Inflammation/Immunology

Research Overview

The Cui Lab studies T-cell biology, focusing on T-cell differentiation, function and epigenetic regulation in various inflammatory settings, including acute and chronic viral infections, autoimmune disorders and cancer. T-cells are members of the adaptive immune system and are critical for defense against bacteria, viruses and malignant cells. The lab aims to better understand how T-cells respond to different inflammatory stimuli using murine models of acute and chronic viral infection, type 1 diabetes, melanoma and bladder cancer.

Current Research Interests

• T-cell differentiation in chronic infection
• Adoptive cell transfer for cancer
• T-cell memory

For more information, visit the faculty profile of Weiguo Cui, PhD, or the Weiguo Cui Lab website.

Publications

View lab publications on the National Library of Medicine.

Contact

Email Weiguo Cui, 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 Description

Most diseases are due to or involve a significant component of inflammation. The Muller Lab studies the inflammatory response at the cellular and molecular level. We focus on diapedesis, the "point of no return" in inflammation when leukocytes squeeze between tightly apposed endothelial cells to enter the site of inflammation. We have identified and cloned several molecules critical to diapedesis (PECAM (CD31), CD99, and VE-cadherin) and are studying how they regulate the inflammatory response using in vitro and in vivo models. We have recently described the Lateral Border Recycling Compartment, a novel para-junctional organelle that contains PECAM and CD99 and is critical for diapedesis to occur. We are currently investigating how this compartment regulates diapedesis in the hope of finding novel and highly specific targets for anti-inflammatory therapy.

The "holy grail" of therapy is to develop selective anti-inflammatory agents that block pathologic inflammation without interfering with the body’s ability to fight off infections or heal wounds. By understanding how endothelial cells at the site of inflammation regulate leukocyte diapedesis, we are hoping to do just that. We have identified several molecules critical for diapedesis in acute and chronic inflammatory settings that can be genetically deleted or actively blocked to markedly inhibit clinical symptoms (e.g., in a mouse model of multiple sclerosis) and tissue damage (e.g., in a mouse model of myocardial infarction) without impairing the normal growth, development and health of these mice. Our inflammatory models include atherosclerosis, myocardial infarction, ischemia/reperfusion injury, stroke, dermatitis, multiple sclerosis, peritonitis and rheumatoid arthritis. We also use 4D intravital microscopy to observe the inflammatory response in real time in living animals.

• What are the molecular mechanisms and signaling pathways that endothelial cells use to regulate the inflammatory response?
• How can we therapeutically treat inflammatory diseases without compromising the ability of the immune system to respond to new threats?
• Do circulating tumor cells use the same mechanisms as leukocytes to cross blood vessels when they metastasize?

Our Facilities

We have a high-resolution Perkin Elmer ULTRAVIEW Vox System spinning disk laser confocal microscope in the upright configuration on an Olympus BX51WI fixed stage in my laboratory designed for intravital microscopy. We can image the ongoing inflammatory response and drug responses in real time in anesthetized mice with unprecedented temporal and spatial resolution. We presently image inflammation in the cremaster muscle, intestine and brain.

Of interest to History of Science buffs, we have the original Zeiss Ultrafot II microscope used to film the first movies of neutrophils ingesting bacteria. As you might expect from something built by Zeiss in the first half of the 20^th century, the optics are still fantastic and we use it in our daily work.

For more information, visit the faculty profile of William A Muller, MD, PhD.

Publications

See Muller's publications via PubMed.

Featured Publications

The Muller Lab recently made two major discoveries in endothelial cell inflammatory signaling: identifying TRPC6 as the cation channel responsible for the endothelial cell calcium flux required for transmigration and describing the CD99 signaling pathway. Both had eluded discovery for decades.

• Watson, R.L., J. Buck, L.R. Levin, R.C. Winger, J. Wang, H. Arase, and W.A. Muller. 2015. Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration. J. Exp. Med. 212:1021-1041.
• Weber, E.W., F. Han, M. Tauseef, L. Birnbaumer, D. Mehta, and W.A. Muller. 2015. TRPC6 is the endothelial calcium channel that regulates leukocyte transendothelial migration during the inflammatory response. J Exp Med 212:1883-1899. PMID: 26392222

Contact

Bill Muller

Office

Ward Building, Room 3-126
303 E. Chicago Ave.
Chicago, IL 60611

Phone: 312-503-0436
Fax: 312-503-8249
Email: wamuller@northwestern.edu

Lab

Ward Building 3-070 and 3-031
Lab Phone: (312) 503-5200
Lab Fax: (312) 503-2630

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 Edward Thorp Lab studies the crosstalk between immune cells and the cardiovascular system and, in particular, within tissues characterized by low oxygen tension or associated with dyslipidemia, such as during myocardial infarction. In vivo, the lab interrogates the function of innate immune cell phagocytes, including macrophages, as they interact with other resident parenchymal cells during tissue repair and regeneration. Within the phagocyte, the influence of hypoxia and inflammation on intercellular and intracellular signaling networks and phagocyte function is studied in molecular detail. Taken together, our approach seeks to discover and link basic molecular and physiological networks that causally regulate disease progression and in turn are amenable to strategies for the amelioration of cardiovascular disease.

Publications

For additional information, visit the Thorp Lab site or see the faculty profile of Edward Thorp, PhD.

See Thorp's publications in PubMed.

Contact

Contact the Thorp Lab at 312-503-3140.

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.