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
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?
occasionally livea short time
Nondisjunction
Fig 16.4
Human Syndromes• Mosaic pleiotropy• Relational pleiotropy• Genetic and Phenotypic
heterogeneity.
Teratogenesis• DDT- pesticide• Thalidomide- sedative during
pregnancies• Rubella- 1964 epidemic leading
to 20,000 blind, deaf, or both fetuses.
DDT
Thalidomide
Timing is everything
Fig. 17.5
Teratogens
• Table 17.2
Alcohol• Fetal Alcohol Syndrome
(FAS)– 1 out of 650 children
• Fetal alcohol Spectrum Disorder (FASD)– 3 times as many kids with
FASD than FAS
Retinoic Acid• Accutane: 13-cis-retinoic acid
• Hox gene expression• Pharyngeal Arches
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)
Diethylstibestrol (DES)• Gonad Development• Hoxa10 regulation• Guess who? BMP or Wnt?
17.9 then 17.11, then 17.12
Plastic bottles a source of teratogens?
• Nonylphenol
• Bisphenol A
Fig. 16.22 and 16.25
Nonylphenol• Tufts University- estrogen
responsive tumor cells• Plastic containers that held
water and serum were culprit.
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
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
Other teratogens• Heavy Metals• Pathogens
– Rubella- within first 6 weeks– Toxoplasma gondii
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
Cancer Stem Cell Hypothesis
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
Cancer: Epigenetic reprogramming
Cancer: Epigenetic reprogramming
Light at end of tunnel..• Anti-Angiogenesis• Stem cells and tissue
regeneration
Anti-Angiogenesis• VEGFs• Fgfs
17.22
Embryonic Stem Cells• Embryonic stem cells• Embryonic germ cells
17.23
Induced Pluripotent stem cells• Fbx15 enhancer• OCT4, SOX2, c-MYC, and KLF4
17.25
Induced Pluripotent stem cells• Use of viral vectors• Inject fibroblasts transduced with OCT4, SOX2, KLF4, and c-
MYC.
17.26