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Northwestern University Feinberg School of Medicine
Department of Pathology
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Carcinogenesis/Neoplasia

The study of cancer at the basic and translational level focuses on cellular and molecular mechanisms of neoplastic development and progression, as well as the tumor microenvironment and the development of novel targeted therapies.

Learn more about our work below.

 Daniel Brat Lab

Mechanisms Underlying Glioblastoma Progression and Regulators of Asymmetric Cellular Division in Glioblastoma Stem Cells

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 results in hypoxia, necrosis and hypoxia-induced microvascular hyperplasia in the tumor periphery, leading to neoplastic expansion outward. 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 as TCGA and Rembrandt. Using datasets and image analysis algorithms, we study whether elements of the tumor micro-environment, such as tumor necrosis, angiogenesis, inflammatory infiltrates and thrombosis, may correlate with gene expression subtypes in TCGA gliomas. We also have demonstrated the clinical relevance of TCGA subclasses within the 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 CNS 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 elicit its effects is through repression of c-Myc.

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

Publications

See Dr. Brat's publications in PubMed.

Contact

Email Dr. Brat

 Deyu Fang Lab

Studying molecular networks in the regulation of immune response and autoimmunity

Research Interests

Our research goal is to identify the therapeutic molecular targets for the treatment of autoimmune diseases particularly of 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 type 1 diabetes and rheumatoid arthritis.

The current ongoing research projects, in my laboratory are:

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 Dr. Deyu Fang's faculty profile or laboratory site.

Publications

See Dr. Fang's publications in PubMed.

Contact

Dr. Fang

 Craig Horbinski Laboratory

Studying the effects of altered glioma metabolism in the microenvironment.

My translational work focuses on the effects of altered glioma metabolism in the microenvironment. Mutations in isocitrate dehydrogenase 1 or 2 (mutant IDH1/2) are present in a large proportion of gliomas, and are known to alter tumor metabolism and DNA methylation. Additionally, I serve as the Director of the Nervous System Tumor Bank (NSTB) for the Northwestern Brain Tumor Institute. The NSTB provides all NBTI researchers with patient-derived biospecimens and neuropathological support.

For more information, please visit the Horbinski Laboratory website.

 Peng Ji Lab

Role of MDia1 in the pathogenesis of del(5q) myelodysplastic syndromes

Research Interests

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

At the level of the nucleus, the Ji laboratory studies genes involved in erythroid lineage commitment, chromatin condensation and enucleation towards understanding how congenital red cell disorders and leukemia develop. 

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

Publications

See Dr. Ji's publications in PubMed.

Contact

Dr. Ji

 Ronen Sumagin Lab

Contributions of immune cell-mediated inflammation to development and progression of colorectal cancers

Research Description

Immune cells are critical for host defense, however immune cell infiltration of mucosal surfaces under the conditions of inflammation leads to significant alteration of the 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 Dr. Sumagin's faculty profile page or laboratory site.

Contact information

Ronen Sumagin, PhD
Assistant Professor in Pathology
312-503-8144
Email:  ronen.sumagin@northwestern.edu

 Guang-Yu Yang Lab

Principal Investigator: Guang-Yu Yang, MD, PhD
Research Interest: Interaction of genetic mutations and inflammation in the pathogenesis of pancreatic and colon cancer

The Yang lab is interested in cancers of the GI tract including liver, pancreas and colorectal. The long-term objective of their studies is define molecular mechanisms and chemoprevention strategies for chronic inflammation-driven carcinogenesis. They study how inflammation and nitro-oxidative stress contribute to DNA damage, cell proliferation and inflammation-driven carcinogenesis.

A major goal of Yang group is to develop chemoprevention strategies for cancers of the pancreas, liver and gut. They are particularly interested in dietary nutrients, antioxidants, green tea and inositol compounds to target these cancers.

Contact Us

Fang, Deyu

Deyu Fang

Professor of Pathology (Experimental Pathology)

Sumagin, Ronen

Ronen Sumagin

Assistant Professor of Pathology (Experimental Pathology)

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