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HOXA9 degradome SIGNED

Deciphering the machinery involved in stability of the transcription factor HOXA9.

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 HOXA9 degradome project word cloud

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Project "HOXA9 degradome" data sheet

The following table provides information about the project.

Coordinator
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG 

Organization address
address: IM NEUENHEIMER FELD 280
city: HEIDELBERG
postcode: 69120
website: www.dkfz.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website https://ebertlab.dana-farber.org/
 Total cost 239˙860 €
 EC max contribution 239˙860 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-GF
 Starting year 2016
 Duration (year-month-day) from 2016-11-07   to  2019-11-06

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG DE (HEIDELBERG) coordinator 239˙860.00
2    THE BRIGHAM AND WOMEN'S HOSPITAL INC US (BOSTON MA) partner 0.00

Map

 Project objective

Transcription factors are often mutated or aberrantly expressed in cancer and drive carcinogenesis. HOXA9 is a master transcription factor that controls a network of genes critical for hematopoiesis. It shows increased expression levels in more than 50% of patients with acute myeloid leukemia (AML), and is strongly associated with poor clinical outcome. Since the initiation and progression of AML depend on elevated HOXA9 levels, it represents an attractive therapeutic target to combat this aggressive malignancy. However, transcription factors are often not amenable to direct pharmacologic inhibition. To overcome this limitation, an alternative strategy aiming at interference with the transcription factor-specific 'degradome' - the degradation machinery regulates HOXA9 stability. To this end, we aim to elucidate the HOXA9 degradome with the goal of identifying its druggable nodes. Specifically, we plan to (1) identify regulatory proteins involved in the degradation of HOXA9 by performing a FACS-based positive selection screen with a focused CRISPR/Cas9 library as perturbation tool, (2) validate candidate proteins involved in the control of HOXA9 stability, and (3) characterize hits suitable for pharmacologic targeting. For the most promising HOXA9 regulators, we will determine their specificity by assessing global changes of protein abundance by proteomics. The potential of employing hits for pharmaceutical targeting will be evaluated by integrating molecular information with clinical data. In summary, this project aims to establish novel strategies for the dissection of the transcription factor HOXA9 degradome by developing a flexible screening platform. Through this project, I will not only acquire new skills but also establish a scientific network, which is expected to intensify the collaboration between DKFZ and Harvard Medical School. Two years’ experience in USA followed by one year in Heidelberg will be undoubtedly a milestone in my career development.

 Publications

year authors and title journal last update
List of publications.
2018 Quinlan L. Sievers, Georg Petzold, Richard D. Bunker, Aline Renneville, Mikołaj Słabicki, Brian J. Liddicoat, Wassim Abdulrahman, Tarjei Mikkelsen, Benjamin L. Ebert, Nicolas H. Thomä
Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN
published pages: eaat0572, ISSN: 0036-8075, DOI: 10.1126/science.aat0572
Science 362/6414 2019-02-11

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