Genetic susceptibility to cryptococcal meningitis

In a collaborative study with Dr Tihana Bicanic (Institute of Infection & Immunity), we performed the first genome-wide association study (GWAS) for susceptibility to cryptococcal meningitis identifying the CSF1 gene locus, providing valuable new insights into the host-pathogen response, which was recently published in Open Forum Infectious Diseases. The next phase of this work is continuing by analysing RNAseq data from peripheral blood mononuclear cells treated with antigens, to map out the relevant immune response pathways.

Genomics of neuromuscular disease

In a study with Dr Yalda Jamshidi (Genetics) and Dr Daniel Osborn (Genetics) through collaboration with various centers in Iran we have recruited several hundred patients with neuromuscular diseases, and with a grant from Muscular Dystrophy UK (I am co-applicant), we have performed whole-exome sequencing in order to identify novel genetic causes of disease. We have recently published a paper in Molecular Genetics & Genomic Medicine, identifying novel disease-causing copy-number variants in LAMA2.

Genetic architecture of Lipoedema

In a collaborative study with Prof Pia Ostergaard (Genetics), I have supervised a GWAS of Lipoedema in which we have identified novel fat metabolism loci. To continue this work we have been funded by the Lipoedema Foundation.

Genomics of sudden cardiac death

In a collaborative study with Prof Elijah Behr (Cardiology), we have completed a study in the 100,000 Genomes Project on the diagnostic utility of whole genome sequencing in sudden unexplained death. This work is continuing thanks to large collaborative award from the BHF on which I am co-applicant to perform whole genome sequencing and identify new disease-causing genes in over one thousand cases.

Selected Publications

Gray B, Baruteau A E, Antolin A A, Pittman A, Sarganas G, Molokhia M, Blom M T, Bastiaenen R, Bardai A, Priori S G, Napolitano C, Weeke P E, Shakir S A, Haverkamp W, Mestres J, Winkel B, Witney A A, Chis-Ster I, Sangaralingam A, Camm A J, … Behr E R (2022) Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome. Circulation Genomic and precision medicine CIRCGEN121003391. Advance online publication https://doiorg/101161/CIRCGEN121003391

Riachi M, Polubothu S, Stadnik P, Connor H, Barberan Martin S, Charman C R, Cheng I L, Gholam K, Ogunbiyi O, Paige D G, Sebire N J, Pittman A, Di W L, & Kinsler V A (2021). Molecular genetic dissection of inflammatory linear verrucous epidermal naevus leads to successful targeted therapy. The Journal of investigative dermatology, S0022-202X(21)01320-8. Advance online publication. https://doi.org/10.1016/j.jid.2021.02.765

Simone R, Javad F, Emmett W, Wilkins O G, Almeida F L, Barahona-Torres N, Zareba-Paslawska J, Ehteramyan M, Zuccotti P, Modelska A, Siva K, Virdi G S, Mitchell J S, Harley J, Kay V A, Hondhamuni G, Trabzuni D, Ryten M, Wray S, Preza E, … Pittman A… de Silva R (2021) MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration Nature ,94(7861) 117–123 

Olivia V. Poole*, David Murphy*, Chiara Pizzamiglio, Jana Vandrocova, Cathy E. Woodward BSc, Robyn Labrum, Micol Falabella, William L. Macken, Enrico Bugiardini , Anthony A. Amato, Susan J. Hayflick, Queen Square Genomics, Hallgeir Jonvik , Nicholas Wood, Henry Houlden, Michael G. Hanna, Alan Pittman*, Robert D.S. Pitceathly* (2021). Mitochondrial DNA analysis from exome sequencing data improves the diagnostic yield in neurological diseases. Annals of Neurology. doi: 10.1002/ana.26063 https://onlinelibrary.wiley.com/doi/10.1002/ana.26063?af=R

Cauley ES, Pittman A, Mummidivarpu S, Karimiani EG, Martinez S, Moroni I, Boostani R, Podini D, Mora M, Jamshidi Y, Hoffman EP, Manzini MC. (2020). Novel mutation identification and copy number variant detection via exome sequencing in congenital muscular dystrophy. Mol Genet Genomic Med, 8(11), e1387. doi:10.1002/mgg3.1387.

Pittman AM, Naranjo S, Jalava SE, Twiss P, Ma Y, Olver B, Lloyd A, Vijayakrishnan J, Qureshi M, Broderick P, van Wezel T, Morreau H, Tuupanen S, Aaltonen LA, Alonso ME, Manzanares M, Gavilán A, Visakorpi T, Gómez-Skarmeta JL, Houlston RS (2010). Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H. PLoS Genet, 6(9), e1001126. doi:10.1371/journal.pgen.1001126.

Kannambath S, Jarvis JN, Wake RM, Longley N, Loyse A, Matzaraki V, Aguirre-Gamboa R, Wijmenga C, Doyle R, Paximadis M, Tiemessen CT, Kumar V, Pittman A, Meintjes G, Harrison TS, Netea MG, Bicanic T. (2020). Genome-Wide Association Study Identifies Novel Colony Stimulating Factor 1 Locus Conferring Susceptibility to Cryptococcosis in Human Immunodeficiency Virus-Infected South Africans. Open Forum Infect Dis, 7(11), ofaa489. doi:10.1093/ofid/ofaa489.

Pittman AM, Naranjo S, Webb E, Broderick P, Lips EH, van Wezel T, Morreau H, Sullivan K, Fielding S, Twiss P, Vijayakrishnan J, Casares F, Qureshi M, Gómez-Skarmeta JL, Houlston RS. (2009). The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression. Genome Res, 19(6), 987-993. doi:10.1101/gr.092668.109.

COGENT Study, Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, Lubbe S, Chandler I, Vijayakrishnan J, Sullivan K, Penegar S, Colorectal Cancer Association Study Consortium, Carvajal-Carmona L, Howarth K, Jaeger E, Spain SL, Walther A, Barclay E, Martin L, Gorman M, Domingo E, Teixeira AS, CoRGI Consortium, Kerr D, Cazier J-B, Niittymäki I, Tuupanen S, Karhu A, Aaltonen LA, Tomlinson IPM, Farrington SM, Tenesa A, Prendergast JGD, Barnetson RA, Cetnarskyj R, Porteous ME, Pharoah PDP, Koessler T, Hampe J, Buch S, Schafmayer C, Tepel J, Schreiber S, Völzke H, Chang-Claude J, Hoffmeister M, Brenner H, Zanke BW, Montpetit A, Hudson TJ, Gallinger S, Campbell H, Dunlop MG. (2008). Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat Genet, 40(12), 1426-1435. doi:10.1038/ng.262.

Broderick P, Carvajal-Carmona L, Pittman AM*, Webb E, Howarth K, Rowan A, Lubbe S, Spain S, Sullivan K, Fielding S, Jaeger E, Vijayakrishnan J, Kemp Z, Gorman M, Chandler I, Papaemmanuil E, Penegar S, Wood W, Sellick G, Qureshi M, Teixeira A, Domingo E, Barclay E, Martin L, Sieber O, CORGI Consortium, Kerr D, Gray R, Peto J, Cazier J-B, Tomlinson I, Houlston RS. (2007). A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nat Genet, 39(11), 1315-1317. doi:10.1038/ng.2007.18.

Shaw-Smith C, Pittman AM*, Willatt L, Martin H, Rickman L, Gribble S, Curley R, Cumming S, Dunn C, Kalaitzopoulos D, Porter K, Prigmore E, Krepischi-Santos ACV, Varela MC, Koiffmann CP, Lees AJ, Rosenberg C, Firth HV, de Silva R, Carter NP. (2006). Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Nat Genet, 38(9), 1032-1037. doi:10.1038/ng1858.

Pittman AM, Myers AJ, Duckworth J, Bryden L, Hanson M, Abou-Sleiman P, Wood NW, Hardy J, Lees A, de Silva R. (2004). The structure of the tau haplotype in controls and in progressive supranuclear palsy. Hum Mol Genet, 13(12), 1267-1274. doi:10.1093/hmg/ddh138.

Lead Investigator Lipedema foundation (March 2021) with Prof Pia Ostergaard and Kristina Gordon for £176,797; "Genetic architecture of Lipedema".

Co-investigator on 4 funded grants with a total income of £1.496M from the BHF, St Georges Hospital Charity and Muscular Dystrophy UK.

Prof Veronica Kinsler (UCL Institute of Child Health and Crick Institute, London), Paediatric Dermatology and Dermatogenetics. “Optimising detection of low-level mosaic variants”.

Prof Perry Elliot and Dr Petros Syrris (UCL Institute of Cardiovascular Sciences, London). “Genomics of cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy”.

Prof Kate Tatton-Brown, Dr Kate Everett, and Dr Chris Carroll. “Clinical and molecular evaluation of overgrowth and intellectual disability syndromes” (OGID). In this project I am the workstream lead on the genomic analysis.

Sahar Mansour and Meriel McEntagart – mining Genomics England project data to solve rare disease cases.

I am a Fellow of the Higher Education Academy.

I contribute lectures and workshops in my areas of expertise to the BSc Biomedical Sciences (BMS), MSc Genomic Medicine, MSc/MRes Translational Medicine, MSc Sports Cardiology and the St George’s University of London (SGUL) Summer School.

Co-lead for the MSc Genomic Medicine module “Genomics of common and rare inherited diseases"

Lead for the MSc/MRes Translational Medicine module “Genomic Technologies for Clinical Diagnostics"