JUL 29, 2020 12:00 PM EDT

Linking Cancer Metabolism to Neurodegeneration

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • David W. Cugell Professor of Medicine, Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago
    Biography
      I received a BA in mathematics (1991) followed by a Ph.D. in Cell Physiology (1996) at the University of Chicago with Dr. Paul Schumacker, Then did my post-doctoral fellowship jointly with Dr. Paul Schumacker and Dr. Craig Thompson (1999). I started my lab in 2000 at Northwestern University Feinberg School of Medicine. My lab has made contributions to understanding the function of mitochondria. For decades, the mitochondria have been primarily viewed as biosynthetic and bioenergetic organelles generating metabolites for the production of macromolecules and ATP, respectively. We have elucidated mitochondria have a third distinct role whereby they participate in cellular signaling processes through the release of reactive oxygen species (ROS) and the metabolite L-2hydroxyglutrate (L-2HG). Our work has implicated the necessity of mitochondrial ROS as second messengers for multiple biological processes including hypoxic activation of HIF dependent gene transcription, cellular differentiation, and immune cell activation. We have also identified that mitochondria release the metabolite L-2HG, which increases histone and DNA methylation to control hematopoietic stem cell (HSC) differentiation and regulatory T cell (Treg) function, respectively. Thus, mitochondria serve as signaling organelles. In the field of cancer, our work established that mitochondrial metabolism and ROS is necessary for tumorigenesis in vivo. Previously, the prevailing idea was that increased aerobic glycolysis (i.e. Warburg effect) was the dominant metabolic reprogramming event in cancer cells. This led to our current understanding that both aerobic glycolysis and mitochondrial metabolism are essential for tumor growth. I have also published a book entitled "Navigating Metabolism" (Cold Spring Harbor Press, 2015).

    Abstract

    The major function of mitochondria in cellular homeostasis has been the generation of ATP through oxidative phosphorylation. However, we have previously demonstrated that mitochondria can serve as signaling organelles by releasing low levels of reactive oxygen species (ROS) that are essential for hypoxic activation of HIF, antigen activation of T cells, cellular differentiation and proliferation of cancer cells. Our recent findings indicate that mitochondria also release TCA cycle metabolites that are necessary for chromatin and DNA modifications. We will present our current findings on how mitochondria affect cellular function beyond ATP production through ROS and TCA cycle metabolites in controlling cancer and brain metabolism.

     

    Learning Objectives:

    Discover:

    1. Mechanisms for mitochondria to act as signaling organelles.

    2. The role of mitochondria in the TCA cycle and chromatin and DNA modifications.

    3. How mitochondria affect cellular function beyond ATP production through ROS and TCA cycle metabolites in controlling cancer and brain metabolism.


    Show Resources
    You May Also Like
    FEB 24, 2021 10:00 AM PST
    C.E. CREDITS
    FEB 24, 2021 10:00 AM PST
    DATE: February 24, 2021 TIME: 10am PST Automated lab instruments such as liquid handlers and cell sorters are increasingly common in all types of laboratories, driving fast results for labor...
    DEC 03, 2020 4:30 PM PST
    C.E. CREDITS
    DEC 03, 2020 4:30 PM PST
    This drug development program is designed to create a family of broad-spectrum, pan-coronaviral drugs that respectively inhibit multiple key enzymes required for viral replication. By target...
    JAN 21, 2021 8:00 AM PST
    JAN 21, 2021 8:00 AM PST
    Date: January 21, 2021 Time: 8:00am (PST), 11:00am (EST) Today, critical reagent characterization is a key component in the overall workflow to establish robust ligand binding assays (e.g.,...
    NOV 19, 2020 8:00 AM GMT
    C.E. CREDITS
    NOV 19, 2020 8:00 AM GMT
    Date: November 19, 2020 Time: 12:00am (PDT), 9:00am (CET), 4:00pm (SGT) We present split-FISH, a multiplexed fluorescence in situ hybridization method that leverages a split-probe design to...
    NOV 18, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 18, 2020 8:00 AM PST
    DATE: November 18, 2020 TIME: 08:00am PDT We develop and implement technologies to solve some of the major bottlenecks in biomedical research. In particular, we establish new imaging approac...
    MAR 30, 2021 8:00 AM PDT
    MAR 30, 2021 8:00 AM PDT
    DATE: March 30, 2021 TIME: 08:00am PST In this talk, we will discuss the value of moving towards modular and automated, closed-system technologies designed to enable scalable and cost-effect...
    Loading Comments...
    Show Resources