Mitochondria are multi-faceted organelles integral to many processes including energy generation, programmed cell death, signal transduction, and immunity. Consequently, mitochondrial stress can drastically alter cell and tissue function and is increasingly implicated in aging, neurodegenerative diseases, cardiovascular diseases, inflammatory disorders, and cancer. Research in the West Lab centers on understanding how mitochondria regulate innate immunity and inflammatory processes to influence human health and disease.
MITOCHONDRIAL CONTROL OF INNATE IMMUNITY & INFLAMMATION
Mitochondria are critical participants in innate immunity and have emerged as key regulators of inflammation. We are currently exploring the signaling pathways linking mitochondria to innate immunity, with the ultimate goal of characterizing how these pathways influence the inflammatory pathology of primary mitochondrial diseases, cardiovascular diseases, and neurological disorders such as Gulf War Illness. (Supported by grants from the DoD and NIH)
MODULATION OF MITOCHONDRIAL FUNCTION BY PATHOGENS
Many viral and bacterial pathogens target mitochondria to rewire cellular metabolism and interfere with innate immunity. Defining the microbial effector mechanisms used to manipulate these organelles could reveal new therapeutic avenues to limit virulence and boost host immunity. We are therefore collaborating with labs across campus to define how viral and bacterial pathogens alter mitochondrial function and dynamics. (Support from the DoD and Human Herpes Virus-6 Foundation)
MITOCHONDRIAL DYSFUNCTION & IMMUNE REWIRING IN CANCER
Alterations in mitochondrial function and cellular metabolism have long been recognized as hallmarks of cancer. Moreover, mitochondrial genome instability has been observed in many aggressive cancers including melanoma, and recent reports indicate that mitochondrial DNA (mtDNA) dysfunction can engage stress signaling responses to enhance tumor growth and invasion. We utilize a physiologically relevant mouse model of metastatic melanoma and patient-derived melanoma cell lines to explore how mitochondrial stress and mtDNA instability influence the development and progression of this cancer. We are particularly interested in defining how mitochondrial dysfunction modulates innate and adaptive immunity in the melanoma microenvironment to shape anti-tumor immune responses. (Supported by the Cancer Prevention and Research Institute of Texas (CPRIT))
All images were acquired by the West lab. Descriptions from top to bottom:
Mitochondrial dynamics in real time. Mouse fibroblast expressing mito-GFP was imaged live on a Zeiss LSM 800 confocal system.
Human Herpes Virus-6 infection cause mitochondrial fragmentation. Human T-lymphoblast cell infected with HHV-6 (co-stained with antibodies against mitochondria (red, green) & HHV-6 p41 antigen (violet)).
Mitochondrial fission in a murine melanoma cancer cell captured by transmission electron microscopy.