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 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

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

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 Malnati Brain Tumor Institute of the Lurie Cancer Center. The NSTB provides all Lurie Cancer Center researchers with patient-derived biospecimens and neuropathological support.

For more information, please visit the Horbinski Laboratory website.

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

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 the Sumagin laboratory site.

Contact information

Ronen Sumagin, PhD
Assistant Professor in 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 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 differing approaches provide complementary pathways for identifying novel immunometabolic regulators, which can be used to improve vaccination and immunotherapy strategies by utilizing metabolism as a novel modulator of immunity.

Publications

For additional information, view the faculty profile of Samuel E Weinberg.

Contact

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

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.

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 the 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 treatment for human skin diseases.​

View all of Dr. Yi's publications via PubMed.

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

Contact Us

Email Dr. Yi