Ph.D. Bioinformatics, Zhejiang University, Hangzhou, China

The overarching goal of the lab is to understand the mechanism and function of programmed DNA elimination, a unique form of DNA loss, chromosome end remodeling, and gene silencing. Genome integrity and its maintenance are essential to an organism. Although genome changes can enable variation, flexibility, and evolution, large-scale genome changes, such as chromosome breaks and DNA loss are often detrimental to organisms and lead to diseases, including cancer. However, there are exceptions in nature to this genome constancy rule. In a few organisms, including some parasitic nematodes (intestinal worms) and copepods (small crustaceans), regulated chromosome breaks and DNA loss is a physiological process during early development. This large-scale DNA loss is known as programmed DNA elimination. DNA elimination occurs only in somatic cells, not the germline, leading to a smaller somatic genome. Our previous studies demonstrated that in the nematode Ascaris, ~1,000 germline-expressed genes are lost during DNA elimination, suggesting that DNA elimination is a novel form of gene silencing in somatic cells.

Our lab is using biochemistry, genomics and bioinformatics, cellular and molecular biology tools to study this fundamental biological process that occurs in a broad spectrum of invertebrates and vertebrates. Using the nematode Ascaris and copepod Mesocyclops edax as model systems, we are trying to address outstanding questions related to DNA elimination, including 1). How are the break sites recognized and defined? 2). How are the DNA double-stranded breaks made? 3). How are the DNA break ends processed and repaired? and 4). How is the eliminated DNA degraded? DNA break and repair mechanisms are essential to genome stability and maintenance. Understanding the physiological process of the DNA elimination may provide novel insights into DNA break and repair mechanisms that may facilitate a better understanding of DNA break and loss in diseases.

The parasitic nematode Ascaris remains a significant health problem in many parts of the world, infecting close to a billion people, many of them children, leading to significant morbidity. The related dog/cat parasitic nematode Toxocara, causing human toxocariasis, also is increasingly being recognized as a significant public health problem in the United States. Our genomics and molecular studies on these parasites will also provide new information and insights into parasitic nematode chromosomes and chromatin organization, RNA transcription, DNA replication, DNA breaks and telomere healing. Insights into these biological processes may identify novel molecular processes that could be potential drug targets in parasitic nematodes.

1. Wang J*, Veronezi GMB, Kang Y, Zagoskin M, O’Toole ET, Davis RE*: Comprehensive Chromosome End Remodeling during Programmed DNA Elimination. Current Biology 2020;30(17):3397-3413 (*Corresponding authors).
2. Wang J, Davis RE: Ascaris, Current Biology 2020; 30 R423-R425.
3. Wang J*, Gao S, Mostovoy Y, Kang Y, Zagoskin M, Sun Y, Zhang B, White LK, Easton A, Nutman TB, Kwok PY, Hu S, Nielsen MK, Davis RE*: Comparative Genome Analysis of Programmed DNA Elimination in Nematodes. Genome Research 2017, 27:2001-14 (*Corresponding authors).
4. Kang Y*, Wang J*, Neff A, Kratzer S, Kimura H and Davis RE. Differential Chromosomal Localization of Centromeric Histone CENP-A Contributes to Nematode Programmed DNA Elimination. Cell Reports, 2016, 16: 2308-2316 (*Co-first authors).
5. Wang J*, Garrey J*, Davis RE: Transcription in pronuclei and one- to four-cell embryos drives early development in a nematode. Current Biology 2014, 24:124-133. (*Co-first authors).
6. Wang J*, Davis RE*: Programmed DNA elimination in multicellular organisms. Current Opinion in Genetics & Development 2014, 27:26-34. (*Corresponding authors)
7. Wang J, Mitreva M, Berriman M, Thorne A, Magrini V, Koutsovoulos G, Kumar S, Blaxter ML, Davis RE: Silencing of germline-expressed genes by DNA elimination in somatic cells. Developmental Cell 2012, 23:1072-1080.
8. Wang J, Czech B, Crunk A, Wallace A, Mitreva M, Hannon GJ, Davis RE: Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles. Genome Research 2011, 21:1462-1477.