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

  • 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
  • de la Chapelle AIntronic miR-3151 Within BAALC Drives Leukemogenesis by Deregulating the TP53 Pathway.Sci Signal 7(321) 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
  • de la Chapelle ANRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation.Proc Natl Acad Sci U S A 111 4179-84 3/18/2014
  • Holinski-Feder EBiallelic MUTYH mutations can mimic Lynch syndrome.Eur J Hum Genet 2/12/2014
  • Peeters RPIdentification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.PLoS Genet 10 e1004123 2/1/2014
  • Goldberg RMProstate cancer incidence in males with Lynch syndrome.Genet Med 1/16/2014
  • 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(10) e76607 10/9/2013
  • de la Chapelle AUnraveling the genetic predisposition to differentiated thyroid carcinoma.J Clin Endocrinol Metab 98(10) 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
  • 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 in press 8/29/2013
  • Swierniak M, Wojcicka A, Czetwertynska M, Stachlewska E, Maciag M, Wiechno W, Gornicka B, Bogdanska M, Koperski L, de la Chapelle A, Jazdzewski KIn-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma.J Clin Endocrinol Metab 98(8) E1401-9 8/1/2013
  • de la Chapelle AHow do we approach the goal of identifying everybody with Lynch syndrome?Fam Cancer 12(2) 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, Jarzab B, de la Chapelle ASRGAP1 is a candidate gene for papillary thyroid carcinoma susceptibility.J Clin Endocrinol Metab 98(5) E973-80 5/1/2013
  • Tomsic J, Senter L, Liyanarachchi S, Clendenning M, Vaughn CP, Jenkins MA, Hopper JL, Young J, Samowitz W, de la Chapelle ARecurrent and founder mutations in the PMS2 gene.Clin Genet 83(3) 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(1) e55261 1/1/2013
  • 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 AUltra-rare mutation in long-range enhancer predisposes to thyroid carcinoma with high penetrance.PLoS One 8(5) e61920 1/1/2013
  • Moreira L, Balaguer F, Lindor N, de la Chapelle A, 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, Castells AIdentification of Lynch syndrome among patients with colorectal cancer.JAMA 308(15) 1555-65 10/17/2012
  • Tanner SM, Sturm AC, Baack EC, Liyanarachchi S, de la Chapelle AInherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns.Orphanet J Rare Dis 7 56 8/28/2012
  • Nagy R, Wang H, Albrecht B, Wieczorek D, Gillessen-Kaesbach G, Haan E, Meinecke P, de la Chapelle A, Westman JAMicrocephalic osteodysplastic primordial dwarfism type I with biallelic mutations in the RNU4ATAC gene.Clin Genet 82(2) 140-6 8/1/2012
  • Eisfeld AK, Marcucci G, Maharry K, Schwind S, Radmacher MD, Nicolet D, Becker H, Mrózek K, Whitman SP, Metzeler KH, Mendler JH, Wu YZ, Liyanarachchi S, Patel R, Baer MR, Powell BL, Carter TH, Moore JO, Kolitz JE, Wetzler M, Caligiuri MA, Larson RA, Tanner SM, de la Chapelle A, Bloomfield CDmiR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia.Blood 120(2) 249-58 7/12/2012
  • Mercado RC, Hampel H, Kastrinos F, Steyerberg E, Balmana J, Stoffel E, Cohn DE, Backes FJ, Hopper JL, Jenkins MA, Lindor NM, Casey G, Haile R, Madhavan S, de la Chapelle A, Syngal SPerformance of PREMM(1,2,6), MMRpredict, and MMRpro in detecting Lynch syndrome among endometrial cancer cases.Genet Med 14(7) 670-80 7/1/2012
  • Jendrzejewski J, He H, Radomska HS, Li W, Tomsic J, Liyanarachchi S, Davuluri RV, Nagy R, de la Chapelle AThe polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type.Proc Natl Acad Sci U S A 109(22) 8646-51 5/29/2012
  • Tomsic J, Liyanarachchi S, Hampel H, Morak M, Thomas BC, Raymond VM, Chittenden A, Schackert HK, Gruber SB, Syngal S, Viel A, Holinski-Feder E, Thibodeau SN, de la Chapelle AAn American founder mutation in MLH1.Int J Cancer 130(9) 2088-95 5/1/2012
  • Win AK, Walters RJ, Buchanan DD, Jenkins MA, Sweet K, Frankel WL, de la Chapelle A, McKeone DM, Walsh MD, Clendenning M, Pearson SA, Pavluk E, Nagler B, Hopper JL, Gattas MR, Goldblatt J, George J, Suthers GK, Phillips KD, Woodall S, Arnold J, Tucker K, Field M, Greening S, Gallinger S, Aronson M, Perrier R, Woods MO, Green JS, Walker N, Rosty C, Parry S, Young JPCancer risks for relatives of patients with serrated polyposis.Am J Gastroenterol 107(5) 770-8 5/1/2012

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