Hoffmann Group

Our laboratory investigates the role of the DNA damage response and cell cycle proteins in governing the genetic changes that occur in the germline to generate diversity and maintain genome stability.

Research interests

Chromosomes are rearranged and organized into new sets to create diversity as they are passed from parent to offspring through the germline. The genetic changes can be followed in populations, however this represents only a small proportion of the diversity that is generated in our germline. Men produce 500 billion sperm in their lifetime and women are born with two million eggs. Human reproduction is particularly error-prone. 50% of pre-implantation embryos have defects in their development and 20%-85% of human eggs have extra or missing chromosomes (aneuploidy). Maternal age is the strongest risk factor known for aneuploidy and our interests in reproductive aging also includes understanding the decreased quality as well as the decline in the number of eggs as women age.

Our laboratory investigates the role of the DNA damage response and cell cycle proteins in governing the genetic changes that occur in the germline to generate diversity and maintain genome stability. In particular, we focus on those genes that when defective give to reproductive disease or cancer. We use a powerful combination of model organisms (mouse and yeast) as well as human eggs and embryos to explore this poorly understood area of human biology.

Publications

Full publications, see https://orcid.org/0000-0002-2588-0652

Cannavo E, Sanchez A, Anand R, Ranjha L, Hugener J, Adam C, Acharya A, Weyland N, Aran-Guiu X, Charbonnier JB, Hoffmann ER, Borde V, Matos J, Cejka P. Regulation of the MLH1-MLH3 endonuclease in meiosis. Nature. 2020 Aug 19.
Sankar A, Lerdrup M, Manaf A, Johansen JV, Martin Gonzalez J, Borup R, Blanshard R, Klungland A, Hansen K., Andersen CY, Dahl JA, Helin K, Hoffman ER KDM4A regulates the maternal-to-zygotic transition by protecting broad H3K4me3 domains from H3K9me3 invasion in oocytes. Nat Cell Biol (March 2020).
Girardi L, Serdarogullari M, Patassini C, Poli M, Fabiani M, Caroselli S, Coban O, Findikli N, Boynukalin FK, Bahceci M, Chopra R, Canipari R, Cimadomo D, Rienzi L, Ubaldi F, Hoffmann E, Rubio C, Simon C, Capalbo A. I ncidence, Origi n, and Predictive Model f or the Detection and Clinical Management of Segmental Aneuploidies in Human Embry os. Am J Hum Genet. 2020 Mar 19.
Abildgaard AB, Stein A, Nielsen SV, Schultz-Knudsen K, Papaleo E, Shrikhande A, Hoffmann ER, Bernstein I, Gerdes AM, Takahashi M, Ishioka C, Lindorff-Larsen K, Hartmann-Petersen R. Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome. eLife. 2019 Nov 7;8. pii: e49138.
Dong L, Kristensen SG, Hildorf S, Gul M, Clasen-Linde E, Fedder J, Hoffmann ER, Cortes D, Thorup J, Andersen CY.
Propagation of Spermatogonial Stem Cell-Like Cells From Infant Boys. Front Physiol. 2019 Sep 19;10:1155.
Zielinska AP, Bellou E, Sharma N, Frombach AS, Seres B, Gruhn JR, Blayney M, Eckel H, Moltrecht R, Elder K, Hoffmann ER, Schuh M Meiotic Kinetochores Fragment into Multiple Lobes upon Cohesin Loss in Aging Eggs Current Biology 29, 1–17.e1–e7, November 18, 2019
Gruhn JR, Zielinska AP, Shukla V, Blanshard R, Capalbo A, Cimadomo D, Nikiforov D, Chan AC, Newnham LJ, Vogel I, Scarica C, Krapchev M, Taylor D, Kristensen SG, Cheng J, Ernst E, Bjørn AB, Colmorn LB, Blayney M, Elder K, Liss J, Hartshorne G, Grøndahl ML, Rienzi L, Ubaldi F, McCoy R, Lukaszuk K, Andersen CY, Schuh M, Hoffmann ER. Chromosome errors in human eggs shape natural fertility over reproductive life span. Science. 2019 Sep 27;365(6460):1466-1469.