Mitchell Machiela, Sc.D., M.P.H.

Stadtman Investigator

Integrative Tumor Epidemiology Branch


9609 Medical Center Drive
Room SG/7E108
Rockville, MD 20850


Research Topics

Dr. Mitchell Machiela’s research is focused on understanding the role of inherited variation and acquired mutations in cancer risk. He is leading studies of large-scale genetic mosaicism to investigate the causes of acquired mosaic chromosomal alterations and their impact on cancer risk. He also conducts and analyzes genetic association studies to investigate the underlying genetic architecture of different cancers (e.g., pediatric and adult cancers).

Genetic Mosaicism

Genetic mosaicism results from an acquired DNA mutation that is present in some of the body's cells but not in others. A person with mosaicism has a mixture of normal and mutated cells. Dr. Machiela has published findings that estimate the frequency and distribution of mosaicism in existing genotyped populations of blood and buccal DNA. His research utilizes existing genotype data from DCEG studies and merged international consortia to enable well-powered investigations of mosaicism and cancer risk.

Relatively little is known of the mechanisms that initiate and select for mosaic alterations. Results from his previous work suggests inherited germline variation (e.g., at TCL1A) or environmental exposures (e.g., smoking) may predispose to mosaicism. Dr. Machiela is utilizing genotyped samples from DCEG special exposure and disease populations to examine endogenous and exogenous factors influencing acquisition of detectible mosaicism.

Acquired mosaic alterations have abundant potential to inform cancer etiology and drive oncogenic change. Dr. Machiela has found evidence suggesting mosaicism increases cancer risk for hematologic malignancies and select solid tumor subtypes. His research program continues to examine the influence of mosaicism on cancer risk in special exposure populations and various tissue types.

Genetic Architecture of Cancer

Dr. Machiela and colleagues have published several genome-wide association studies (GWAS) of common adult cancers. He is working to better understand the genomic architecture of cancer by performing genetic association studies in pediatric cancers and combining data on germline and somatic variation to better understand cancer genetic etiology and improve risk prediction.

Pediatric cancers like Ewing sarcoma (ES) provide a unique opportunity to study a homogenous tumor with potentially larger genetic contribution to risk. Dr. Machiela is leading a GWAS on ES to identify susceptibility regions and elucidate the underlying genetic architecture of ES. Findings from this ES GWAS have led to further regional sequencing to investigate germline-somatic interactions with ES fusion oncoproteins. Dr. Machiela also performs pan-cancer GWAS on adult malignancies in the PLCO study and is developing the DCEG GWAS Explorer as a platform to examine, visualize, and share PLCO GWAS summary statistics across several traits.

Dr. Machiela is the creator of a web-based tool, LDlink, which interactively explores linkage disequilibrium across 1000 Genomes population groups. LDlink is tailored for investigators interested in mapping disease susceptibility loci by generating output linking correlated alleles and highlighting putative functional variants. He is also the creator of AuthorArranger, an online tool that helps researchers and consortia create and format title pages for journal submission.


Dr. Machiela received his M.P.H. in epidemiology from the University of Michigan and his Sc.D. in epidemiology from the Harvard T.H. Chan School of Public Health. His doctoral thesis focused on germline genetics and prostate cancer risk. Dr. Machiela joined the Laboratory of Translational Genomics as a postdoctoral fellow in 2012 and transitioned to the Laboratory of Genetic Susceptibility in 2015. In 2016, he was promoted to research fellow. Dr. Machiela was appointed to the position of Earl Stadtman Tenure-Track Investigator in 2017.

Selected Publications

  1. Machiela MJ, Zhou W, Sampson JN, Dean MC, Jacobs KB, Black A, Brinton LA, Chang IS, Chen C, Chen C, Chen K, Cook LS, Crous Bou M, De Vivo I, Doherty J, Friedenreich CM, Gaudet MM, Haiman CA, Hankinson SE, Hartge P, Henderson BE, Hong YC, Hosgood HD 3rd, Hsiung CA, Hu W, Hunter DJ, Jessop L, Kim HN, Kim YH, Kim YT, Klein R, Kraft P, Lan Q, Lin D, Liu J, Le Marchand L, Liang X, Lissowska J, Lu L, Magliocco AM, Matsuo K, Olson SH, Orlow I, Park JY, Pooler L, Prescott J, Rastogi R, Risch HA, Schumacher F, Seow A, Setiawan VW, Shen H, Sheng X, Shin MH, Shu XO, VanDen Berg D, Wang JC, Wentzensen N, Wong MP, Wu C, Wu T, Wu YL, Xia L, Yang HP, Yang PC, Zheng W, Zhou B, Abnet CC, Albanes D, Aldrich MC, Amos C, Amundadottir LT, Berndt SI, Blot WJ, Bock CH, Bracci PM, Burdett L, Buring JE, Butler MA, Carreón T, Chatterjee N, Chung CC, Cook MB, Cullen M, Davis FG, Ding T, Duell EJ, Epstein CG, Fan JH, Figueroa JD, Fraumeni JF Jr, Freedman ND, Fuchs CS, Gao YT, Gapstur SM, Patiño-Garcia A, Garcia-Closas M, Gaziano JM, Giles GG, Gillanders EM, Giovannucci EL, Goldin L, Goldstein AM, Greene MH, Hallmans G, Harris CC, Henriksson R, Holly EA, Hoover RN, Hu N, Hutchinson A, Jenab M, Johansen C, Khaw KT, Koh WP, Kolonel LN, Kooperberg C, Krogh V, Kurtz RC, LaCroix A, Landgren A, Landi MT, Li D, Liao LM, Malats N, McGlynn KA, McNeill LH, McWilliams RR, Melin BS, Mirabello L, Peplonska B, Peters U, Petersen GM, Prokunina-Olsson L, Purdue M, Qiao YL, Rabe KG, Rajaraman P, Real FX, Riboli E, Rodríguez-Santiago B, Rothman N, Ruder AM, Savage SA, Schwartz AG, Schwartz KL, Sesso HD, Severi G, Silverman DT, Spitz MR, Stevens VL, Stolzenberg-Solomon R, Stram D, Tang ZZ, Taylor PR, Teras LR, Tobias GS, Viswanathan K, Wacholder S, Wang Z, Weinstein SJ, Wheeler W, White E, Wiencke JK, Wolpin BM, Wu X, Wunder JS, Yu K, Zanetti KA, Zeleniuch-Jacquotte A, Ziegler RG, de Andrade M, Barnes KC, Beaty TH, Bierut LJ, Desch KC, Doheny KF, Feenstra B, Ginsburg D, Heit JA, Kang JH, Laurie CA, Li JZ, Lowe WL, Marazita ML, Melbye M, Mirel DB, Murray JC, Nelson SC, Pasquale LR, Rice K, Wiggs JL, Wise A, Tucker M, Pérez-Jurado LA, Laurie CC, Caporaso NE, Yeager M, Chanock SJ. Characterization of large structural genetic mosaicism in human autosomes. Am J Hum Genet. 2015;96(3):487-97.
  2. Lin SH, Brown DW, Machiela MJ. LDtrait: An Online Tool for Identifying Published Phenotype Associations in Linkage Disequilibrium. Cancer Res. 2020;80(16):3443-3446.
  3. Lin SH, Loftfield E, Sampson JN, Zhou W, Yeager M, Freedman ND, Chanock SJ, Machiela MJ. Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men. Sci Rep. 2020;10(1):3655.
  4. Brown DW, Lin SH, Loh PR, Chanock SJ, Savage SA, Machiela MJ. Genetically predicted telomere length is associated with clonal somatic copy number alterations in peripheral leukocytes. PLoS Genet. 2020;16(10):e1009078.

Related Scientific Focus Areas

This page was last updated on Wednesday, January 19, 2022