Christopher Baker

Research Interests

My overall objective is to understand the genetic and molecular regulatory system controlling the location and rate of meiotic recombination, the process that generates new genetic variation in sexually reproducing organisms. Ever since my early exposure to the power of artificial selection in agriculture while working on a vegetable farm in Vermont, I have been curious about the connection between phenotypic and genotypic variation. Genetic recombination is also critical to the successful completion of meiosis, that when aberrant, impacts human fertility and health. However, little is known about the molecular components of the system controlling where recombination occurs. I use genetic, genomic and molecular biology strategies to identify genes regulating the rate at which meiotic hotspots, the physical sites of DNA recombination, are activated. The Paigen lab is one of several groups that recently discovered one such gene, Prdm9, which controls the position of recombination sites in mice and humans.

Selected Publications

• Byers C, Spruce C, Fortin HJ, Hartig EI, Czechanski A, Munger SC, Reinholdt LG, Skelly DA, Baker CL. Genetic control of the pluripotency epigenome determines differentiation bias in mouse embryonic stem cells. EMBO J. 2022 Dec 17; 41(2):e109445
• Skelly DA, Czechanski A, Byers C, Aydin S, Spruce C, Olivier C, Choi K, Gatti DM, Raghupathy N, Keele GR, Stanton A, Vincent M, Dion S, Greenstein I, Pankratz M, Porter DK, Martin W, O’Connor C, Qin W, Harrill AH, Choi T, Churchill GA, Munger SC, Baker CL, Reinholdt LG. Mapping the Effects of Genetic Variation on Chromatin State and Gene Expression Reveals Loci That Control Ground State Pluripotency. Cell Stem Cell. 2020 Sep 3; 27(3):459-469.e8
• Ortmann D, Brown S, Czechanski A, Aydin S, Muraro D, Huang Y, Tomaz RA, Osnato A, Canu G, Wesley BT, Skelly DA, Stegle O, Choi T, Churchill GA, Baker CL, Rugg-Gunn PJ, Munger SC, Reinholdt LG, Vallier L. Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation. Cell Stem Cell. 2020 Sep 3; 27(3):470-481.e6
• Lau KX, Mason EA, Kie J, De Souza DP, Kloehn J, Tull D, McConville MJ, Keniry A, Beck T, Blewitt ME, Ritchie ME, Naik SH, Zalcenstein D, Korn O, Su S, Romero IG, Spruce C, Baker CL, McGarr TC, Wells CA, Pera MF. Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal. Nat Commun. 2020 May 15; 11(1):2420
• Spruce C, Dlamini S, Ananda G, Bronkema N, Tian H, Paigen K, Carter GW, Baker CL. HELLS and PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots. Genes Dev. 2020 Mar 1; 34(5-6):398-412
• Mihola O, Pratto F, Brick K, Linhartova E, Kobets T, Flachs P, Baker CL, Sedlacek R, Paigen K, Petkov PM, Camerini-Otero RD, Trachtulec Z. Histone methyltransferase PRDM9 is not essential for meiosis in male mice. Genome Res. 2019 Jul; 29(7):1078-1086
• Baker CL, Walker M, Arat S, Ananda G, Petkova P, Powers NR, Tian H, Spruce C, Ji B, Rausch D, Choi K, Petkov PM, Carter GW, Paigen K. Tissue-Specific TransRegulation of the Mouse Epigenome. Genetics. 2019 Mar; 211(3):831-845
• Baker CL, Pera MF. Capturing Totipotent Stem Cells. Cell Stem Cell. 2018 Jan 4; 22(1):25-34
• Powers NR, Parvanov ED, Baker CL, Walker M, Petkov PM, Paigen K. The Meiotic Recombination Activator PRDM9 Trimethylates Both H3K36 and H3K4 at Recombination Hotspots In Vivo. PLoS Genet. 2016 Jun; 12(6):e1006146
• Narasimhan VM, Hunt KA, Mason D, Baker CL, Karczewski KJ, Barnes MR, Barnett AH, Bates C, Bellary S, Bockett NA, Giorda K, Griffiths CJ, Hemingway H, Jia Z, Kelly MA, Khawaja HA, Lek M, McCarthy S, McEachan R, O’Donnell-Luria A, Paigen K, Parisinos CA, Sheridan E, Southgate L, Tee L, Thomas M, Xue Y, Schnall-Levin M, Petkov PM, Tyler-Smith C, Maher ER, Trembath RC, MacArthur DG, Wright J, Durbin R, van Heel DA. Health and population effects of rare gene knockouts in adult humans with related parents. Science. 2016 Apr 22; 352(6284):474-7