van Heel, David A
Mayo Clinic
Blizard Institute and Institute for Population Health Sciences, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Citations 3
Characterising a healthy adult with a rare HAO1 knockout to support a therapeutic strategy for primary hyperoxaluria
McGregor, Tracy L., Yee, Elaine, Mason, Dan , Nioi, Paul , Ticau, Simina , Pelosi, Marissa, Loken, Perry R , Finer, Sarah , Lawlor, Deborah A, Fauman, Eric B. , Huang, Qin Qin , Griffiths, Chris , MacArthur, Daniel G. , Oglesbee, Devin , Erbe, David V., Heel, David A. van , Lawlor, Debbie A. , Finer, Sarah , Lieske, John C , van Heel, David A , Oglesbee, Devin , MacArthur, Daniel G , Hunt, Karen A. , Trembath, Richard C. , Lieske, John C. , Wright, John
eLife | March 24, 2020 | Volume: 9 | Issue: No issue available | Pages: No page available
By sequencing autozygous human populations, we identified a healthy adult woman with lifelong complete knockout of HAO1 (expected ~1 in 30 million outbred people). HAO1 (glycolate oxidase) silencing is the mechanism of lumasiran, an investigational RNA interference therapeutic for primary hyperoxaluria type 1. Her plasma glycolate levels were 12 times, and urinary glycolate 6 times, the upper limit of normal observed in healthy reference individuals (n = 67). Plasma metabolomics and lipidomics (1871 biochemicals) revealed 18 markedly elevated biochemicals (>5 sd outliers versus n = 25 controls) suggesting additional HAO1 effects. Comparison with lumasiran preclinical and clinical trial data suggested she has <2% residual glycolate oxidase activity. Cell line p.Leu333SerfsTer4 expression showed markedly reduced HAO1 protein levels and cellular protein mis-localisation. In this woman, lifelong HAO1 knockout is safe and without clinical phenotype, de-risking a therapeutic approach and informing therapeutic mechanisms. Unlocking evidence from the diversity of human genetic variation can facilitate drug development.
Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases
Haycock, Philip , Burgess, Stephen , Nounu, Aayah , Zheng, Jie , Okoli, George N. , Wade, Kaitlin H. , Timpson, Nicholas J. , Evans, David M. , Willeit, Peter , Aviv, Abraham , Gaunt, Tom R. , Hemani, Gibran , Mangino, Massimo , Ellis, Hayley, Kurian, Kathreena M. , Pooley, Karen A. , Eeles, Rosalind A. , Lee, Jeffrey E. , Fang, Shenying , Chen, Wei V., Law, Matthew H. , Bowdler, Lisa, Iles, Mark M. , Worrall, Bradford B. , Markus, Hugh S. , Hung, Rayjean J., Amos, Chris, Thompson, Deborah J. , O’Mara, Tracy A. , Wolpin, Brian M. , Ámundadóttir, Laufey T. , Trichopoulou, Antonia , Onland‐Moret, N. Charlotte , Lund, Eiliv , Canzian, Federico , Severi, Gianluca , Overvad, Kim , Gunter, Marc J. , Tumino, Rosario , Svenson, Ulrika, Rij, André van, Baas, Annette F., Bown, Matthew J. , Samani, Nilesh J. , t’Hof, Femke N.G. van, Tromp, Gerard , Jones, Gregory T. , Kuivaniemi, Helena , Elmore, James R. , Johansson, Mattias , McKay, James , Scélo, Ghislaine , Carreras‐Torres, Robert , Gaborieau, Valérie , Brennan, Paul , Bracci, Paige M. , Olson, Sara H. , Gallinger, Steven , Li, Donghui , Petersen, Gloria M. , Han, Jiali , Abnet, Christian C. , Freedman, Neal D. , Aben, Katja K.H. , Kiemeney, Lambertus A. , Vermeulen, Sita H. , Walsh, Kyle M. , Wrensch, Margaret , Rice, Terri, Turnbull, Clare , Litchfield, Kevin , Paternoster, Lavinia , Standl, Marie , Mijatovic, Vladan, Sapkota, Yadav , Zondervan, Krina T. , Nyholt, Dale R. , Heel, David A. van , Arking, Dan E. , Ashar, Foram N., Sotoodehnia, Nona, Woo, Daniel , Comeau, Mary E. , Brown, W. Mark , Silverman, Edwin K. , Hokanson, John E. , Hui, Jennie , Thompson, Philip J. , Morrison, Alanna C. , Smith, Nicholas L. , Christiano, Angela M. , Petukhova, Lynn , Betz, Regina C. , Zhang, Xuejun, Zhu, Caihong, Langefeld, Carl D. , Thompson, Susan D. , Wang, Feijie , Fingerlin, Tasha E. , Rotter, Jerome I. , Cotch, Mary Frances , Jensen, Richard A., Munz, Matthias , Dommisch, Henrik , Schäefer, Arne S. , Ollila, Hanna M. , Hillary, Ryan P. , Zeng, Chenjie , Zheng, Wei , Shu, Xiao-Ou , Reis, André , Uebe, Steffen , Hüffmeier, Ulrike , Kawamura, Yoshiya, Otowa, Takeshi , Sasaki, Tsukasa, Dávila, Sonia , Siminovitch, Katherine A. , Bei, Jin‐Xin , Zeng, Yi‐Xin , Chen, Bowang , Franke, Andre, Fischer, Annegret, Ellinghaus, David , Flores, Carlos , Noth, Imre , Ma, Shwu‐Fan , Foo, Jia Nee , Liu, Jianjun , Cox, David G. , Delattre, Olivier , Mirabeau, Olivier , Skibola, Christine F., Tang, Clara Sze-Man , Garcia-Barceló, Mercè, Su, Wen-Hui , Chang, Yu‐Sun , Wade, Tracey , Lee, Chaeyoung , Kubo, Michiaki , Cha, Pei-Chieng , Nakamura, Yusuke, Levy, Daniel , Hunt, S. E., Spector, Tim D. , Soranzo, Nicole , Barr, R. Graham, Kahali, Bratati , Speliotes, Elizabeth K. , Yerges-Armstrong, Laura M. , Cheng, Ching‐Yu , Wong, Tien Yin , Fogh, Isabella , Powell, John , Rice, Kenneth , Relton, Caroline L. , Martin, Richard M. , Smith, George Davey , Hung, Rayjean J. , Bowden, Jack , Yang, Qiong , Spurdle, Amanda B. , Stolzenberg‐Solomon, Rachael Z. , Duell, Eric J. , Neale, Rachel Ε. , Risch, Harvey A. , Klein, Alison P. , Taylor, Philip R. , Maris, John M. , Wiencke, John K. , Abecasis, Gonçalo R. , SanGiovanni, John Paul , Li, Yong , Low, Siew‐Kee , Montgomery, Grant W. , Hunt, Karen A. , Rosand, Jonathan M. , Cho, Michael H. , Ferreira, Manuel A. R. , Felix, Janine F. , Fan, Xing Hua , Xu, Lin , Schwartz, David A. , Han, Fang , Albagha, Omar , Ralston, Stuart H. , Sasaki, Tsukasa, Hibberd, Martin Lloyd , Xie, Gang , Försti, Asta , Landi, Stefano , Ellinghaus, David , Kim, Jong‐Won , Chang, Kai‐Ping , Martin, Nicholas G. , Gordon, Scott D. , Kimura, Masayuki , Hwang, Shih‐Jen , Manichaikul, Ani , Barr, R. Graham, Jonas, Jost B , Lin, Kuang , Amundadottir, Laufey , Kiemeney, Lambertus A , Eeles, Rosalind A , van Heel, David A , Gunter, Marc J , Canzian, Federico , Hung, Rayjean J , O'Mara, Tracy A , Abnet, Christian C , Haycock, Philip , Tumino, Rosario , Han, Jiali , Martin, Richard M , Severi, Gianluca , Reis, André , Zheng, Wei , Rotter, Jerome I , Carreras-Torres, Robert , Law, Matthew H , Davey Smith, George , Johansson, Mattias , Iles, Mark M , Morrison, Alanna C , Rice, Ken , Freedman, Neal D , Foo, Jia Nee , Levy, Daniel , Rice, Kenneth , Sapkota, Yadav , Wong, Tien Y , Liu, Jing
JAMA Oncology | February 27, 2017 | Volume: 3 | Issue: 5 | Pages: 636
Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology
Bai, Julio C. , Biagi, Federico , Card, Tim , Ciacci, Carolina , Ciclitira, Paul J. , Green, Peter H.R. , Hadjivassiliou, Marios , Holdoway, Anne , Heel, David A. van , Kaukinen, Katri , Leffler, Daniel A. , Leonard, Jonathan N., McGough, Norma, Davidson, Mike, Swift, G L, Walker, Marjorie M. , Zingone, Fabiana , Sanders, David S. , Group, Authors of the BSG Coeliac Disease Guidelines Development, Ludvigsson, Jonas F. , Lundin, Knut E. A. , Murray, Joseph A. , Group, Authors of the BSG Coeliac Disease Guidelines Development, van Heel, David A , Ciacci, Carolina
Gut | June 11, 2014 | Volume: 63 | Issue: 8 | Pages: 1210-1228
A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.