Marco Herold-Projects

Marco Herold-Projects


Elucidating the role of the pro-survival protein A1 in cancer

The pro-survival Bcl-2 family member A1 (the human counterpart is called BFL1) has been implicated in diverse cancers, including various leukaemias as well as lymphomas and melanoma. We have developed a conditional A1 knockout model and CRISPR approaches to delete A1/BFL-1 in cell lines.

Recent results suggest that A1 might represent a resistance factor in patients with diverse haematological cancers, which have been treated with current BH3 mimetic drugs targeting MCL-1 or BCL-2. Therefore, we are currently developing models of resistance to evaluate the role of A1 and the potential of targeting this pro-survival BCL-2 protein. 

Team members: Dr Lahiru Gangoda, Dr Margs Brennan

Identification of novel tumour suppressor genes and oncogenes by CRISPR/Cas9 library screens in vivo

Human cancers are driven by activating or inactivating mutations in oncogenes and tumour suppressor genes.

To identify tumour-driving aberrations we are deleting, activating or specifically mutating genes by using diverse new CRISPR tools we have developed in our lab in vivo. These experiments will reveal genes critical for the growth of tumour cells, thereby representing new targets for cancer therapy.  

Within this project we are also developing latest CRISPR tools, such as transcriptional activator and base editing platforms for in vivo usage.

Additionally, we are also implementing CRISPR as a diagnostic tool for detection of infectious disease and cancer.  

Project resourceOur cancer-preventing genes revealed

Team members: Yexuan Deng, Maggie Potts, Dr Martin Pal, Dr Andrew Kueh

Role of the epigenetic regulator DNMT3a in haematopoietic cancers

Mutations in the epigenetic regulator DNMT3a have been reported in a wide range of haematological cancers.

We have developed a pre-clinical model which harbours the most common mutation found in DNMT3a in acute myeloid leukaemia (AML).

Our studies aim to clarify the role of mutant DNMT3a in these models and to find new treatment regimens associated with mutant DNMT3a.     
Team members: Erin Lawrence, Dr Andrew Kueh

Haematopoietic stem cell regulation by the E3 ubiquitin ligase HectD1

We identified HectD1 as an essential gene for haematopoietic stem cell function. To understand its exact role in HSC function, we have developed novel in vivo models suggesting a regulation of inflammation by HectD1.

Additionally, we aim to identify the exact molecular mechanism underlying the deregulation induced by HectD1. Our collaborations with the Ubiquitin Division will help clarify these mechanisms.

Team member: Dr Margs Brennan