Harvard Catalyst Profiles

Research Assistant/Student positions available at Massachusetts General Hospital Cancer Center (Simches Building, Boston) in a lab working on non-coding RNAs and microRNAs and their roles/mechanisms in cancers and development using cancer cell lines, stem cells and Xenopus oocytes.

My research program aims to investigate the mechanisms of gene expression control of critical genes by non-coding RNAs, microRNAs and RNA-protein complexes (RNPs), their regulation and interconnections in response to quiescent and hypoxic conditions in tumors, stem cells and germ cells. Quiescent (G0) cells include an assortment of reversibly-arrested cells, including dormant stem cells. G0 cancer cells resist clinical therapy and prevent irreversible arrest, while maintaining the ability to re-enter the cell cycle, thus eventually leading to cancer chemoresistance and recurrence. G0 demonstrates a switch to a distinct gene expression program where post-transcriptional changes, including mRNA untranslated region (UTR) elements such as AU-rich elements (AREs), altered RNPs, non-coding RNAs and microRNAs contribute to the maintenance of this state. AREs are highly conserved mRNA 3'-UTR regulatory elements while microRNAs are small non-coding RNAs that target distinct UTR sites and control post-transcriptional gene expression of clinically relevant messages; their deregulation leads to a broad range of critical effects such as tumor progression, immune and developmental disorders.

The primary goal of our research program is to investigate non-coding RNA, microRNA- and RNA binding protein-controlled expression of critical genes; in particular, of clinically relevant mRNAs that lead to tumor progression and maintain quiescent cells in cancers and thereby, resistance and recurrence. An interconnected direction of our research is to investigate ARE and microRNP regulation in cancers and development, specifically, in response to quiescent conditions in tumor cell lines, stem cells and in Xenopus laevis germ cells (oocytes). There are four core directions:

1. To functionally characterize microRNAs and specific non-coding regulatory RNAs, their associated cofactors and target mRNAs that control essential cell state regulators using previously developed in vivo crosslinking coupled affinity purification methods and confirmatory assays

2. To investigate the mechanism of gene expression in distinct cellular conditions and the interconnections between AREs and microRNPs

3. To elucidate the regulation of expression and function of microRNAs and AREs by specific cellular conditions

4. To develop antisense manipulations of selective interactions between regulatory RNAs and their mRNA targets as specific therapeutic approaches to interfere with gene expression essential for the cancer G0 cell state and thereby, abrogate resistant G0 cells in cancer.

These studies should provide a greater understanding of the versatile roles of regulatory non-coding RNAs in cancers and development and lead to novel approaches in small RNA-based therapeutic applications.