bad news with a side of good news
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Bad News with a side of Good news. Genetic Syndromes Teratogens Endocrine disruption Cancer Anti-angiogenesis treatment Induced Pluripotent Stem Cells Regenerative Biology. A New Hope. Phantom Menace. Attack of the Clones. Lucky to be here!. 17.1. Better to be lucky than good?. - PowerPoint PPT PresentationTRANSCRIPT
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Bad News with a side of Good news• Genetic Syndromes• Teratogens• Endocrine disruption• Cancer
• Anti-angiogenesis treatment• Induced Pluripotent Stem Cells• Regenerative Biology
A New Hope
Phantom Menace
Attack of the Clones
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Lucky to be here!
17.1
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Better to be lucky than good?
occasionally livea short time
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Nondisjunction
Fig 16.4
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Human Syndromes• Mosaic pleiotropy• Relational pleiotropy• Genetic and Phenotypic
heterogeneity.
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Teratogenesis• DDT- pesticide• Thalidomide- sedative during
pregnancies• Rubella- 1964 epidemic leading
to 20,000 blind, deaf, or both fetuses.
DDT
Thalidomide
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Timing is everything
Fig. 17.5
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Teratogens
• Table 17.2
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Alcohol• Fetal Alcohol Syndrome
(FAS)– 1 out of 650 children
• Fetal alcohol Spectrum Disorder (FASD)– 3 times as many kids with
FASD than FAS
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Retinoic Acid• Accutane: 13-cis-retinoic acid
• Hox gene expression• Pharyngeal Arches
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Endocrine disruptors• Hormonal
Agonists/Antagonists• Block Synthesis, elimination
and transportation of hormones
• Prime organism to be more sensitive to hormones
PCBs
Diethylstibestrol (DES)
Bisphenol A (BPA)
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Diethylstibestrol (DES)• Gonad Development• Hoxa10 regulation• Guess who? BMP or Wnt?
17.9 then 17.11, then 17.12
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Plastic bottles a source of teratogens?
• Nonylphenol
• Bisphenol A
Fig. 16.22 and 16.25
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Nonylphenol• Tufts University- estrogen
responsive tumor cells• Plastic containers that held
water and serum were culprit.
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Bisphenol A (BPA)• Developed as a synthetic
estrogen• 2 Billion Pounds still
produced yearly• Used for:
– Resin lining in most cans– Polycarbonate plastic in baby
bottles, childrens toys– Dental sealant. – Brightly colored polycarbonate
bottles• Water in Polycarbonate
bottles for week at Room Temp.– 300 mg per liter of BPA
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Bisphenol A (BPA)• Low dose exposure
– Meiotic defects• Predispostion to breast
cancer• 95% of individuals tested in
U.S. and Japan have measurable amounts of BPA in urine
• Plastics industry claims “evidence is meager”
• Nalgene and Wal-Mart no longer make or sell BPA containing bottles.
Figure 17.13 and 17.14
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Other teratogens• Heavy Metals• Pathogens
– Rubella- within first 6 weeks– Toxoplasma gondii
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Cancer: a disease of development• Context dependent tumors
– Cell-cell communication– Paracrine pathways
• Cancer Stem cell hypothesis– MITF and melanocytes
• Embryonic migration pathways
• Epigenetic reprogramming
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Cancer Stem Cell Hypothesis
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Cancer: a disease of development• Context dependent tumors
– Cell-cell communication– Paracrine pathways
• Cancer Stem cell hypothesis– MITF and melanocytes
• Embryonic migration pathways
• Epigenetic reprogramming
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Cancer: Epigenetic reprogramming
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Cancer: Epigenetic reprogramming
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Light at end of tunnel..• Anti-Angiogenesis• Stem cells and tissue
regeneration
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Anti-Angiogenesis• VEGFs• Fgfs
17.22
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Embryonic Stem Cells• Embryonic stem cells• Embryonic germ cells
17.23
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Induced Pluripotent stem cells• Fbx15 enhancer• OCT4, SOX2, c-MYC, and KLF4
17.25
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Induced Pluripotent stem cells• Use of viral vectors• Inject fibroblasts transduced with OCT4, SOX2, KLF4, and c-
MYC.
17.26