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?.

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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?

occasionally live

a 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

Bisphenol A (BPA)

Diethylstibestrol (DES)


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)

Figure 17.13 and 17.14

  • 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.


Other teratogens

  • Heavy Metals

  • Pathogens

    • Rubella- within first 6 weeks

    • Toxoplasmagondii


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


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