Swathi Arur
Professor
The University of Texas MD Anderson Cancer Center
Department of Genetics
We use multidisciplinary approaches and model systems with a goal to gain knowledge into three specific biological questions. We hope to understand the basis of (i) environmental signaling and its role in male and female fertility, (ii) signaling and control of birth defects, with a specific focus on the Ras pathway and (iii) signaling based control of post-transcriptional regulation on cancer metastasis. Below, I provide highlights of some of our ongoing research. I. Nutritional programs that govern female germ cell development and transition to embryo development. Female meiosis I is completed in utero in vertebrates. Defects in meiosis I during female germ cell development manifest as sterility in later in her life, or as birth defects in her children. While we assume that maternal health and nutrition influences progeny health, we just never knew that maternal nutritional status regulates female child’s germ cell health as well, until our lab discovered a direct link between maternal nutrition and regulation of female meiosis I and oocyte development. Trainee publications: Lopez and Chen et al., Developmental Cell, 2013; Suen et al., Nat Str Mol Biol, 2013; Mattingly et al., J Biophy, 2015; Das et al., Science Advances 2020; Das et al., PNAS, 2022; Trimmer et al., Cell Reports, 2023. II. Small RNA pathways that control development: We discovered a direct intersection between environmentally activated signaling pathways and production of small RNAs that controls oocyte development, and oocyte to embryo transition. The discoveries include understanding the role of Dicer and Drosha phosphorylation, small RNA production, and determining why subsets of populations of small RNAs are generated, and what this may mean. Trainee publications: Drake et al., Developmental Cell, 2014; Minogue et al., Nat Comm, 2018; Minogue et al., Current Protocols, 2019; Aryal et al., 2018, PNAS. III. Dicer phosphorylation and nuclear role in cancer development: We discovered that Dicer is phoshorylated and translocated to the nucleus in C. elegans. We then generated mouse models to determine its role in cancer development. Phosphorylated nuclear Dicer drives tumor spread in mouse models of oncogenic KRas and mutant p53. We then discovered in non-small cell lung cancers that phosphorylated nuclear Dicer does not regulate microRNAs, instead it forms a large chromatin complex in the nucleus which helps open chromatin and affect transcription of lineage defining genes resulting in lineage reprogramming of lung tumor cells to gastric lineage. Trainee publications: Aryal et al., 2018, Cancer Res; Reyes et al., 2023, Science Advances.
Education & Training
Ph.D. - All India Institute for Medical Sciences - 2002
Research Info
regulation and execution of RAS-ERK signaling; germ cell development; C. elegans genetics