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Personalized Medicine. Hope or Hype?. Diagnosing inherited forms of breast cancer: Up close and personal. Up to 10% of breast cancer can be shown to be inherited and most of these cancers are traceable to mutations in the BRCA1 or BRCA2 genes. Denise- patient.
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Personalized Medicine. Hope or Hype?
Diagnosing inherited forms of breast cancer:Up close and personal Up to 10% of breast cancer can be shown to be inherited and most of these cancers are traceable to mutations in the BRCA1 or BRCA2 genes. Denise- patient http://www.dnai.org/d/index.html Genes and Medicine, Applications, gene testing, Denise, “Decision to have her breasts removed”. …Barbara Weber,”Seeing who has the marker”. Dr. Barbara Weber- clinician and scientist
Decision… original source - DNAi site: Genes and Medicine, gene testing, Denise, “Decision to have her breasts removed”.Barbara Weber,”Seeing who has the marker”.
Seeing who has the marker… original source - DNAi site: Genes and Medicine, gene testing, Denise, “Decision to have her breasts removed”.Barbara Weber,”Seeing who has the marker”.
The science behind the medicine http://www.dnai.org/d/index.html. Applications, Genes and Medicine, gene hunting, Markers animation. Applications, Genes and Medicine, gene testing, making a pedigree animation. Applications, Genes and Medicine, gene testing, Testing for BRCA1 and BRCA2 animation
Marker Animation http://www.dnai.org/d/: Applications, Genes and Medicine, gene hunting, Markers animation.
Making a Pedigree http://www.dnai.org/d/: Applications, Genes and Medicine, gene testing, making a pedigree animation.
Testing for BRCA1 and BRCA2 http://www.dnai.org/d/: Applications, Genes and Medicine, , gene testing, Testing for BRCA1 and BRCA2 animation
The end of the story http://www.dnai.org/d/index.html. Genes and Medicine, Applications, gene testing, Denise, “Was she at increased risk” and “Finding out”. What would you have done if you were Denise or a member of her family? Remember that this gene was passed down from a male ancestor and males have higher cancer rates if they carry these genes.
Was she at increased risk http://www.dnai.org/d/index.html. Genes and Medicine, Applications, gene testing, Denise, “Was she at increased risk”
Finding out http://www.dnai.org/d/index.html. Genes and Medicine, Applications, gene testing, Denise, “Finding out”
New Frontiers: Personalized Medicine. Hope or Hype? Individual genome sequencing “Imagine the day when you and your doctor sit down to review a copy of your own personal genome. This vital information about your biology will enable your physician to inform you of your disease susceptibilities, the best ways to keep yourself healthy and how to avoid or lessen the impact of future illnesses.” http://genomics.xprize.org/
Why whole genome sequencing? •Require full functional understanding. Government genome project was a man and a woman from Buffalo. Celera was Craig Venter’s genome. Am I the same as them? • So sequencing was selective and missed: -personal mutations -regulatory mutations in noncoding sequence -repetitive sequences because they are difficult to sequence
The phase problem? Does the linear arrangement along the length of a chromosome have an impact in addition to the genotype? Is the upper arrangement “better” than the lower one? Are there “cis” effects in the arrangement of the genes on chromosomes?
“Personal DNA” Neil DeGrasse Tyson Nova Science Now copy of the 2010 commencement speech
“Personal DNA” Neil DeGrasse Tyson Local copy youtube fragment within the whole PBS program
The Promises of Personalized Medicine •Provide advanced screening for disease. •Select safer, more effective medications and dosages. •Generate better vaccines. Develop vaccines made of genetic material. These would activate immune system w/o causing infection. Inexpensive, stable, easy to store. Engineered to carry several strains of a pathogen at once. Develop cell-based vaccines. •Lower healthcare costs. Proactive lifestyle changes, early detection & treatment. Decrease adverse drug reactions. Decrease # medications, length of time on medication.
Are We There Yet? Reality Check. •Field of personalized medicine is in its infancy. •Access to personal genome is a long way off , or maybe not. $5000 genome by 2009 – Complete Genomics •For personalized medicine to be realized will require that we greatly reduce the cost and increase the speed of human genome sequencing. •This is the goal of the Archon X PRIZE for Genomics.
Personalized Medicine: Genomics and Stem Cell therapies. Genomics: Example: Cancers – Tumor genotyping 2009 Science 326, 218-220. lung cancer non-small cell lung cancer most common EML4-ALK fusion others: mutations in EGFR, Iressa Genotype every lung cancer. Check for array of mutations. Target drug therapy based on specific genes mutated 15-20% of patient tumors can be matched to specific drug. Reality: better initially, then cancers develop resistance. NCI: The Cancer Genome Atlas 20 cancer types, 5 years, $275 million in first 2 years.
Disease Targets for Intervention. • ALS – Amyotrophic Lateral Sclerosis • Huntington’s Disease • Type I Diabetes • Cancers • High Blood Pressure • Mental Illnesses • Asthma •Many are the same diseases that are targeted for stem cell therapies. • Cell therapies also referred to as regenerative medicine.
NIH Stem Cell Information: http://stemcells.nih.gov/
Video: Stem Cell PrimerNova Science Now Original source Local copy
What are stem cells and why are they important? Three important characteristics: 1. Capable of dividing to renew themselves for long periods. proliferation through mitosis long-term self-renewal 2. Unspecialized or undifferentiated. 3. Can be induced to differentiate. blood, heart muscle, nerve, etc. BUT, what are the signals that prevent differentiation during the self-renewal divisions? This is a key question! University of Wisconsin
There are two main types of stem cells. 1. Embryonic stem cells. derived from embryos in vitro fertilized eggs 2. Adult stem cells. population in every tissue typically generate same type of differentiated cells. originally thought NOT to be pluripotent Recent experiments have revealed -hematopoietic stem cells of bone marrow can be induced to form neurons and heart muscle. -liver stem cells induced to produce insulin. University of Wisconsin
How Are Human Embryonic Stem Cells Obtained? •Cleavage-stage embryo produced by in vitro fertilization. •~5 days to reach blastocyst stage. • Identify specific surface markers found only on undifferentiated ES cells. These surface markers change once cells begin to differentiate.
In suspension culture, hES cells differentiate. multicellular aggregate ⇩ gelatinized solid medium ⇩ differentiate further
2007: Shinya Yamanaka’s lab & James Thomson’s lab Genes for reprogramming differentiated cells to iPS cells. •Using retroviruses as carriers 4 human genes were identified that could cause a differentiated cell to be reprogrammed as an induced pluripotent cell (Oct3/4, Sox2 with Klf4 and c-Myc) when introduced simultaneously with the virus. •Oct3/4 & Sox2: Master transcriptional regulators. •Klf4 & c-Myc are required to increase induction efficiency. HOWEVER, Viral vectors increase the risk of tumorigenicity. c-Myc is an oncogene. ~20% mice develop tumors. http://en.wikipedia.org/wiki/Induced_pluripotent_stem_cells S. Yamanaka. 2009. Cell 137, 13-17.
2008: Generation of Induced Pluripotent Stem Cells without viral vectors. Shinya Yamanaka’s lab: single plasmid Expresses c-Myc plus cDNAs for Oct3/4, Sox3, Klf4 Transfection in mice. iPS cells without plasmid integration. Produced teratomas when transplanted into mice. Produced adult chimeras. Used embryonic fibroblasts. 2008 Science 322, 949-53
Generation and application of iPS Cells S. Yamanaka 2009
Movies Neil Theise CBS January 23, 2009 Where America Stands: Stem Cell Research CBS March 16, 2010
Video: Neil Theise CBS January 23, 2009 local copy
Where America Stands: Stem Cell Research. CBS March 16, 2010 local copy
Potential Uses of Human Stem Cells •Spinal injuries and neuronal regeneration. •Skin cell replacement •Cardiovascular disease •Insulin producing pancreatic cells
You have had the science, but what are the ethical issues for hES or iPS cells? •consent & confidentiality of donors coded but anonymous •exploitation of young women •animal-human chimeras reaching adults integration of human genes into nonhuman animal tissues nonhuman primates of particular concern no animal with hES cells introduced should be allowed to breed •religious concerns •other ethical issues