I have been conducting human genomics research for over 20 years. The highlights of my career are the discovery of the polymorphic Sp1 site in the COL1A1 gene and its association with osteoporosis, the identification of variation in the TCF7L2 gene playing a key role in conferring type 2 diabetes risk and providing leadership in an international genetics effort to characterize genes influencing birth weight and common childhood obesity risk. I have also previously played a role in uncovering genes involved in other traits, including cleft lip with or without palate, scoliosis, inflammatory bowel disease, autism, ADHD, head circumference, intracranial volume, myocardial infarction, pediatric eosinophilic esophagitis, type 1 diabetes, asthma, multiple sclerosis and neuroblastoma.
As a Director of the Center for Spatial and Functional Genomics at the Children's Hospital of Philadelphia, my current work primarily involves investigating disease genomics with a specific focus on pediatrics. Utilizing high-throughput genotyping and sequencing technologies, combined with statistical and bioinformatic approaches, my goals include unraveling genomic puzzles related to childhood obesity, pediatric bone strength determination, early onset diabetes and cancer. These phenotypes are known to be strongly determined by genetic factors; however, resolving genomic contributors to such complex phenotypes in adults has been impeded by interaction with strong environmental factors. Distillation of the genomic architecture in these complex traits should be easier to determine in children, where the relatively short period of their lifetime limits the impact of environmental exposure. Given the global prevalence of such diseases, prevention of these disorders and their serious complications must be addressed in order to reduce individual morbidity and the economic burden on society.
Funding as PI/MPI:
R01 HD056465, R01 AG057516, R01 HD100406, R01 DK122586, R01 HL143790, R01 AG072705, UM1 DK126194, Daniel B. Burke Endowed Chair for Diabetes Research
(Completed: R01 DK085212, R21 HD089824, R01 HD058886)
Funding as Co-investigator:
R01 AI154773, R01 AI146026, R01 AR056837, R01 AR069055, R01 AR076241, R01 DK097830, R01 DK056268, R01 EY023557
Jonathan P. Bradfield, Elizabeth A. Burton, Mitchell Conery, Kieona Cook, Max Dudek, Mary Ann Hazuga, Sheridan H. Littleton, Matthew C. Pahl, James A. Pippin, Shilpa Sonti, Khanh B. Trang, Nicholas A. Wachowski, Amber J. Zimmerman
Former members: Mariana Argenziano, Keith Boehm, Alessandra Chesi, K. Sonal R. Choudhary, Diana L. Cousminer, Sandra Deliard, Matthew E. Johnson, Vanessa C. Guy, Reza K. Hammond, Kenyaita M. Hodge, Brian T. Johnston, Chiara Lasconi, Michelle E. Leonard, Sumei Lu, Elisabetta Manduchi, Rajashree Mishra, Ursula W. Parlin, Chun Su, Qianghua Xia, Jianhua Zhao
J. Palermo*, A. Chesi*, A. Zimmerman*, S. Sonti, M.C. Pahl, C. Lasconi, E.B. Brown, J.A. Pippin, A.D. Wells, F. Doldur-Balli, D. Mazzotti, A.I. Pack, P.R. Gehrman*, S.F.A. Grant* and A.C. Keene*: Variant-to-gene mapping followed by cross-species genetic screening identifies GPI-anchor biosynthesis as a regulator of sleep. Science Advances 9: eabq0844, 2023 Notes: *equal contribution.
C. Lasconi*, M.C. Pahl*, J.A. Pippin, C. Su, M.E. Johnson, A. Chesi, K. Boehm, E. Manduchi, K. Ou, M.L. Golson, A.D. Wells, K.H. Kaestner and S.F.A. Grant: Variant-to-gene-mapping analyses reveal a role for pancreatic islet cells in conferring genetic susceptibility to sleep-related traits. Sleep 45: zsac109, 2022 Notes: *equal contribution.
C. Su, L. Gao, C.L. May, J.A. Pippin, K. Boehm, M. Lee, C. Liu, M.C. Pahl, M.L. Golson, A. Naji, The Human Pancreas Analysis Consortium, S.F.A. Grant*, A.D. Wells* and K.H. Kaestner*: The three-dimensional chromatin structure of the major human pancreatic cell types reveals lineage-specific regulatory architecture of T2D risk. Cell Metabolism 34: 1394–1409, 2022 Notes: *equal contribution.
M.C. Pahl, C. Le Coz, C. Su, P. Sharma, R.M. Thomas, J.A. Pippin, E.C. Cabrera, M.E. Johnson, M.E. Leonard, S. Lu, A. Chesi, K.E. Sullivan, N. Romberg, S.F.A. Grant* and A.D. Wells*: Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types. Genome Biology 23: 125, 2022 Notes: *equal contribution.
D.L. Cousminer*, Y. Wagley*, J.A. Pippin*, A. Elhakeem, G.P. Way, M.C. Pahl, S.E. McCormack, A. Chesi, J.A. Mitchell, J.M. Kindler, D. Baird, A. Hartley, L. Howe, H.J. Kalkwarf, J.M. Lappe, S. Lu, M.E. Leonard, M.E. Johnson, H. Hakonarson, V. Gilsanz, J.A. Shepherd, S.E. Oberfield, C.S. Greene, A. Kelly, D.A. Lawlor, B.F. Voight, A.D. Wells, B.S. Zemel, K. Hankenson* and S.F.A. Grant*: Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual through variant-to-gene mapping. Genome Biology 22: 1, 2021 Notes: *equal contribution.
M.C. Pahl*, C.A. Doege*, K.M. Hodge*, S.H. Littleton*, M.E. Leonard, S. Lu, R. Rausch, J.A. Pippin, M. Caterina De Rosa, A. Basak, J.P. Bradfield, R.K. Hammond, K. Boehm, R.I. Berkowitz, C. Lasconi, C. Su, A. Chesi, M.E. Johnson, A.D. Wells, B.F. Voight, R.L. Leibel, D.L. Cousminer* and S.F.A. Grant*: Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant common complex traits. Nature Communications 12: 6749, 2021 Notes: *equal contribution.
D.L. Cousminer and S.F.A. Grant: Public resources aid diabetes gene discovery. Nature Genetics 50: 1499-1500, 2018.
J.P. Bradfield*, H.R. Taal*, N.J Timpson, A. Scherag, C. Lecoeur, N.M. Warrington, E. Hypponen, C. Holst, B. Valcarcel, E. Thiering, R.M. Salem, F.R. Schumacher, D.L. Cousminer, P.M.A. Sleiman, J. Zhao, R.I. Berkowitz, K.S. Vimaleswaran, I. Jarick, C.E. Pennell, D.M. Evans, B. St Pourcain, D.J. Berry, D.O. Mook-Kanamori, A. Hofman, F. Rivadeneira, A.G. Uitterlinden, C.M. van Duijn, R.J.P. van der Valk, J.C. de Jongste, D.S. Postma, D.I. Boomsma, W.J. Gauderman, M.T. Hassanein, C.M. Lindgren, R. Mägi, C.A.G. Boreham, C.E. Neville, L.A. Moreno, P. Elliott, A. Pouta, A.L. Hartikainen, M. Li, O. Raitakari, T. Lehtimäki, J.G Eriksson, A. Palotie, J. Dallongeville, S. Das, P. Deloukas, G. McMahon, S.M. Ring, J.P. Kemp, J.L. Buxton, A.I.F. Blakemore, M. Bustamante, M. Guxens, J.N. Hirschhorn, M.W. Gillman, E. Kreiner-Møller, H. Bisgaard, F.D. Gilliland, J. Heinrich, E. Wheeler, I. Barroso, S. O’Rahilly, A. Meirhaeghe, T.I.A. Sørensen, C. Power, L.J. Palmer, A. Hinney, E. Widen, I.S. Farooqi, M.I. McCarthy, P. Froguel, D. Meyre, J. Hebebrand, M.R. Jarvelin, V.W.V. Jaddoe, G. Davey Smith, H. Hakonarson and S.F.A. Grant for the Early Growth Genetics (EGG) Consortium: A genome-wide association meta-analysis identifies new childhood obesity loci. Nature Genetics 44: 526–531, 2012 Notes: *equal contribution.
H. Hakonarson*, S.F.A. Grant*, J.P. Bradfield*, L. Marchand, C.E. Kim, J.T. Glessner, R. Grabs, T. Casalunovo, S.P. Taback, E.C. Frackelton, M.L. Lawson, L.J. Robinson, R. Skraban, Y. Lu, R.M. Chiavacci, C.A. Stanley, S.E. Kirsch, E.F. Rappaport, J.S. Orange, D.S. Monos, M. Devoto, H. Qu and C. Polychronakos: A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 448: 591-4, 2007 Notes: *equal contribution.
S.F.A. Grant, G. Thorleifsson, I. Reynisdottir, R. Benediktsson, A. Manolescu, J. Sainz, A. Helgason, H. Stefansson, V. Emilsson, A. Helgadottir, U. Styrkarsdottir, K.P. Magnusson, G. B. Walters, E. Palsdottir, T. Jonsdottir, T. Gudmundsdottir, A. Gylfason, J. Saemundsdottir, R.L. Wilensky, M.P. Reilly, D.J. Rader, Y. Bagger, C. Christiansen, V.Gudnason, G. Sigurdsson, U. Thorsteinsdottir, J.R. Gulcher, A. Kong and K. Stefansson : Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nature Genetics 38: 320-3, 2006 Notes: TOP COVER STORY.
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Last updated: 02/01/2023
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