Immune Booster #9: Autoimmune diseases with Mark Shlomchik
Sep 10, 2024
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Dive into the fascinating world of autoimmune diseases as Mark Shlomchik shares his journey from medicine to impactful immunology research. Discover the pivotal role of B-cells and the breakthroughs in autoantibody understanding. The conversation uncovers the significance of mentorship and the art of scientific inquiry. Learn about innovative treatments like CAR T-cell therapy and the challenges faced in research. Lastly, enjoy a glimpse into personal passions, including music and baking, emphasizing the creativity in science.
Mark Shlomchik's unconventional career journey highlights the significance of following true interests and being open to career changes in science.
His research on autoreactive B-cells and TLRs reveals the complexities of autoimmunity, challenging previous assumptions about immune response mechanisms.
Deep dives
The Journey into Immunology
The speaker shares an unconventional path into science, initially pursuing a medical degree but discovering a passion for immunology during medical school. The transformative moment came during an immunology course, where the teaching style and the challenge of experimental design captured their interest. A pivotal conversation with a professor led to taking a year off to work in a lab, ultimately solidifying the decision to pursue a PhD instead. This journey highlights the importance of recognizing one's true interests and being open to changing career trajectories.
Contributions to B-Cell Research
The discussion centers on significant contributions to B-cell biology, particularly in understanding autoreactive B-cells and autoimmunity. Key findings indicated that autoreactive B-cells are clonally expanded and undergo somatic hypermutation, challenging previous assumptions about autoimmunity being merely overactive immune responses. By creating transgenic mouse models, the speaker explored the life cycle and activation of autoreactive B-cells in autoimmune environments. These findings revolutionized the understanding of autoimmunity, showing that chronic stimulation, similar to viral responses, drives the activation of these cells.
The Role of Toll-like Receptors
The conversation delves into the exploration of Toll-like receptors (TLRs) and their unexpected roles in autoimmune responses. Initial research indicated that TLRs, particularly TLR9, were thought to exacerbate conditions like lupus, contradicting expectations that inhibiting them would lead to improved outcomes. Experiments demonstrated that the absence of TLR9 led to worsened disease severity, while knocking out TLR7 alleviated symptoms, revealing a complex relationship between TLRs and autoimmune pathogenesis. This ongoing research underscores the necessity for nuanced understanding in immunology, where traditional models of receptor function do not always apply.
From the American Association of Immunologists 2024 conference in Chicago, Cindy and Steph meet up with Mark Shlomchik to talk about his career and the research of his laboratory on systemic autoimmune diseases, long-lived B cell immunity, and immunopathogenesis.