ashakru Goto Github PK

Computational Haematology and Genomics

Topography of DLBCL genetic landscape.
Coloured hills depict known genetic subtypes.
Whilst patients positioned on top of the coloured
“hills” will bereproducibly classified by each
classification system, patients positioned in the
“valleys” may be unclassified or classified
alternatively across different classification systems.
Hills without colour correspond to unknown DLBCL
subtypes which may emerge in the future from currently
unclassified cases.

I am first and foremost a computational clinician. I look at medicine through big data, thinking about patients I can help in the future. I am focusing on studying cancer genomics with special interest in protein translation. My ambition is to drive change in how we diagnose and treat haematological malignancies. This is a team effort, therefore I am a committed advocate for open science. I believe that transparency, collaboration, and accessibility serve as catalysts for accelerated progress in science.

Currently, I am a postdoctoral researcher in Dr Daniel Hodson’s lab at the University of Cambridge. I am also participating in the EHA-EMBL/EBI Computational Biology Training in Hematology, run by the European Haematology Association a year-long programme for early-career researchers interested in computational haematology.

The DIRECT Trial is a prospective molecular profiling trial of patients undergoing first-line therapy for DLBCL. We are developing a customised capture panel and analytical pipeline AULE (Automated Ultrasensitive Lymphoma Evaluation) for ultrasensitive assessment of ctDNA in patients with DLBCL. Our mission is to make liquid biopsy diagnostics avaliable for NHS patients.

Review: Genetic Profiling in Diffuse Large B-Cell Lymphoma: The Promise and the Challenge

The human genome is believed to encompass around 20,000 protein-coding sequences. However, recent advancements in sequencing technologies, like Ribo-Seq, have opened up exciting possibilities for re-evaluating the landscape of translated Open Reading Frames (ORFs). This project aims to undertake a comprehensive examination of non-canonical ORFs in B-cells. There is potential for this project to reveal an entire new level of regulation in B cell malignancy and immunity.

In development: BilbORF, an open science project on performing differential ORF usage analysis

The maintenance of protein synthesis and folding homeostasis is critical for cellular survival. When the rate of protein production surpasses the cellular capacity for protein folding, apoptosis is initiated. The MYC oncogene boost protein translation, which becomes toxic to cells when deregulated. MYC deregulation is a hallmark of Burkitt's Lymphoma, one of the most aggressive forms of cancer in humans. Our findings revealed that the loss of DDX3X, an RNA helicase, mitigates the proteotoxic stress induced by oncogenic MYC. Additionally, we have suggested a potential mechanism for the observed male bias in Burkitt's Lymphoma.

Paper: Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis
Editorial: Sex, life, and death in MYC-driven lymphomagenesis