Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).

Infectious diseases remain one of the leading causes of morbidity and mortality in the United States and worldwide. The Coers lab seeks to understand fundamental aspects of the immune response to microbes as well as the corresponding immune evasion strategies evolved by human pathogens to undermine immunity and establish infections. Defining human immunity and microbial counter-immunity pathways on a molecular level will provide roadmaps for the rational design of novel antimicrobial therapies and improved vaccine strategies against human pathogens such as the enteric bacterial pathogen Shigella or the sexually transmitted bacterial pathogen Chlamydia.

In addition to making major inroads in the fields of immunity, inflammation and microbial pathogenesis, our second, but equally important goal, is to train the next generation of scientists in an environment that prioritizes excellence, research integrity, learning opportunities, and teamwork. We strive to create an environment of mutual respect, openness, collegiality, integrity and, last but not least, fun, which promotes and awards curiosity and fosters collaborations.

We study the pathways by which microorganisms cross cellular barriers and the mechanisms by which these barriers restrict microbial infections. Our studies primarily focus on the epithelium that lines the gastrointestinal tract and on placental trophoblasts, the cells that comprise a key cellular barrier of the human placenta. Our work is highly multidisciplinary and encompasses aspects of cell biology, immunology, and microbiology. Our long-term goals are to identify pathogen- and host-specific therapeutic targets to prevent or treat microbial infections and ultimately to alleviate the morbidity and mortality caused by these infections.

Liton’s lab is focused on investigating a potential relationship between impairment of the autophagy lysosomal pathway and glaucoma in the aging eye. 

Dr. Meyer studies the effects of toxic agents and stressors on human and wildlife health. He is particularly interested in understanding the mechanisms by which environmental agents cause DNA damage, the molecular processes that organisms employ to protect prevent and repair DNA damage, and genetic differences that may lead to increased or decreased sensitivity to DNA damage. Mitochondrial DNA damage and repair, as well as mitochondrial function in general, are a particular focus. He studies these effects in the nematode Caenorhabditis elegans, in cell culture, and collaboratively in other laboratory model organisms as well as in human populations in the USA and globally.

Shinohara Lab Website

Immune responses against pathogens are essential for host protection, but excessive and uncontrolled immune reactions can lead to autoimmunity. How does our immune system keep the balance fine-tuned? This is a central question being asked in my laboratory.

The immune system needs to detect pathogens quickly and effectively. This is performed by the innate immune system, which includes cells such as macrophages and dendritic cells (DCs). Pathogens are recognized by pattern recognition receptors (PRRs) and may be cleared in the innate immune system. However, when pathogens cannot be eliminated by innate immunity, the adaptive immune system participates by exploiting the ability of T cells and B cells. The two immune systems work together not only to clear pathogens effectively but also to avoid collateral damages by our own immune responses. 

In my lab, we use mouse models for infectious and autoimmune diseases to understand the cellular and molecular mechanisms of; pathogen recognition by PRRs in macrophages and DCs, initiation of inflammatory responses in the innate immune system, and the impact of innate immune inflammation on the development and regulation of T cell-mediated adaptive immune responses. 

Several projects are ongoing in the lab. They are to study (1) the roles of PRR in EAE (an animal model of multiple sclerosis), (2) the interplay between immune cells and CNS (central nervous system)-resident cells during EAE and fungal infection, (3) protective and pathogenic mechanisms of immune cells in the lung during fungal infection and inflammation, and (4) the roles of a protein termed osteopontin (OPN), as both secreted (sOPN) and intracellular (iOPN) isoforms, in regulation of immune responses . Although we are very active in EAE to study autoimmunity, other mouse models, such as graft-versus-host disease (GvHD) is ongoing. Cell types we study are mainly DCs, macrophages, neutrophils, and T cells. 

My lab uses mouse genetic modeling and molecular and cellular techniques to study basic biochemical pathways of relevance to aging biology.

I. Aging is often accompanied by increases in inflammation. A major interest of the lab is how perturbations in the regulation of autophagy and mitochondrial dynamics in cells are linked to inflammation. One project in the lab focuses on a family of interferon-gamma and LPS regulated proteins, the Immunity Related GTPases (IRGs). The lab has shown that mice and cells lacking one of these proteins, Irgm1, have excessive inflammatory responses that are accompanied by decreases in autophagy and mitophagy, and altered cellular metabolism. IRG genes in human (IRGM) have been linked to several inflammatory diseases including Crohn’s disease and sepsis. Current work in the lab focuses on their role in those diseases using bacterial and relevant mouse models.

II. Altered expression of the cytokine Transforming Growth Factor beta (TGF-b) has been linked with a number of aging processes, including stem cell and neural function. TGF-b is consequently a therapeutic target for a number of age-related diseases. The lab is studying a novel regulator of TGF-b expression called P311, which drives TGF-b translation. Mice have been created that lack P311 and are being used to address the role of P311 in a number of physiological processes.

Jianbo earned his Ph.D. in Pharmacology from Pennsylvania State University, followed by postdoctoral training at Stanford University. He then started his independent academic career at the University of Hong Kong and City University of Hong Kong, prior to his appointment at DKU. His laboratory focuses on cell signaling and drug discovery, with research interests spanning autophagy, endosomal trafficking, metastasis, anticancer immunity, as well as the roles of calcium ions (Ca2+) and reactive oxygen species (ROS).