Throughout my career, I have explored the spectrum of common, complex, and rare human disorders and helped to pioneer the development of new approaches and tools that have become widely applied in human genetics. My current work is focused on large-scale sequencing for precision medicine and on the development and application of robust approaches for calling challenging regions of the genome that are medically important.
In the last decade, my group has applied massively parallel sequencing to hundreds of thousands of samples for multiple large-scale, national genomics programs including the All of Us Research Program, the Centers for Mendelian Genomics, the Trans-Omics for Precision Medicine (TOPMed) program, and the Brotman Baty Institute for Precision Medicine.
We are currently pursuing projects focused on pharmacogenetics, blood typing, and rare and common disease genetics. Two of our projects involve the development of new bioinformatics tools that translate genomic data into clinical outcomes used to predict drug responses, or call blood group alleles for transfusion medicine. We are especially interested in complex loci that are highly polymorphic in human populations. Many of these have hundreds of clinically important haplotypes composed of single nucleotide variants (SNVs), small insertion-deletions (indels), and/or large structural variants (SVs). Translating these sequence variants from genomic coordinates into meaningful clinical interpretations is an important area of research that will continue to take center stage as personalized genetics scale through programs such as TOPMed and All of Us. We also continue to collaborate with investigators working in Mendelian genetics, and we have a number of ongoing projects on pediatric and adult disorders.
De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population. Kessler MD, Loesch DP, Perry JA, Heard-Costa NL, Taliun D, Cade BE, Wang H, Daya M, Ziniti J, Datta S, Celedón JC, Soto-Quiros ME, Avila L, Weiss ST, Barnes K, Redline SS, Vasan RS, Johnson AD, Mathias RA, Hernandez R, Wilson JG, Nickerson DA, Abecasis G, Browning SR, Zöllner S, O'Connell JR, Mitchell BD; National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium; TOPMed Population Genetics Working Group, O'Connor TD. Proc Natl Acad Sci U S A. 2020 Feb 4;117(5):2560-2569.
Interrogation of CYP2D6 Structural Variant Alleles Improves the Correlation Between CYP2D6 Genotype and CYP2D6-Mediated Metabolic Activity. Dalton R, Lee SB, Claw KG, Prasad B, Phillips BR, Shen DD, Wong LH, Fade M, McDonald MG, Dunham MJ, Fowler DM, Rettie AE, Schuetz E, Thornton TA, Nickerson DA, Gaedigk A, Thummel KE, Woodahl EL. Clin Transl Sci. 2020 Jan;13(1):147-156.
The pleiotropy associated with de novo variants in CHD4, CNOT3, and SETD5 extends to moyamoya angiopathy. Pinard A, Guey S, Guo D, Cecchi AC, Kharas N, Wallace S, Regalado ES, Hostetler EM, Sharrief AZ, Bergametti F, Kossorotoff M, Hervé D, Kraemer M, Bamshad MJ, Nickerson DA, Smith ER, Tournier-Lasserve E, Milewicz DM. Genet Med. 2020 Feb;22(2):427-431.
Calling Star Alleles with Stargazer in 28 Pharmacogenes with Whole Genome Sequences. Lee SB, Wheeler MM, Thummel KE, Nickerson DA. Clin Pharmacol Ther. 2019 Dec;106(6):1328-1337.
Discovery of common and rare genetic risk variants for colorectal cancer. Huyghe JR, Bien SA, Harrison TA, Kang HM, Chen S, Schmit SL, et.al. Nat Genet. 2019 Jan;51(1):76-87.
Genomic characterization of the RH locus detects complex and novel structural variation in multi-ethnic cohorts. Wheeler MM, Lannert KW, Huston H, Fletcher SN, Harris S, Teramura G, Maki HJ, Frazar C, Underwood JG, Shaffer T, Correa A, Delaney M, Reiner AP, Wilson JG, Nickerson DA, Johnsen JM; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium. Genet Med. 2019 Feb;21(2):477-486.