Lab website.

Publications

See Fang's publications in PubMed.

Contact

Email Deyu Fang, PhD.

Research Interests

The Ji Lab is interested in how cytoskeletal signaling, motor proteins and adhesion systems integrate with chemical signaling pathways to regulate cell behavior, tissue differentiation and disease. Our lab studies small G proteins and downstream actin regulatory effectors that participate in enucleation during red cell development.

At the nuclear level, the Ji lab studies genes involved in erythroid lineage commitment, chromatin condensation and enucleation to understand how congenital red cell disorders and leukemia develop. 

For more information, visit the faculty profile of Peng Ji, MD, PhD.

Publications

See Ji's publications in PubMed.

Contact

Email Peng Ji, MD, PhD.

Research Description

Immune cells are critical for host defense; however, immune cell infiltration of mucosal surfaces during inflammation significantly alters tissue homeostasis. This includes restructuring of the extracellular matrix and alterations in cell-to-cell adhesions. Particularly, immune cell-mediated disruption of junctional adhesion complexes, which otherwise regulate epithelial cell polarity, migration, proliferation and differentiation, can facilitate both tumorigenesis and cancer metastasis. Our research thus focuses on understanding the mechanisms governing leukocyte-induced tissue injury and disruption of epithelial integrity as potential risk factors for tumor formation, growth and tissue dissemination.

For publication information, see PubMed, and for more information, see the faculty profile of Ronen Sumagin, PhD, or visit the Sumagin Lab website.

Contact

Ronen Sumagin, PhD
Associate Professor of Pathology (Experimental Pathology)
312-503-8144
Email: ronen.sumagin@northwestern.edu

Research Interests

The main goal of our laboratory is to unravel how metabolic processes in rare immune cell populations regulate the generation and function of adaptive immune responses in clinically relevant contexts. Specifically, the laboratory utilizes a combination of unbiased CRISPR screening, an innovative metabolomics method, high-parameter flow cytometry, single-cell transcriptomics and rigorous animal models to identify novel metabolic regulators of immune cell function in a wide range of conditions, including cancer, infection and autoimmunity. These approaches provide complementary pathways for identifying novel immunometabolic regulators that can improve vaccination and immunotherapy strategies by using metabolism as a modulator of immunity.

Publications

For additional information, visit the faculty profile of Samuel Weinberg, MD, PhD.

Contact

Contact the Weinberg Lab at samuel-weinberg@northwestern.edu.

Research Description

Mammalian skin and its appendages function as the outermost barrier of the body to protect inner organs from environmental hazards and keep essential fluid within. Our research program studies mechanisms that govern cell fate specification, stem cell maintenance and aging, as well as initiation and progression of cancer. We use single-cell genomics and computational tools, live animal imaging and genetically engineered mouse models to study gene expression regulation mediated by transcription factors, epigenetic regulators and post-transcriptional mechanisms mediated by miRNAs and RNA-binding proteins at single-cell resolution in mammalian skin.

Our research aims to address several fundamental questions in stem cell biology: how the developmental potential of embryonic progenitors and adult tissue stem cells is transmitted or restricted in their progenies at the molecular level when they go through critical transitions such as cell fate specification, self-renewal of stem cells as well as stress response, and how these regulatory mechanisms go awry in aging and diseases. Answers to these questions will help to manipulate skin stem cells for regenerative medicine and discover new treatments for human skin diseases.

See Yi's publications via PubMed.

For more information, visit the faculty profile of Rui Yi, PhD, or visit the Yi Lab website.

Contact Us

Email Rui Yi, PhD

Our lab studies the regulators of inflammatory signaling in hematopoietic cells — both in normal and malignant conditions. By leveraging advanced technologies, mouse models and patient samples, we aim to discover new therapeutic strategies to slow the progression of hematological cancers.

For more information, visit the faculty profile of Johanna Melo-Cardenas, PhD, or the Melo-Cardenas Lab website.