I perform translational research for patients with rare diseases, testing functional consequences of the patient’s mutations to determine whether they cause the disease. Some of these tests involve CRISPR/Cas9 gene editing to insert a genetic change into cell lines, which are then assayed to see whether the activity of the gene is altered due to the mutation. Currently, together with collaborators within WTCHG and at the WIMM, we are testing the effect of different mutations on a gene that causes a rare form of epilepsy. We are also working together with a group in the Biochemistry department to find out whether an alteration in RNA binding is involved in a developmental syndrome. Determining the genetic causes of rare diseases can help in treatment decisions, may discover novel pathways involved in the disorder, and could contribute to identifying new/re-purposed medicines for improved treatment of patients.
Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases.
Pagnamenta AT. et al, (2023), Genome medicine, 15
The clinical relevance of tumor RAS/TP53 dual mutation in early and metastatic colorectal cancer (CRC).
Seligmann JF. et al, (2022), JOURNAL OF CLINICAL ONCOLOGY, 40
Identification of Circulating Genomic and Metabolic Biomarkers in Intrahepatic Cholangiocarcinoma
Winter H. et al, (2019), Cancers, 11, 1895 - 1895
Conserved properties of genetic architecture of renal and fat transcriptomes in rat models of insulin resistance.
Otto GW. et al, (2019), Disease models & mechanisms, 12
Delineation of dominant and recessive forms of
‐associated Noonan syndrome
Pagnamenta AT. et al, (2019), Clinical Genetics, 95, 693 - 703