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

LIN

28A

LIN

28B

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

LIN28BTumors

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