F. Sessions Cole, MD

Park J. White Professor
Newborn Medicine
Cell Biology and Physiology

Human and Statistical Genetics Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-454-6183

  • 314-286-2866

  • 314-454-4633

  • MSC 8208-16-1

  • 5th floor, 4444 Forest Park Parkway

  • fcole@wustl.edu

  • https://wambachcolelab.wustl.edu/

  • functional genomics, bioinformatics, pulmonary surfactant, lung development

  • Genetic lung disease, Surfactant protein B, and rare diseases in infants

Research Abstract:

Neonatal respiratory distress syndrome due to pulmonary surfactant deficiency is the most frequent respiratory cause of morbidity and mortality among infants <1 year of age in the United States. Although disease pathogenesis has been attributed to developmental delay in pulmonary surfactant production, studies of gender, race, and twins demonstrate significant disease heritability (h2~0.2-0.8). Low frequencies of functional variants, allelic heterogeneity, low linkage disequilibrium in pulmonary surfactant metabolic network genes (SFTPB, SFTPC, and ABCA3), and natural selection against variants that disrupt neonatal lung function suggest that rare, high penetrance alleles of independent origin in multiple candidate genes and gene pathways account for disease heritability. Using race-specific, discovery and replication case-control cohorts, next generation sequencing platforms, and Combined Multivariate and Collapsing (CMC) statistical methods, we propose to test the hypothesis that excess, rare, functionally disruptive single nucleotide polymorphisms (SNPs) characterize genes and gene networks associated with increased risk of neonatal respiratory distress syndrome. First, to select a comprehensive, hierarchical list of candidate genes (~1,300) and their cognate gene networks expressed in human lung, we will use a candidate gene identification algorithm and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database. Secondly, to rank gene loci by race-specific disease risk, we will use exonic sequencing, in silico evaluation of exonic SNP function, CMC statistical methods, and separate European American and African American case-control cohorts sized to provide adequate statistical power (>0.8). Thirdly, to validate the ranking of gene loci by race-specific disease risk and to search for epistatic, network x network, and gene x environment interactions that confer disease risk, we will use exonic sequencing and CMC, Bayesian, and logic tree statistical methods in replication and merged case-control cohorts. The overall impact on child health of unraveling the genetic basis of neonatal respiratory distress syndrome includes reduction in neonatal morbidity and mortality through development of clinically useful diagnostic tools and identification of novel therapeutic targets to prevent genetic disruption of pulmonary surfactant metabolism.

Mentorship and Commitment to Diversity Statement:
Dr. Cole has mentored more than 100 trainees from high school students to post-doctoral scientists and junior faculty members. He is committed to mentoring through listening, problem solving, nurturing, and critical thinking and to an inclusive, supportive, and scientifically rigorous environment

Selected Publications:

Viehl L, Wegner DJ, Hmiel SP, White FV, Jain S, Cole FS, Wambach JA. Lethal neonatal respiratory failure due to biallelic variants in BBS1 and monoallelic variant in TTC21B. Pediatr Nephrol 2022; doi: 10.1007/s00467-022-05616-z. Online ahead of print. PMID: 35695966

Kingsmore SF, Cole FS. The role of genome sequencing in neonatal intensive care units. Annu Rev Genomics Hum Genet 2022; 23:427-448. PMID: 35676073

Wambach JA, Nogee LM, Cole FS. First steps toward personalized therapies for ABCA3 deficiency. Am J Respir Cell Mol Biol. 2022; 66:349-350. PMID: 35077664

NICUSeq Study Group, Krantz ID, Medne L, Weatherly JM, Wild KT, Biswas S, Devkota B, Hartman T, Brunelli L, Fishler KP, Abdul-Rahman O, Euteneuer JC, Hoover D, Dimmock D, Cleary J, Farnaes L, Knight J, Schwarz AJ, Vargas-Shiraishi OM, Wigby K, Zadeh N, Shinawi M, Wambach JA, Baldridge D, Cole FS, Wegner DJ, Urraca N, Holtrop S, Mostafavi R, Mroczkowski HJ, Pivnick EK, Ward JC, Talati A, Brown CW, Belmont JW, Ortega JL, Robinson KD, Brocklehurst WT, Perry DL, Ajay SS, Hagelstrom RT, Bennett M, Rajan V, Taft RJ. Effect of whole-genome sequencing on the clinical management of acutely ill infants with suspected genetic disease: a randomized clinical trial. JAMA Pediatr. 2021; 175:1218-1226. PMID: 34570182

Alysandratos KD, Russo SJ, Petcherski A, Taddeo EP, Acín-Pérez R, Villacorta-Martin C, Jean JC, Mulugeta S, Rodriguez LR, Blum BC, Hekman RM, Hix OT, Minakin K, Vedaie M, Kook S, Tilston-Lunel AM, Varelas X, Wambach JA, Cole FS, Hamvas A, Young LR, Liesa M, Emili A, Guttentag SH, Shirihai OS, Beers MF, Kotton DN. Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease. Cell Rep. 2021; 36:109636. PMID: 34469722

Reynolds M, Linneman LA, Luna S, Warner BB, Turmelle YP, Kulkarni SS, Jiang X, Khanna G, Shinawi M, Porter FD, Ory DS, Cole FS, Dickson PI. A phase 1/2 open label nonrandomized clinical trial of intravenous 2-hydroxypropyl-beta-cyclodextrin for acute liver disease in infants with Niemann-Pick C1. Mol Genet Metab Rep. 2021;28:100772. PMID: 34113546

Luna SE, Wegner DJ, Gale S, Yang P, Hollander A, St Dennis-Feezle L, Nabhan ZM, Ory DS, Cole FS, Wambach JA. Whole exome sequencing and functional characterization increase diagnostic yield in siblings with a 46, XY difference of sexual development (DSD). J Steroid Biochem Mol Biol. 2021;212:105908. PMID: 33984517

Rosano KK, Wegner DJ, Shinawi M, Baldridge D, Bucelli RC, Dahiya S, White FV, Willing MC, McAllister W, Taft RJ, Bluske K, Buchanan A, Cole FS, Wambach JA. Biallalic ASCC1 variants including a novel intronic variant result in expanded phenotypic spectrum of spinal muscular atrophy with congenital bone fractures 2 (SMABF2). Am J Med Genet A. 2021;185:2190-2197. PMID: 33931933

Last Updated: 11/7/2022 12:44:01 PM

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