Publications

2023

Inherited cancer predisposing mutations in patients with therapy-related myeloid neoplasms. Shih AJ, Jun T, Skol AD, Bao R, Huang L, Vora S, McNerney ME, Hungate EA, Le Beau MM, Larson RA, Elliott A, Lu HM, Huether R, Hernandez F, Stölzel F, Allan JM, Onel K. Br J Haematol. 2023 Feb;200(4):489-493. doi: 10.1111/bjh.18543. Epub 2022 Nov 9.

2021

Real-world Evidence of Diagnostic Testing and Treatment Patterns in US Patients With Breast Cancer With Implications for Treatment Biomarkers From RNA Sequencing Data. Fernandes LE, Epstein CG, Bobe AM, Bell JSK, Stumpe MC, Salazar ME, Salahudeen AA, Pe Benito RA, McCarter C, Leibowitz BD, Kase M, Igartua C, Huether R, Hafez A, Beaubier N, Axelson MD, Pegram MD, Sammons SL, O'Shaughnessy JA, Palmer GA. Clin Breast Cancer. 2021 Aug;21(4):e340-e361. doi: 10.1016/j.clbc.2020.11.012. Epub 2020 Dec 18.

Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants. Fortuno C, Lee K, Olivier M, Pesaran T, Mai PL, de Andrade KC, Attardi LD, Crowley S, Evans DG, Feng BJ, Foreman AKM, Frone MN, Huether R, James PA, McGoldrick K, Mester J, Seifert BA, Slavin TP, Witkowski L, Zhang L, Plon SE, Spurdle AB, Savage SA; ClinGen TP53 Variant Curation Expert Panel. Hum Mutat. 2021 Mar;42(3):223-236.

2020

Tumor Mutational Burden From Tumor-Only Sequencing Compared With Germline Subtraction From Paired Tumor and Normal Specimens. Parikh K, Huether R, White K, Hoskinson D, Beaubier N, Dong H, Adjei AA, Mansfield AS. JAMA Netw Open. 2020 Feb 5;3(2):e200202

Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy. Carvill GL, Helbig KL, Myers CT, Scala M, Huether R, Lewis S, Kruer TN, Guida BS, Bakhtiari S, Sebe J, Tang S, Stickney H, Oktay SU, Bhandiwad AA, Ramsey K, Narayanan V, Feyma T, Rohena LO, Accogli A, Severino M, Hollingsworth G, Gill D, Depienne C, Nava C, Sadleir LG, Caruso PA, Lin AE, Jansen FE, Koeleman B, Brilstra E, Willemsen MH, Kleefstra T, Sa J, Mathieu ML, Perrin L, Lesca G, Striano P, Casari G, Scheffer IE, Raible D, Sattlegger E, Capra V, Padilla-Lopez S, Mefford HC, Kruer MC Hum Mutat. 2020 Jul;41(7):1263-1279.

2019

Integrated genomic profiling expands clinical options for patients with cancer. Beaubier N, Bontrager M, Huether R, Igartua C, Lau D, Tell R, Bobe AM, Bush S, Chang AL, Hoskinson DC, Khan AA, Kudalkar E, Leibowitz BD, Lozachmeur A, Michuda J, Parsons J, Perera JF, Salahudeen A, Shah KP, Taxter T, Zhu W, White KP. Nat Biotechnol. 2019 Nov;37(11):1351-1360. doi: 10.1038/s41587-019-0259-z

Clinical validation of the tempus xT next-generation targeted oncology sequencing assay. Beaubier N, Tell R, Lau D, Parsons JR, Bush S, Perera J, Sorrells S, Baker T, Chang A, Michuda J, Iguartua C, MacNeil S, Shah K, Ellis P, Yeatts K, Mahon B, Taxter T, Bontrager M, Khan A, Huether R, Lefkofsky E, White KP. Oncotarget. 2019 Mar 22;10(24):2384-2396

Mutations in MAP3K1 that cause 46,XY disorders of sex development disrupt distinct structural domains in the protein. Chamberlin A, Huether R, Machado AZ, Groden M, Liu HM, Upadhyay K, O V, Gomes NL, Lerario AM, Nishi MY, Costa EMF, Mendonca B, Domenice S, Velasco J, Loke J, Ostrer H. Hum Mol Genet. 2019 May 15;28(10):1620-1628.

2018

Gene-specific criteria for PTEN variant curation: Recommendations from the ClinGen PTEN Expert Panel. Mester JL, Ghosh R, Pesaran T, Huether R, Karam R, Hruska KS, Costa HA, Lachlan K, Ngeow J, Barnholtz-Sloan J, Sesock K, Hernandez F, Zhang L, Milko L, Plon SE, Hegde M, Eng C. Hum Mutat. 2018 Nov;39(11):1581-1592.

Association of Breast and Ovarian Cancers With Predisposition Genes Identified by Large-Scale Sequencing. Lu HM, Li S, Black MH, Lee S, Hoiness R, Wu S, Mu W, Huether R, Chen J, Sridhar S, Tian Y, McFarland R, Dolinsky J, Tippin Davis B, Mexal S, Dunlop C, Elliott A. JAMA Oncol. 2018 Aug 16.

Clinical validation of the Tempus xO assay. Beaubier N, Tell R, Huether R, Bontrager M, Bush S, Parsons J, Shah K, Baker T, Selkov G, Taxter T, Thomas A, Bettis S, Khan A, Lau D, Lee C, Barber M, Cieslik M, Frankenberger C, Franzen A, Weiner A, Palmer G, Lonigro R, Robinson D, Wu YM, Cao X, Lefkofsky E, Chinnaiyan A, White KP. Oncotarget. 2018 May 25;9(40):25826-25832.

Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Ma X, Liu Y, Liu Y, Alexandrov LB, Edmonson MN, Gawad C, Zhou X, Li Y, Rusch MC, Easton J, Huether R, Gonzalez-Pena V, Wilkinson MR, Hermida LC, Davis S, Sioson E, Pounds S, Cao X, Ries RE, Wang Z, Chen X, Dong L, Diskin SJ, Smith MA, Guidry Auvil JM, Meltzer PS, Lau CC, Perlman EJ, Maris JM, Meshinchi S, Hunger SP, Gerhard DS, Zhang J. Nature. 2018 Feb 28.

2017

De Novo Variants in KLF7 are a Potential Novel Cause of Developmental Delay/Intellectual Disability, Neuromuscular and Psychiatric Symptoms. Powis Z, Petrik I, Cohen JS, Escolar D, Burton J, van Ravenswaaij-Arts CMA, Sival DA, Stegmann APA, Kleefstra T, Pfundt R, Chikarmane R, Begtrup A, Huether R, Tang S, Shinde DN. Clin Genet. 2017 Dec 18.

Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance. Powis Z, Farwell Hagman KD, Mroske C, McWalter K, Cohen JS, Colombo R, Serretti A, Fatemi A, David KL, Reynolds J, Immken LD, Nagakura H, Cunniff C, Payne K, Barbaro-Dieber T, Gripp KW, Baker L, Stamper T, Aleck KA, Jordan ES, Hersh J, Burton J, Wentzensen IM, Guillen Sacoto MJ, Willaert R, Cho MT, Petrik I, Huether R, Tang S. Clin Genet. 2017 Sep 7.

DNM1 encephalopathy: A new disease of vesicle fission. von Spiczak S, Helbig KL, Shinde DN, Huether R, Pendziwiat M, Lourenço C, Nunes ME, Sarco DP, Kaplan RA, Dlugos DJ, Kirsch H, Slavotinek A, Cilio MR, Cervenka MC, Cohen JS, McClellan R, Fatemi A, Yuen A, Sagawa Y, Littlejohn R, McLean SD, Hernandez-Hernandez L, Maher B, Møller RS, Palmer E, Lawson JA, Campbell CA, Joshi CN, Kolbe DL, Hollingsworth G, Neubauer BA, Muhle H, Stephani U, Scheffer IE, Pena SDJ, Sisodiya SM, Helbig I; Epi4K Consortium; EuroEPINOMICS-RES NLES Working Group. Neurology. 2017 Jul 25;89(4):385-394.

Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. Couch FJ, Shimelis H, Hu C, Hart SN, Polley EC, Na J, Hallberg E, Moore R, Thomas A, Lilyquist J, Feng B, McFarland R, Pesaran T, Huether R, LaDuca H, Chao EC, Goldgar DE, Dolinsky JS. JAMA Oncol. 2017

2016

Beyond DNA: An Integrated and Functional Approach for Classifying Germline Variants in Breast Cancer Genes T. Pesaran, R. Karam, R. Huether, S. Li, S. Farber-Katz, A. Chamberlin, H. Chong, H. LaDuca, and A. Elliott. International Journal of Breast Cancer. Int J Breast Cancer. 2016, 2469523

The genomic landscape of core-binding factor acute myeloid leukemias. Faber ZJ, Chen X, Gedman AL, Boggs K, Cheng J, Ma J, Radtke I, Chao JR, Walsh MP, Song G, Andersson AK, Dang J, Dong L, Liu Y, Huether R, Cai Z, Mulder H, Wu G, Edmonson M, Rusch M, Qu C, Li Y, Vadodaria B, Wang J, Hedlund E, Cao X, Yergeau D, Nakitandwe J, Pounds SB, Shurtleff S, Fulton RS, Fulton LL, Easton J, Parganas E, Pui CH, Rubnitz JE, Ding L, Mardis ER, Wilson RK, Gruber TA, Mullighan CG, Schlenk RF, Paschka P, Döhner K, Döhner H, Bullinger L, Zhang J, Klco JM, Downing JR. Nat Genet. 2016 Oct 31.

Further evidence that de novo missense and truncating variants in ZBTB18 cause intellectual disability with variable features. Cohen JS, Srivastava S, Farwell Hagman KD, Shinde DN, Huether R, Darcy D, Wallerstein R, Houge G, Berland S, Monaghan KG, Poretti A, Wilson AL, Chung WK, Fatemi A. Clin Genet. 2016 Sep 6. doi: 10.1111/cge.12861.

Several rare genetic variants were identified in patients with intellectual disability, corpus callosum abnormalities, and microcephaly.
Missense variants were localized to the DNA binding Zinc finger domains and further sequence and structural investigation showed two alterations, identified in the most phenotypically severe patients with missense alterations, occurred in the +3 and +6 positions required for DNA specificity in Zinc finger proteins. Another missense alteration was identified and was observed between the di-histidine motif which structurally was anticipated to modulate the DNA binding action of an adjacent Zinc finger.
The observed phenotypic severity can be explained by the importance of the position within the Zinc finger domain.

A Recurrent Mutation in KCNA2 as a Novel Cause of Hereditary Spastic Paraplegia and Ataxia. Helbig KL, Hedrich UB, Shinde DN, Krey I, Teichmann AC, Hentschel J, Schubert J, Chamberlin AC, Huether R, Lu HM, Alcaraz WA, Tang S, Jungbluth C, Dugan SL, Vainionpää L, Karle KN, Synofzik M, Schöls L, Schüle R, Lehesjoki AE, Helbig I, Lerche H, Lemke JR. Ann Neurol. 2016 Aug 20. doi: 10.1002/ana.24762.

Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnosed diseases. Farwell Hagman KD, Shinde DN, Mroske C, Smith E, Radtke K, Shahmirzadi L, El-Khechen D, Powis Z, Chao EC, Alcaraz WA, Helbig KL, Sajan SA, Rossi M, Lu HM, Huether R, Li S, Wu S, Nuñes ME, Tang S. Genet Med. 2016 Aug 11. doi: 10.1038/gim.2016.95.

Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy. Rudolf G, Lesca G, Mehrjouy MM, Labalme A, Salmi M, Bache I, Bruneau N, Pendziwiat M, Fluss J, de Bellescize J, Scholly J, Møller RS, Craiu D, Tommerup N, Valenti-Hirsch MP, Schluth-Bolard C, Sloan-Béna F, Helbig KL, Weckhuysen S, Edery P, Coulbaut S, Abbas M, Scheffer IE, Tang S, Myers CT, Stamberger H, Carvill GL, Shinde DN, Mefford HC, Neagu E, Huether R, Lu HM, Dica A, Cohen JS, Iliescu C, Pomeran C, Rubenstein J, Helbig I, Sanlaville D, Hirsch E, Szepetowski P. Eur J Hum Genet. 2016 Jun 29. doi: 10.1038/ejhg.2016.80

2015

Mutations in RASA1 and GDF2 identified in patients with clinical features of hereditary hemorrhagic telangiectasia Hernandez F., Huether R., Carter L., Johnston T., Thompson J., Gossage JR., Chao E., Elliott EM. Human Genome Variation 2015, 2:15040

Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities Mroske C., Rasmussen K., Shinde DN., Huether R., Powis Z., Lu H., Baxter RM., McPherson E., Tang S. BMC Medical Genetics 2015, 16:102

Pax5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic leukemia. Dang J, Wei L, de Ridder J, Su X, Rust AG, Roberts KG, Payne-Turner D, Cheng J, Ma J, Qu C, Wu G, Song G, Huether R, Schulman B, Janke L, Zhang J, Downing JR, van der Weyden L, Adams DJ, Mullighan CG. Blood. 2015 Apr 8.

The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Andersson AK, Ma J, Wang J, Chen X, Gedman AL, Dang J, Nakitandwe J, Holmfeldt L, Parker M, Easton J, Huether R, Kriwacki R, Rusch M, Wu G, Li Y, Mulder H, Raimondi S, Pounds S, Kang G, Shi L, Becksfort J, Gupta P, Payne-Turner D, Vadodaria B, Boggs K, Yergeau D, Manne J, Song G, Edmonson M, Nagahawatte P, Wei L, Cheng C, Pei D, Sutton R, Venn NC, Chetcuti A, Rush A, Catchpoole D, Heldrup J, Fioretos T, Lu C, Ding L, Pui CH, Shurtleff S, Mullighan CG, Mardis ER, Wilson RK, Gruber TA, Zhang J, Downing JR; St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. Nature Genetics 2015 Apr;47(4):330-7.

2014

The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Huether R, Dong L, Chen X, Wu G, Parker M, Wei L, Ma J, Edmonson MN, Hedlund EK, Rusch MC, Shurtleff SA, Mulder HL, Boggs K, Vadordaria B, Cheng J, Yergeau D, Song G, Becksfort J, Lemmon G, Weber C, Cai Z, Dang J, Walsh M, Gedman AL, Faber Z, Easton J, Gruber T, Kriwacki RW, Partridge JF, Ding L, Wilson RK, Mardis ER, Mullighan CG, Gilbertson RJ, Baker SJ, Zambetti G, Ellison DW, Zhang J, Downing JR. Nature Communication. 2014 Apr 8;5:3630.

Survival analysis of infected mice reveals pathogenic variations in the genome of avian H1N1 viruses. Koçer ZA, Fan Y, Huether R, Obenauer J, Webby RJ, Zhang J, Webster RG, Wu G. Scientific Reports. 2014 Dec 12;4:7455.

The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ; St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. Nature Genetics 2014 May;46(5):444-50.

C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs K, Yergeau D, Vadodaria B, Mulder HL, Becksfort J, Gupta P, Huether R, Ma J, Song G, Gajjar A, Merchant T, Boop F, Smith AA, Ding L, Lu C, Ochoa K, Zhao D, Fulton RS, Fulton LL, Mardis ER, Wilson RK, Downing JR, Green DR, Zhang J, Ellison DW, Gilbertson RJ. Nature. 2014 Feb 27;506(7489):451-5.

RB1 gene inactivation by chromothripsis in human retinoblastoma. McEvoy J, Nagahawatte P, Finkelstein D, Richards-Yutz J, Valentine M, Ma J, Mullighan C, Song G, Chen X, Wilson M, Brennan R, Pounds S, Becksfort J, Huether R, Lu C, Fulton RS, Fulton LL, Hong X, Dooling DJ, Ochoa K, Mardis ER, Wilson RK, Easton J, Zhang J, Downing JR, Ganguly A, Dyer MA. Oncotarget. 2014 Jan 30;5(2):438-50.

2013

Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Jaffe JD, Wang Y, Chan HM, Zhang J, Huether R, Kryukov GV, Bhang HE, Taylor JE, Hu M, Englund NP, Yan F, Wang Z, Robert McDonald E 3rd, Wei L, Ma J, Easton J, Yu Z, deBeaumount R, Gibaja V, Venkatesan K, Schlegel R, Sellers WR, Keen N, Liu J, Caponigro G, Barretina J, Cooke VG, Mullighan C, Carr SA, Downing JR, Garraway LA, Stegmeier F. Nature Genetics 2013 Nov;45(11):1386-91.

Several recurrent mutations were concurrently discovered in the SET domain of NSD2. through Mass Spec studies and NGS capture study of pediatric leukemia cells.
A multi-structure homology model was generated to interpret the NSD2 mutations.
The variants are located in the SET domain at the SET- Histone 3 binding interface and a change in charge results in a enhanced binding, confirmed through experimental studies showing the mutations result in an increase in H3K36 methylation and enhanced cell growth.

Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW; St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project. Nature Genetics 2013 Jun;45(6):602-12.

A recurrent duplication of FGFR1 kinase domain was uncovered by WGS in a subtype of low-grade gliomas.
Based on linker lengths obtained from the WGS FGFR1 data, a dual-kinase structural model was generated. The model I generated indicated that the linker is of sufficient size and flexibility to auto-phosphorylate the kinase in both cis and trans.
Different linker lengths were experimentally tested for auto-phosphorylation and downstream activation. We observed that a di-kinase without linker could still auto-phosphorylate but not activate the MAPK pathway, and ligand independent auto-phosporylation was observed with most partially kinase dead mutants but could not activate MAPK pathway. Together these point to an initial activation in cis. However, further activation by trans could not be ruled out.

The genomic landscape of hypodiploid acute lymphoblastic leukemia. Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen SC, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Phillips LA, Song G, Easton J, Parker M, Chen X, Rusch M, Boggs K, Vadodaria B, Hedlund E, Drenberg C, Baker S, Pei D, Cheng C, Huether R, Lu C, Fulton RS, Fulton LL, Tabib Y, Dooling DJ, Ochoa K, Minden M, Lewis ID, To LB, Marlton P, Roberts AW, Raca G, Stock W, Neale G, Drexler HG, Dickins RA, Ellison DW, Shurtleff SA, Pui CH, Ribeiro RC, Devidas M, Carroll AJ, Heerema NA, Wood B, Borowitz MJ, Gastier-Foster JM, Raimondi SC, Mardis ER, Wilson RK, Downing JR, Hunger SP, Loh ML, Mullighan CG. Nature Genetics 2013 Mar;45(3):242-52.

2012

Novel mutations target distinct subgroups of medulloblastoma. Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, Phoenix TN, Hedlund E, Wei L, Zhu X, Chalhoub N, Baker SJ, Huether R, Kriwacki R, Curley N, Thiruvenkatam R, Wang J, Wu G, Rusch M, Hong X, Becksfort J, Gupta P, Ma J, Easton J, Vadodaria B, Onar-Thomas A, Lin T, Li S, Pounds S, Paugh S, Zhao D, Kawauchi D, Roussel MF, Finkelstein D, Ellison DW, Lau CC, Bouffet E, Hassall T, Gururangan S, Cohn R, Fulton RS, Fulton LL, Dooling DJ, Ochoa K, Gajjar A, Mardis ER, Wilson RK, Downing JR, Zhang J, Gilbertson RJ. Nature. 2012 Aug 2;488(7409):43-8.

Whole genome sequencing of Medulloblastomas tumors revealed several recurrent mutations in the gene DDX3X.
DDX3X is a essential multifunctional RNA binding protein. Interestingly, siRNA knockdown of DDX3X leads to cell death but the observed point mutations resulted in cell survival.
The structural model I generated revealed the mutations localized to the RNA binding surface and not the ATP binding pocket, which indicate a disruption of protein-RNA interactions leaving other DDX3X functions, such protein/protein binding and ATP hydrolysis function intact.

The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG. Nature. 2012 Jan 11;481(7380):157-63.

A minimized homology model of the SET domain in the histone methyltransferase EZH2 revealed mutations observed in T-cell precursor acute lymphoblastic leukaemia would have deleterious effects on enzyme activity.
The mutations drastically alter the SET domain fold and the binding of the cofactor (SAM), resulting in a loss of enzyme function.

Evolution of bacterial ribosomal protein L1. Duax WL, Huether R, Dziak D. Int J Bioinform Res Appl. 2012;8(1-2):99-111.

Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Zhang J, Baker SJ; St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. Nat Genet. 2012 Jan 29;44(3):251-3.

2011

Structural and Bioinformatic studies of the short chain oxidoreductase enzymes. Huether, R. Doctoral dissertation, University of Buffalo, Buffalo New York, USA.

2010

The short-chain oxidoreductase Q9HYA2 from Pseudomonas aeruginosa PAO1 contains an atypical catalytic center. Huether R, Mao Q, Duax WL, Umland TC. Protein Sci. 2010 May;19(5):1097-103.

Sequence fingerprint and structural analysis of the SCOR enzyme A3DFK9 from Clostridium thermocellum. Huether R, Liu ZJ, Xu H, Wang BC, Pletnev VZ, Mao Q, Duax WL, Umland TC. Proteins. 2010 Feb 15;78(3):603-13.

2009

Divergent evolution of a Rossmann fold and identification of its oldest surviving ancestor. Duax WL, Huether R, Pletnev V, Umland TC; Charles M. Weeks. Int J Bioinform Res Appl. 2009;5(3):280-94.

2007

Structure/function of human type 1 3beta-hydroxysteroid dehydrogenase: An intrasubunit disulfide bond in the Rossmann-fold domain and a Cys residue in the active site are critical for substrate and coenzyme utilization. Thomas JL, Huether R, Mack VL, Scaccia LA, Stoner RC, Duax WL. J Steroid Biochem Mol Biol. 2007 Oct;107(1-2):80-7.

Rational proteomics of PKD1. I. Modeling the three dimensional structure and ligand specificity of the C_lectin binding domain of Polycystin-1. Pletnev V, Huether R, Habegger L, Schultz W, Duax W. J Mol Model. 2007 Aug;13(8):891-6.

2005

Determining structure and function of steroid dehydrogenase enzymes by sequence analysis, homology modeling, and rational mutational analysis. Duax WL, Thomas J, Pletnev V, Addlagatta A, Huether R, Habegger L, Weeks CM. Ann N Y Acad Sci. 2005 Dec;1061:135-48.

Rational genomics I: antisense open reading frames and codon bias in short-chain oxido reductase enzymes and the evolution of the genetic code. Duax WL, Huether R, Pletnev VZ, Langs D, Addlagatta A, Connare S, Habegger L, Gill J. Proteins. 2005 Dec 1;61(4):900-6.

Robert Huether

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