1 / 11

Kick it up a Notch

Kick it up a Notch. The Role of Notch Signaling in T Cell Differentiation and Cancer Ryan Zimmerman. Notch Signaling Acts in Many Cell Fate Choices. Notch knockout mice die before 10.5 days in gestation Cell death and patterning errors in lots of tissues.

alexandra-romero
Download Presentation

Kick it up a Notch

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Kick it up a Notch The Role of Notch Signaling in T Cell Differentiation and Cancer Ryan Zimmerman

  2. Notch Signaling Acts in Many Cell Fate Choices • Notch knockout mice die before 10.5 days in gestation • Cell death and patterning errors in lots of tissues Wild-type Notch pathway disrupted http://www0.gsf.de/ieg/groups/genome/delta_notch.html

  3. Immune System Overview • Specific and non-specific protection from bacteria, viruses and parasites. • All immune cells begin in the bone marrow. • Common precursors differentiate into two main types of cells: CD4+ CD8+ http://www.niaid.nih.gov/final/immun/immun.htm

  4. Notch’s Niche Binary cell-fate decisions in immune system precursor cells MacDonald et al. (2001) Notch1 and T-cell Development: insights from conditional knockout mice. Trends in Immunology. 22:155-160.

  5. Notch Signaling in T/B Cell Lineage Decision Presenilin MacDonald et al. (2001) Notch1 and T-cell Development: insights from conditional knockout mice. Trends in Immunology. 22:155-160.

  6. Disruption of Notch Signaling Leads to Cancers • Leukemia: excessive proliferation and incorrect development of leukocytes Acute promyelocytic leukemia (peripheral blood smear, Wright's stain). http://www.dorlands.com/def.jsp?id=12485436

  7. Disruption of Notch Signaling is Involved in a Specific Leukemia • T cell Acute Lymphoblastic Leukemia (T-ALL) • T-cell: display pre-T or T antigens • Acute: sudden onset • Lymphoblastic: involves immature T or B cells not macrophages, etc. • 1,450 of the 23,300 leukemia deaths in 2004 were from ALL http://www.dorlands.com/def.jsp?id=12485436, http://www.leukemia-lymphoma.org/all_page?item_id=9346#_deaths

  8. Genetics of T-ALL Screpanti et al. (2003). Notch: a unifying target in T-cell acute lymphoblastic leukemia? Trends in Molecular Medicine. Vol. 9: 30-35.

  9. Notch3 is Overexpressed in T-ALL T cell leukemiasNon-T cell leukemias Bellavia et al. (2002). Combined expression of pT and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. PNAS. Vol. 99. 6: 3788-3793.

  10. Notch Signaling Components Are Therapeutic Targets Presenilin Inhibitors Induce Apoptosis in T-ALL Lines Weng et al. (2003). Growth Surpression of Pre-T Acute Lymphoblastic Leukemia Cells by Inhibition of Notch Signaling. Molecular and Cell Biology. Vol. 23. 2: 655-664.

  11. Summary • Notch signaling is involved in many types of cell fate decisions • Critical for T cell differentiation • 2 binary decisions • Misregulation is associated with T-ALL • Notch3 overexpression • T-ALL is responsive to therapies that target elements of the Notch pathway • Presenilin inhibitors

More Related