Learn how people react to environmental triggers and how this reactivity can lead to chronic illness through the example of mold or chronic inflammatory response syndrome.
2. Systems Biology
Institute for Systems Biology.
Systemsbiology.org
“It is a holistic approach to deciphering the
complexity of biological systems that starts
from the understanding that the networks
that form the whole of living organisms are
more than the sum of their parts.”
3. Systems Biology
“It is not enough to understand only one part
of a system when studying the complexity of
biology.”
Institute for Systems Biology.
Systemsbiology.org
Network of Networks
“It is collaborative, integrating many
scientific disciplines … to develop solutions
to the world’s most pressing health and
environmental issues.”
5. Genetic Template
• “Home-biome”: a built environment:
• Nature’s contribution to the development of an
individual (Nature-vs-Nuture)
• Epigenetics:
• Environmental effects
• Transcriptomics
12. Somatobiome
The collection of living organisms present
across all the ecological niches of the body.
Gut Microbiome
Sinu-rhinobiome
Vasculo-biome
Dermo-biome
Vagino-biome
Pulmo-biome
17. Danger Responses: ANS
• Autonomic (Vegetative) Nervous System
• Sympathetic: Fight or Flight
• Parasympathetic: Restore and Repair
• Enteric: Gastrointestinal
• Other areas of importance:
• Vagal tone: Polyvagal Theory
• Limbic system: Cyclical Amplification
51. The Fab Five
Toxic mold
1. Aspergillus penicilloides
2. Aspergillus versicolor
3. Chaetomium globosum
4. Stachybotrys chartarum
5. Wallemia sebi
HERTSMI-2 testing
Just a few of many toxic molds
52. Stachybotrys chartarum
Toxic black mold
Stachybotrys
• Sticky spores being
released into the
atmosphere
• High humidity
required
From EPA’s mold brochure
Environ Health Perspect. 1999 Jun; 107(Suppl 3): 495–499. Overview of
investigations into pulmonary hemorrhage among infants in Cleveland,
Ohio. Dearborn, DG, et al.
54. Mold growth requirements
• Mold Spores
• Temperature
• Nutrient source
• Dry wall
• Framing
• Furniture, personal effects
• Moisture
The ONE thing we can control is
dampness
55. Water Damaged Buildings (WDB)
• 50% of all American buildings have
water damage (NIOSH, EPA)
• Acceptable humidity levels:
• < 55-60% < 30-45%
Summer Winter
56. WDB: Get out
• Find the source:
• Building history: leaks, floods, fire, dust
• Musty smells
• Visible mold (take a photo)
• Patterns of illness: timing
• Don’t forget cars
• At risk buildings: schools, rentals, dorms, hotels
• Testing
• Find a safe place
57. Safe Living
• Air Purification:
• Good quality air purifier
• Air purifiers
• Air cleaners/ozone
• Check humidity
• Humidity monitor (humidistat)
• Get dehumidifier and use as needed
58. Remediation
• Testing the environment:
• Mold DNA:
• HERTSMI-2: $155
• ERMI: $290
• Only tests that correlates with human health
• Mold spore trapping (air flow testing)
• Find the sources of moisture
• Remediate and Retest
• Removal of contaminated belongings
64. EAI: Danger Response
Immune Treatment
• Cytokine Production:
• Cytoquel
• Transfer Factor, Transfer Factor Enviro
• Innate Immune Response:
• Transfer Factor
• Auto-Immunity
• Transfer Factor
• Avoidance
• Mast cells
• Quercetin
• Ketotifen
65. Mitochondria and
Cytokine Production
• Targeting mitochondrial reactive oxygen species as novel
therapy for inflammatory diseases and cancers. Li et al.
Journal of Hematology & Oncology 2013, 6:19
• Cytokine production by mtROS:
• Activation of RIG-1-like receptors
• Inflammasome activation
• MAPK
67. Mitochondria: Source of DAMPS
• Mitochondrial constituents as DAMPs:
• Injection of mtDNA into joints induces inflammation and
arthritis
• Splenocytes exposed to mtDNA (not nDNA) increase
cytokine secretion
• mtDNA is released into circulation during trauma and shock
• Mitochondrial extracts (with mtDNA) cause systemic lung and
liver inflammation in vivo
68. Pattern Recognition Receptors
• TLR: Toll-like Receptors
• Transmembrane proteins, Interleukin-1 family
• Recognize bacterial, viral and fungal PAMPs, and DAMPs
• NLR: NOD-like Receptors
• Cytosolic receptors
• Recognize microbial PAMPs and DAMPs
• CLR: C-type Lectin Receptors
• Soluble and transmembrane proteins
• Recognize carbohydrate structures on pathogens
• RLR: RIG-1-like Receptors
• Cytosolic receptors in immune and non-immune cells
• Required for type I interferon and proinflammatory cytokine
production through NFKB in viral infections
Mitochondria in innate immune responses. West PA et al. Nat Rev
Immunol. 2011 Jun: 11(6): 389-402.
69. Mycotoxin Stimulation of Mitochondrial
DAMPS
• NLRP3 Inflammasome
• Member of NLR family
• Activates caspase 1, leading to pro-IL-1B, IL-18
• Increased ROS production may be critical for activation
• Trichothecene mycotoxins activate NLRP3
inflammasome through a P2X7 receptor and Src
tyrosine kinase dependent pathway. Kankkunen P
et al. Hum Immunol. 2014 Feb;75(2):134-40.
• Roridin A (WDB-mycotoxin) acts as microbial danger
signal
• Triggers activation of NLRP3 inflammasome in human
primary macrophages
70. Mitochondria and
Innate Immunity
• Centrally positioned for innate immune responses
• Enhanced crosstalk between metabolic and immune
pathways
• Augment host ability to sense microbial virulence
mechanism
71. TGF-β1 and
Mitochondrial Defects
• GSK3 inactivation is involved in mitochondrial
complex IV defect in transforming growth factor
(TGF) β1-induced senescence. Byun HO et al. Exp
Cell Res. 2012 Sep 10;318(15):1808-19.
• TGF-β1 stimulates mitochondrial oxidative
phosphorylation and generation of reactive
oxygen species in cultured mouse podocytes,
mediated in part by the mTOR pathway. Abe Y et
al. Am J Physiol Renal Physiol. 2013 Nov 15; 305(10):
F1477–F1490.
• Epithelial Cell Mitochondrial Dysfunction and
PINK1 Are Induced by Transforming Growth
Factor- Beta1 in Pulmonary Fibrosis. Patel A et al.
PLoS One. 2015; 10(3): e0121246.
