Chowdhury, Tamjid, PhD

Tamjid Chowdhury, PhD

Tamjid Chowdhury, PhD

Postdoc Fellow – Dr. Ramani Ramchandran’s Lab

(414) 955-2557

Research

“Temporal and spatial post-transcriptional regulation of zebrafish tie1 mRNA by long non-coding RNA”

Presentation
3rd Zebrafish For Personalized/Precision Medicine Conference in Toronto, Canada, September 27-29, 2017

“Temporal and spatial post-transcriptional regulation of zebrafish tie1 mRNA by long non-coding RNA”

Long non-coding RNAs have been established as a major class of RNA that regulates development. In 2010, the Ramchandran lab identified long non-coding RNAs (lncRNAs) from the Tyrosine kinase containing Immunoglobulin and Epidermal growth factor homology-1(tie1) locus in zebrafish, humans and mice. These lncRNAs are transcribed in the opposite orientation to the protein coding transcript (mRNAs) that originate from the tie1 locus. Thus, they are referred to as tie1 anti-sense (tie1AS) lncRNAs. The Ramchandran lab further showed that one of the three TIE1AS lncRNAs identified in humans and one of the two tie1AS lncRNAs identified in zebrafish can regulate tie1/TIE1 mRNA levels. Given that Tie1 gene is an essential gene and TIE1 protein is critical for angiogenesis, therefore, the identification of tie1AS/TIE1AS mediated regulation of tie1/TIE1 gene is a significant finding. My project is focused on identifying the mechanism used by the tie1AS/TIE1AS lncRNA to regulate tie1/TIE1 mRNA.

In zebrafish embryos, I have shown that tie1AS interacts with a well-known RNA binding protein called Embryonic lethal and abnormal vision Drosophila-like1 (Elavl1). This interaction takes place only in the head at a very specific time (between 26 – 31 hours post fertilization). Disturbing the interaction between tie1AS and Elavl1 through the use of morpholino antisense oligonucleotides (MOs), photoactivatable MOs resulted in elevated tie1 mRNA levels in the head between 26 – 31 hours post fertilization (hpf). Similar results were obtained with CRISPR mediated downregulation of tie1AS levels. The elevated tie1 mRNA levels coincided with reduced eye-sizes, reduced ventricular spaces, and dilated primary blood vessels. Thus, my results show that the interaction between tie1AS and Elavl1 forms a complex that is responsible for downregulating tie1 mRNA levels in a temporal and spatial manner. My most recent findings show that human TIE1AS that was previously shown to regulate TIE1 mRNA levels interacts with the Elavl1 orthologue in humans, HuR. I am currently focused on characterizing this interaction in human endothelial cells and studying the functional relevance of this interaction.

Lab

Ramchandran Lab

Ramchandran Lab

Dr. Ramchandran’s lab is involved in gynecologic cancer research with a specific focus on the role of metabolism in gynecological cancer. Dr. Ramchandran…

Read More ›