Albert de la Chapelle MD, PhD


Albert de la Chapelle MD, PhD
ProfessorCollege of Medicinede-la-chapelle.1@osu.edu
804 Biomedical Research Tower 460 W 12th Avenue Columbus Ohio 43210
Phone:614-688-4781Fax: (614) 688-4763
  • Molecular Biology and Cancer Genetics

General Research Interest

Cancer Genetics and Genomics

Research Description

Research in Dr. de la Chapelle’s laboratory focuses on the mapping, cloning, and characterization of high-penetrance genes for cancer predisposition.  Similar studies into low-penetrance genes, a relatively new concept, are also done.  When new genes are identified, studies are directed to determine the pathophysiological role of the proteins they encode, and the mechanisms by which mutations in the genes contribute to the cancer phenotype. Finally, there is an emphasis on translational aspects of the research, viz. the exploitation of laboratory discoveries towards new diagnostic and therapeutic procedures.  Diseases under study in the de la Chapelle laboratory include colorectal cancer, papillary thyroid cancer, and acute myeloid leukemia.   Colorectal cancer is highly heritable; nevertheless only a small fraction of all predisposing genes have been detected so far.  Two novel mechanisms of predisposition to colorectal cancer are presently being explored. In papillary thyroid cancer predisposing germline mutations are sought by a variety of methods, including linkage, allelic association, and the determination of allelic differences in gene expression.  The role of non-coding RNA genes is emerging as a major cause of predisposition to papillary thyroid cancer.  One microRNA, 146a, has been implicated.  Carriers of a single nucleotide polymorphism in the pre-miR146a sequence have an elevated risk of thyroid cancer. It appears that heterozygotes for the polymorphism produce two abnormal mature miRs, whose target genes suggest the involvement of numerous downstream genes contributing to cancer development. In acute myeloid leukemia the group cloned a novel gene, BAALC for Brain and Acute Leukemia, Cytoplasmic that is expressed in early hematopoietic progenitor cells, and in a subset of the acute myeloid and lymphoid leukemias. Ongoing studies, including mouse modeling, aim at understanding the precise role of BAALC in leukemogenesis.  The working hypothesis is that BAALC is a marker of, or even a contributor to, blocked differentiation of these cells. 

Transinstitutional Work

The key to success in translational research is collaboration. OSU provides ample opportunities to collaborate, and  collaborations by the de la Chapelle lab extend within and beyond the Medical Center.  Almost all research projects are trans-institutional in some respect

Current Publications

  • Haraldsdottir S, Hampel H, Tomsic J, Frankel WL, Pearlman R, de la Chapelle A, Pritchard CCColon and Endometrial Cancers with Mismatch Repair Deficiency can Arise from Somatic, Rather Than Germline, Mutations.Gastroenterology in press 9/3/2014
  • Haraldsdottir S, Hampel H, Wei L, Wu C, Frankel W, Bekaii-Saab T, de la Chapelle A, Goldberg RMProstate cancer incidence in males with Lynch syndrome.Genet Med 16 553-7 7/1/2014
  • Wójcicka A, Czetwertyńska M, Świerniak M, Długosińska J, Maciąg M, Czajka A, Dymecka K, Kubiak A, Kot A, Płoski R, de la Chapelle A, Jażdżewski KVariants in the ATM-CHEK2-BRCA1 axis determine genetic predisposition and clinical presentation of papillary thyroid carcinoma.Genes Chromosomes Cancer 53 516-23 6/1/2014
  • Bloomfield CD, de la Chapelle A, Eisfeld AK, Schwind S, Patel R, Huang X, Santhanam R, Walker CJ, Markowitz J, Hoag KW, Jarvinen TM, Leffel B, Perrotti D, Carson WE 3rd, Marcucci GIntronic miR-3151 within BAALC drives leukemogenesis by deregulating the TP53 pathway.Sci Signal 7 ra36 4/15/2014
  • Wojcicka A, de la Chapelle A, Jazdzewski KMicroRNA-related sequence variations in human cancers.Hum Genet 133 463-9 4/1/2014
  • Markowitz J, Duan W, Otterson GA, Carson WE 3rd, Marcucci G, Bloomfield CD, de la Chapelle A, Eisfeld AK, Schwind S, Hoag KW, Walker CJ, Liyanarachchi S, Patel R, Huang XNRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation.Proc Natl Acad Sci U S A 111 4179-84 3/18/2014
  • Morak M, Heidenreich B, Keller G, Hampel H, Laner A, de la Chapelle A, Holinski-Feder EBiallelic MUTYH mutations can mimic Lynch syndrome.Eur J Hum Genet in press 2/12/2014
  • Korevaar TI, Plia MG, Sala C, Völker U, Richards JB, Sweep FC, Gieger C, Corre T, Kajantie E, Thuesen B, Taes YE, Visser WE, Hattersley AT, Kratzsch J, Hamilton A, Li W, Homuth G, Lobina M, Mariotti S, Soranzo N, Cocca M, Nauck M, Spielhagen C, Ross A, Arnold A, van de Bunt M, Liyanarachchi S, Heier M, Medici M, Porcu E, Pistis G, Teumer A, Brown SJ, Jensen RA, Rawal R, Roef GL, Plantinga TS, Vermeulen SH, Lahti J, Simmonds MJ, Husemoen LL, Freathy RM, Shields BM, Pietzner D, Nagy R, Broer L, Chaker L, Grabe HJ, Masciullo C, Galesloot TE, Lim EM, Reischl E, Leedman PJ, Lai S, Delitala A, Bremner AP, Philips DI, Beilby JP, Mulas A, Vocale M, Abecasis G, Forsen T, James A, Widen E, Hui J, Prokisch H, Rietzschel EE, Palotie A, Feddema P, Fletcher SJ, Schramm K, Rotter JI, Kluttig A, Radke D, Traglia M, Surdulescu GL, He H, Franklyn JA, Tiller D, Vaidya B, de Meyer T, Jørgensen T, Eriksson JG, O'Leary PC, Wichmann E, Hermus AR, Psaty BM, Ittermann T, Hofman A, Bosi E, Schlessinger D, Wallaschofski H, Pirastu N, Aulchenko YS, de la Chapelle A, Netea-Maier RT, Gough SC, Meyer Zu Schwabedissen H, Frayling TM, Kaufman JM, Linneberg A, Räikkönen K, Smit JW, Kiemeney LA, Rivadeneira F, Uitterlinden AG, Walsh JP, Meisinger C, den Heijer M, Visser TJ, Spector TD, Wilson SG, Völzke H, Cappola A, Toniolo D, Sanna S, Naitza S, Peeters RPIdentification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.PLoS Genet 10 e1004123 2/1/2014
  • Liyanarachchi S, Wojcicka A, Li W, Czetwertynska M, Stachlewska E, Nagy R, Hoag K, Wen B, Ploski R, Ringel MD, Kozłowicz-Gudzinska I, Gierlikowski W, Jazdzewski K, He H, de la Chapelle ACumulative risk impact of five genetic variants associated with papillary thyroid carcinoma.Thyroid 23 1532-40 12/1/2013
  • Jones KA, Kim PD, Patel BB, Kelsen SG, Braverman A, Swinton DJ, Gafken PR, Jones LA, Lane WS, Neveu JM, Leung HC, Shaffer SA, Leszyk JD, Stanley BA, Fox TE, Stanley A, Hall MJ, Hampel H, South CD, de la Chapelle A, Burt RW, Jones DA, Kopelovich L, Yeung ATImmunodepletion plasma proteomics by tripleTOF 5600 and Orbitrap elite/LTQ-Orbitrap Velos/Q exactive mass spectrometers.J Proteome Res 12 4351-65 10/4/2013
  • de la Chapelle AUnraveling the genetic predisposition to differentiated thyroid carcinoma.J Clin Endocrinol Metab 98 3974-6 10/1/2013
  • He H, Li W, Wu D, Nagy R, Liyanarachchi S, Akagi K, Jendrzejewski J, Jiao H, Hoag K, Wen B, Srinivas M, Waidyaratne G, Wang R, Wojcicka A, Lattimer IR, Stachlewska E, Czetwertynska M, Dlugosinska J, Gierlikowski W, Ploski R, Krawczyk M, Jazdzewski K, Kere J, Symer DE, Jin V, Wang Q, de la Chapelle ACorrection: Ultra-Rare Mutation in Long-Range Enhancer Predisposes to Thyroid Carcinoma with High Penetrance.PLoS One 8(9) 9/10/2013
  • Maciag M, Wiechno W, Gornicka B, Bogdanska M, Koperski L, de la Chapelle A, Jazdzewski K, Swierniak M, Wojcicka A, Czetwertynska M, Stachlewska EIn-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma.J Clin Endocrinol Metab 98 E1401-9 8/1/2013
  • Hampel H, de la Chapelle AHow do we approach the goal of identifying everybody with Lynch syndrome?Fam Cancer 12 313-7 6/1/2013
  • He H, Bronisz A, Liyanarachchi S, Nagy R, Li W, Huang Y, Akagi K, Saji M, Kula D, Wojcicka A, Sebastian N, Wen B, Puch Z, Kalemba M, Stachlewska E, Czetwertynska M, Dlugosinska J, Dymecka K, Ploski R, Krawczyk M, Morrison PJ, Ringel MD, Kloos RT, Jazdzewski K, Symer DE, Vieland VJ, Ostrowski M, Jarząb B, de la Chapelle ASRGAP1 is a candidate gene for papillary thyroid carcinoma susceptibility.J Clin Endocrinol Metab 98 E973-80 5/1/2013
  • Tomsic J, Senter L, Clendenning M, Vaughn CP, Jenkins MA, Hopper JL, Young J, Samowitz W, Liyanarachchi S, de la Chapelle ARecurrent and founder mutations in the PMS2 gene.Clin Genet 83 238-43 3/1/2013
  • Wei QX, Claus R, Hielscher T, Mertens D, Raval A, Oakes CC, Tanner SM, de la Chapelle A, Byrd JC, Stilgenbauer S, Plass CGermline allele-specific expression of DAPK1 in chronic lymphocytic leukemia.PLoS One 8 e55261 1/1/2013
  • Hertlein E, Beckwith KA, Lozanski G, Chen TL, Towns WH, Johnson AJ, Lehman A, Ruppert AS, Bolon B, Andritsos L, Lozanski A, Rassenti L, Zhao W, Jarvinen TM, Senter L, Croce CM, Symer DE, de la Chapelle A, Heerema NA, Byrd JCCharacterization of a new chronic lymphocytic leukemia cell line for mechanistic in vitro and in vivo studies relevant to disease.PLoS One 8 e76607 1/1/2013
  • Wojcicka A, Lattimer IR, Stachlewska E, Czetwertynska M, Dlugosinska J, Gierlikowski W, Ploski R, Krawczyk M, Jazdzewski K, Kere J, Symer DE, Jin V, Wang Q, de la Chapelle A, He H, Li W, Wu D, Nagy R, Liyanarachchi S, Akagi K, Jendrzejewski J, Jiao H, Hoag K, Wen B, Srinivas M, Waidyaratne G, Wang RUltra-rare mutation in long-range enhancer predisposes to thyroid carcinoma with high penetrance.PLoS One 8 e61920 1/1/2013
  • Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, Haile R, Thibodeau SN, Gunawardena S, Jenkins MA, Buchanan DD, Potter JD, Baron JA, Ahnen DJ, Moreno V, Andreu M, Ponz de Leon M, Rustgi AK, Moreira L, Balaguer F, Lindor N, de la Chapelle A, Castells A, EPICOLON ConsortiumIdentification of Lynch syndrome among patients with colorectal cancer.JAMA 308 1555-65 10/17/2012

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) 300 W. 10th Ave. Columbus, OH 43210 Phone: 1-800-293-5066 | Email: jamesline@osumc.edu