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LIN28 is a Novel Molecular Player
Involved in Colorectal Cancer Development
Ho-Chou Tu, Ph.D
Laboratory of George Q. Daley
Boston Children’s Hospital/Harvard Medical School
Fight Colorectal Cancer Advocacy Workshop
03/16/2015
Genetics Changes During CRC Development
Kerr et al., Nature Reviews of Cancer (2003)
Wnt Signaling
Our Goals to Improve the Current Field
of CRC Research
1. Generate a late-stage CRC animal model
2. Identify and characterize novel molecular targets
for more specific therapeutic design
Viswanathan and Daley, Cell (2010)
Cancer Behaves Very Much Like Embryos
LIN28ALIN28B
Ziron Qian
Aberrant Expression of LIN28A and
LIN28B in Human Colorectal Cancer
Generation of Gut-Specific LIN28
Transgenic Animals
Induction of LIN28 Drives Tumors in
the Mouse Intestines
Human Colon Adenocarcinoma
http://en.wikipedia.org/
LIN28-driven Tumors are Adenocarcinoma
Resembling Human CRC
Lin28a
Tumors
LIN28B
Tumors
LIN28A/B Status Correlates with Invasive
Pathology in Human Colorectal Cancers
Ziron Qian
LIN28A/B Expression Predicts
Poorer Long Term Survival Rate
Ziron Qian
LIN28
Molecular mechanisms
Interacting pathways
In vivo platform for developing new therapeutics
LIN28: Novel Onco-proteins in
Colorectal Cancer Development
Acknowledgement
The Daley lab
-George
-Sarah Schwitalla
-Grace LaPier
-Alena Yermalovich
-Sam Ross
-Achia Urbach
-John Powers
-all Daley lab members
-Charlie Fuchs
-Shugi Ogino
-Ziron Qian
DFCI
Rodent Path Core
-Rod Bronson
-Gavin Meredith
-Jeffery Ku
-Shann-Ching Chen

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Call-on Congress Panel Discussion Part 3 Ho-Chou Tu #ConC2015

Hinweis der Redaktion

  1. In summary, I have created a novel colorectal cancer mouse model by overexpressing a novel oncoprotein found highly expressed in human CRCs. With this in vivo model in hand, I will set out to further dissect the moledular mechanisms down stream of Lin28, and also it’s interaction withesignaling pathways that’s known to play major roles in CRC development including Wntm Kras and p53….Lastly, we are also developing small molecules that targets Lin28/let-7 interaction, we hope to use this mouse model as a great pre-clinical in vivo platform for drug screen. CRC is the 2nd most cancers world wide, and so far, the best way to target it is still surgery plus conventional chemotherapy…I hope that by generating new animal models, we are able to model human CRC better and help designing more effective drugs