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Mitochondria in Complex Diseases

Mitochondria in Complex Diseases

Tuesday, April 21, 2020, 8:30 AM - 6:00 PM

The New York Academy of Sciences, 7 World Trade Center, 250 Greenwich St Fl 40, New York

Presented By

The New York Academy of Sciences

 

Mitochondria in Complex Diseases will explore the impact of these cellular powerhouses in physiology and medicine. Beyond their well-known function as the regulator of cellular energy metabolism, mitochondria also function in cellular signaling, differentiation, cell death, regulating the cell cycle and cell growth, reactive oxygen species generation, and regulation of the epigenome. Speakers at this symposium will explore new advances in the basic biology of mitochondria, and highlight the role of mitochondrial damage and dysfunction in cardiovascular disease, immunology, regenerative medicine, neurodegenerative disease, and aging.

Registration

Member
By 03/09/2020
$90
After 03/09/2020
$130
Nonmember Academia, Faculty, etc.
By 03/09/2020
$180
After 03/09/2020
$260
Nonmember Corporate, Other
By 03/09/2020
$250
After 03/09/2020
$350
Nonmember Not for Profit
By 03/09/2020
$180
After 03/09/2020
$260
Nonmember Student, Undergrad, Grad, Fellow
By 03/09/2020
$100
After 03/09/2020
$145
Member Student, Post-Doc, Fellow
By 03/09/2020
$50
After 03/09/2020
$70
Earlybird Registration:
17
days
left
Deadline:
0
days
left

Scientific Organizing Committee

Carla Koehler, PhD
Carla Koehler, PhD

University of California, Los Angeles

Lisa Norquay, PhD
Lisa Norquay, PhD

Janssen Research and Development

Gerald Shadel
Gerald Shadel, PhD

Salk Institute

Douglas C. Wallace, PhD
Douglas C. Wallace, PhD

Children’s Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania

Alison Carley, PhD
Alison Carley, PhD

The New York Academy of Sciences

Sonya Dougal, PhD
Sonya Dougal, PhD

The New York Academy of Sciences

Keynote Speaker

E. Dale Abel
E. Dale Abel, MD, PhD

University of Iowa

Speakers

Estela Area-Gomez, PhD
Estela Area-Gomez, PhD

Columbia University Irving Medical Center

Vilhelm Bohr
Vilhelm A. Bohr, MD, PhD

National Institute on Aging, National Institutes of Health

Jerry Chipuk
Jerry Chipuk, PhD

Icahn School of Medicine at Mount Sinai

Michel Desjardins, PhD
Michel Desjardins, PhD

Universite de Montreal

Leanne Jones, PhD
Leanne Jones, PhD

University of California, Los Angeles

Ruth Slack, PhD
Ruth Slack, PhD

University of Ottawa Brain and Mind Research Institute

A. Phillip West, PhD
A. Phillip West, PhD

Texas A&M University

Eileen White, PhD
Eileen White, PhD

Rutgers Cancer Institute of New Jersey, Rutgers University

Tuesday

April 21, 2020

8:30 AM

Continental Breakfast and Registration

9:00 AM

Introduction and Welcome Remarks

9:15 AM

Mitochondrial Dynamics and Cardiometabolic Disease

Speaker

E. Dale Abel, MD, PhD
University of Iowa

Mitochondria are the metabolic powerhouses of cells. In addition to generating ATP, they play important roles in cell survival pathways such as apoptosis and necrosis. Mitochondrial size and shape are dynamically regulated by a process known as mitochondrial dynamics.Mitochondrial dynamics are regulated by a family of proteins that regulate mitochondrial fusion (mitofusins and optic atrophy 1) and mitochondrial fission (Drp1 and Fis1). The significance of mitochondrial dynamics in metabolically active cells such as skeletal and cardiac muscle are only now beginning to be elucidated. In cardiac muscle, mitochondrial dynamics plays an important role in mitochondrial quality control and defects in regulatory pathways that govern these processes leads to heart failure. In response to nutrient excess such as lipid overload, as occurs in diabetes, mitochondrial shape and morphology are altered by effects of nutrient stress and oxidative stress on mitochondrial dynamics signaling pathways, which have important implications for understanding mitochondrial dysfunction in diabetic cardiomyopathy. Moreover, mitochondrial dynamics regulates crosstalk between mitochondria and other organelles such as the endoplasmic reticulum that may regulate the generation of hormones such as fibroblast growth factor 21 (FGF-21), with potent anti-diabetic and anti-obesity effects. Finally, recent insights linking mitochondrial dynamics proteins in platelets and the estrogen-mediated modulation of athero-thrombosis will be presented and discussed.

10:00 AM

Imbalances in Type I Interferon and Nrf2 Signaling Drive Myeloid Reprogramming and Tissue Dysfunction in a Model of Mitochondrial DNA Disease

Speaker

Phillip West, PhD
Texas A&M University

Mitochondrial dysfunction has emerged as an important driver of deleterious inflammatory and interferon responses in numerous human diseases. However, it remains unclear whether alterations in mitochondria-innate immune crosstalk contribute to the pathobiology of mitochondrial diseases. Using a model of Polymerase gamma (POLG)-related mitochondrial disease, we have uncovered that mitochondrial DNA (mtDNA) instability in POLG-mutant mice engages DNA sensors of the innate immune system, leading to the sustained and systemic expression of type I interferon (IFN-I) responses that increase with age.Furthermore, chronic IFN-I signaling dramatically augments myeloid cellpopulations in the bone marrow and blood, heightening secretion of inflammatory cytokines after stimulation and markedly increasing susceptibility to lethal septic shock. Mechanistically, potentiated IFN-I signaling in POLG-mutants suppresses the activation and nuclear localization of the transcription factor Nrf2, a key regulator of antioxidant and anti-inflammatory responses, causing increased oxidative damage,sustained inflammatory cytokine secretion, and accelerating metabolic dysfunction.Finally, ablation of IFN-I signaling attenuates some aspects of tissue pathology in POLG-mutant mice by boosting Nrf2-mediatedantioxidant responses and reducing hyper-inflammatory phenotypes of these animals. These findings further advance our understanding of how mitochondrial dysfunction shapes innate immunity and may have implications for managing immunopathology in patients with POLG-related diseases or other mitochondrial disorders.

10:30 AM

To be announced

Speaker

Michel Desjardins, PhD
Universite de Montreal
11:00 AM

Coffee Break

11:30 AM

Mitochondria as Regulators of Neural Stem Cell Fate in Neurodegeneration

Speaker

Ruth Slack, PhD
University of Ottawa Brain and Mind Research Institute
12:00 PM

The Role of Mitochondrial Dynamics in Tissue Stem Cells

Speaker

Leanne Jones, PhD
University of California, Los Angeles
12:30 PM

Networking Lunch and Poster Session

2:00 PM

Mitochondrial Dysfunction as a Consequence of Nuclear DNA Damage

Speaker

Vilhelm A. Bohr, MD, PhD
National Institute of Aging, National Institutes of Health

We find that some DNA repair defective diseases with severe neurodegeneration have mitochondrial dysfunction. Our studies involve cell lines, the worm (c.elegans), and mouse models and include the premature aging syndromes Xeroderma pigmentosum group A, Cockaynes syndrome, Ataxia telangiectasia and Werner syndrome. We find a pattern of hyperparylation, deficiency in the NAD+ and Sirtuin signaling and mitochondrial stress. We are pursuing mechanistic studies of this signaling and interventions at different steps to improve mitochondrial health and neurodegeneration. I will discuss intervention studies in these disease models including a new Alzheimer mouse model using NAD supplementation. NAD supplementation stimulates mitochondrial functions including mitophagy and stimulates DNA repair pathways. Based on human postmortem material and IPSC cells we identify mitophagy defects as a prominent feature in Alzheimers disease (AD). Using c.elegans AD models we screened for mitophagy stimulators and identified compounds that subsequentially also show major improvement of AD features in mouse models.

2:30 PM

Mitochondria Contact Sites in Neurodegeneration

Speaker

Estela Area-Gomez, PhD
Columbia University Irving Medical Center
3:00 PM

Coffee Break

3:30 PM

Mitochondrial Division and Cancer: Causes, Consequences, and Coincidence

Speaker

Jerry Chipuk, PhD
Icahn School of Medicine at Mount Sinai

Mitochondrial division is essential for mitosis and metazoan development, and the impact of mitochondrial division in cancer has recently become apparent. Here, we examine the direct effects of oncogenic RASG12V mediated cellular transformation on the mitochondrial dynamics machinery and observe a positive selection for dynamin related protein 1 (DRP1), a protein required for mitochondrial network division. Loss of DRP1 prevents RASG12V-induced mitochondrial dysfunction, and renders cells resistant to transformation. Conversely, in human tumor cell lines with activating MAPK mutations, inhibition of these signals leads to robust mitochondrial network reprogramming initiated by DRP1 loss resulting in mitochondrial hyper-fusion and increased mitochondrial metabolism. These phenotypes are mechanistically linked by ERK1/2 phosphorylation of DRP1 serine 616; DRP1S616 phosphorylation is sufficient to phenocopy transformation-induced mitochondrial dysfunction, and DRP1S616 phosphorylation status dichotomizes BRAFWt from BRAFV600E positive lesions and informs which patients should be monitored more frequently for melanomagenesis. At present, we are investigating the implications of chronic mitochondrial division in oncogene-induced senescence, the mitochondrial unfolded protein response, and the immunobiology of melanoma in situ.

4:00 PM

To be announced

Speaker

Eileen White, PhD
Rutgers Cancer Institute of New Jersey, Rutgers University
4:30 PM

Panel Discussion

5:00 PM

Closing Remarks

5:15 PM

Networking Reception

6:15 PM

Adjourn