Human Adrenal and Reproductive Biology
Our aims are to better understand the genetic mechanisms of human endocrine development with a focus on adrenal and reproductive biology, cell growth and sex chromosomes. This work is leading to improved diagnosis and management.
Projects
Our current work focusses on the role of somatic and genomic variation on human reproductive development, growth and endocrine function.
1) Sex-differences and sex-chromosomes in development
We are interested in the dynamic genetic/transcriptomic events underlying development of the gonads (testes, ovaries) and adrenal glands in human. We are now studying the interaction of genes, sex chromosomes and hormones in early development.
2) Molecular basis of endocrine disorders
We are continuing our efforts to find new genetic causes and mechanisms for adrenal and reproductive dysfunction, fetal growth restriction and pregnancy complications. This knowledge is leading to personalised approaches to management and the potential discovery of new therapeutic approaches for a range of conditions.
3) Early-Onset primary ovarian insufficiency (POI)
We are studying the genetic causes of early-onset POI and linking our findings to early human ovary development and meiosis.
Key publications
Del Valle, I., Young, M.D., Kildisiute, G. et al. An integrated single-cell analysis of human adrenal cortex development. JCI Insight. 2023;8:e168177. doi: 10.1172/jci.insight.168177.
McGlacken-Byrne, S. M., del Valle, I., Stabej, P. L. Q., et al. Pathogenic variants in the human m(6)A reader YTHDC2 are associated with primary ovarian insufficiency. JCI Insight, 2022:7, e154671. doi:10.1172/jci.insight.154671
Buonocore, F., Maharaj, A., Qamar, Y., et al. Genetic analysis of pediatric primary adrenal insufficiency of unknown etiology: 25 years’ experience in the UK. Journal of the Endocrine Society. 2021;5:bvab08
Buonocore, F., Kühnen, P., Suntharalingham, J. P., et al. Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans. J Clin Invest. 2017;127(5):1700-1713. PMCID:5409795
Del Valle, I., Buonocore, F., Duncan, A. J., et al. A genomic atlas of human adrenal and gonad development. Wellcome Open Res. 2017:2:25. PMCID:5407452
Guran, T., Buonocore, F., Saka, N., et al. Rare causes of primary adrenal insufficiency: Genetic and clinical characterization of a large nationwide cohort. J Clin Endocrinol Metab. 2016;101(1):284-292. PMCID:4701852
Arboleda, V. A., Lee, H., Parnaik, R., et al. Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nat Genet. 2012;44(7):788-792. PMCID:3386373
Lourenço, D., Brauner, R., Lin, L., et al. Mutations in NR5A1 associated with ovarian insufficiency. N Engl J Med. 2009;360(12):1200-1210. PMCID:2778147
Achermann, J. C., Ito, M., Ito, M.,et al. A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet. 1999;22:125-126.