Albert de la Chapelle, MD, PhD
Professor, Department of Molecular Virology, Immunology and Medical Genetics

 

804 Biomedical Research Tower

460 W 12th Ave

Columbus, OH 43210

Phone: (614) 688-4781
Fax: (614) 688-4772
albert.delachapelle@osumc.edu

Special Interests

Research in Dr. de la Chapelle’s laboratory focuses on the mapping, cloning, and characterization of high- and low-penetrance genes for cancer predisposition.  When new genes are identified, studies are directed to determine the pathophysiological role of the proteins or RNA molecules 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 include colorectal cancer, papillary thyroid cancer, acute myeloid leukemia and chronic lymphocytic leukemia.   Colorectal cancer is highly heritable; but only a fraction of all predisposing genes have been detected so far.  Even so, screening all colorectal and endometrial cancer patients for mutations in the mismatch repair genes (Lynch syndrome) is practically feasible and desirable, because it can save lives through clinical surveillance of targeted high-risk family members.  A method of population-wide screening for Lynch syndrome has been developed and its nationwide use is being encouraged.  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.  The underlying mechanism is being investigated. Moreover, several novel candidate genes are investigated that predispose to thyroid cancer.  Second-generation deep sequencing is replacing previously used methods in the search for deleterious mutations.  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 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. In chronic lymphocytic leukemia the role of the proapoptotic gene DAPK1 is investigated, and in families with several affected individuals novel predisposing genes are sought by second-generation deep sequencing.

Education

MD, University of Helsinki, FI, 1957
PhD, Human Genetics, Univ. of Helsinki, FI, 1962
Internship/Residency: University of Helsinki, FI, 1965
Subspecialty Training: University of Helsinki, FI, 1986
Postdoctoral Training: Biochemistry, Columbia University, 1968
 

Select Publications

Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomäki P, Chadwick RB, Kääriänen H, Percesepe A, Ahtola H, Härkönen N, Julkunen R, Kangas E, Ojala S, Tulikoura J, Valkamo E, Eskelinen M, Järvinen H, Mecklin JP, de la Chapelle A: Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. New Engl J Med 338:1481-1487, 1998

Tanner SM, Austin JL, Leone G, Rush LJ, Plass C, Heinonen K, Mrozek K, Sill H, Knuutila S, Kolitz JE, Archer KJ, Caligiuri MA, Bloomfield CD, de la Chapelle A: BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia. Proc Natl Acad Sci USA 98:13901-13096, 2001

Huang Y, Prasad M, Lemon WJ, Hampel H, Wright FA, Kornacker K, LiVolsi V, Frankel W, Kloos RT, Eng C, Pellegata NS, de la Chapelle A: Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci USA 98:15044-15049, 2001

Tanner SM, Aminoff M, Wright FA, Liyanarachchi S, Kuronen M, Saarinen A, Massika O, Mandel H, Broch H, de la Chapelle A: Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia. Nature Genet 33:426-429, 2003

Lynch HT, Coronel SM, Okimoto R, Hampel H, Sweet K, Lynch JF, Barrows A, Wijnen J, van der Klift H, Franken P, Wagner A, Fodde R, de la Chapelle A: A founder mutation of the MSH2 gene and hereditary nonpolyposis colorectal cancer in the United States. JAMA 291:718-724, 2004

Baldus CD, Liyanarachchi S, Mrozek K, Auer H, Tanner SM, Guimond M, Ruppert AS, Mohamed N, Davuluri RV, Caligiuri MA, Bloomfield CD, de la Chapelle A: Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21:amplification discloses overexpression of APP, ETS2 and ERG genes, PNAS 101:3915-3920, 2004

Tanner SM, Li Z, Perko JD, Oner C, Cetin M, Altay C, Yurtsever Z, David KL, Faivre L, Ismail EA, Grasbeck R, de la Chapelle A: Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene. Proc Natl Acad Sci U S A. 102:4130-4133, 2005

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A: Screening for the Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) New Engl J Med 352:1851-1860, 2005

He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu C-G, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A: The role of micro-RNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 102:19075-19080, 2005

Hampel H, Frankel W, Panescu J, Lockman J, Sotamaa K, Fix D, Comeras I, LaJeunesse J, Nakagawa H, Westman JA, Prior TW, Clendenning M, Penzone P, Lombardi J, Dunn P, Cohn D, Copeland L, Eaton L, Fowler J, Lewandowski G, Vaccarello L, Bell J, Reid G, de la Chapelle A: Screening for Lynch Syndrome (HNPCC) among endometrial cancer patients. Cancer Res 66:7810-7817, 2006 

Raval A, Tanner S, Byrd J, Angerman E, Perko J, Chen S-S, Grever M, Lucas D, Matkovic J, Lin T, Kipps T, Murry F, Weisenburger D, Sanger W, Lynch J, Watson P, Jansen M, Yoshinaga Y, Rosenquist R, de Jong P, Coggill P, Beck S, Lynch H, de la Chapelle A, Plass C: Down-regulation of death associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell 129:879-890, 2007
 
Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Clendenning M, Sotamaa K, Prior T, Westman JA, Panescu J, Fix D, Lockman J, Lajeunesse J, Comeras I, de la Chapelle A.  Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal Cancer.  J Clin Oncol. 26:5783-5788, 2008

Bonafé L, Hastbacka J, de la Chapelle A, Campos-Xavier AB, Chiesa C, Forlino A, Superti-Furga A, Rossi A.  A novel mutation in the sulphate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia.  J Med Genet. 45:827-831, 2008

Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, Zeng Q, Zhang HT, Pennison MJ, Sadim M, Pasche B, Tanner SM, de la Chapelle A. Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science  321(5894):1361-1365, 2008

Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B, de la Chapelle A: Polymorphic mature micro RNAs from passenge rstrand of pre-miR-146a contribute to thyroid cancer.  PNAS 106:1502-1505, 2009

Gudmundsson J, Sulem P, Gudbjartsswon DF, Jonasson JG, Sigurdsson A, Bergthorsson JT, He H, Blondal T, Geller F, Jakobsdottir M, Magnusdottir DN, Matthiasdottir S, Stacey SN, Skarphedinsson OB, Helgadottir H, Li W, Nagy R, Aguillo E, Faure E, Prats E, Saez B, Martinez M, Eyjolfsson GI, Bjornsdottir US, Holm H,Kristjansson K, Frigge ML, Kristvinsson H, Gulcher JR, Jonsson T, Rafnar T, Hjartarson H, Mayordomo JI, de la Chpaelle A, Hrafnkelsson J, Thorsteinsdottir U, Kong A, Stefansson K: Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.  Nature Genet 41:460-464, 2009

de la chapelle A, Hampel H: Clinical relevance of Microsatellite instabiity in colorectal cancer.  J Clin Oncol 28:3380-3387, 2010

He H, Liyanarachchi S, Akagi K, Nagy R, Li J, Dietrich RC, Li W, Sebastian N, Wen B, Xin B, Singh J, Yan P, Alder H, Haan E, Wieczorek D, Albrecht B, Puffenberger E, Wang H, Westman JA, Padgett RA, Symer DE, de la Chapelle A: Mutations in U4atac snRNA, a component of the minor Spliceosome, in the developmental disorder MOPD1. Science 332:238-240, 2011www.sciencemag.org/cgi/rapidpdf/332/6026/238