Vahid Khoddami Ph.D.
Department of Stem Cells and Developmental Biology
Vahid Khoddami got his BSc degree in Medical Laboratory Sciences from Tehran University of Medical Sciences (Iran) and his MSc degree in Medical Biotechnology from Tarbiat Modares Univesity (Iran). In his MSc he worked on implementation of RNAi in cancer cells. In 2007 he moved to United States for graduate school and got his PhD degree in Molecular Biology from University of Utah (USA) in 2013. After PhD he spent another year in Utah serving as Postdoctoral fellow at Huntsman Cancer Institute. In his PhD and postdoc in Utah, under the supervision of Prof. Bradley cairns (HHMI investigator) he worked on developing novel technologies for Transcriptome-wide profiling of nucleotide modifications in RNA. In 2014, for his work on pioneering the Transcriptome-wide mapping of modified nucleotides, Vahid khoddami received the “Annual James W. Prahl Memorial Award” for the Outstanding Graduate Student in Biological or Biomedical Sciences at University of Utah School of Medicine. In the same year; 2014, he moved to Boston to start his second postdoc at Harvard Medical School in the department of Cell Biology under the supervision of Prof. Danesh Moazed (HHMI investigator) working on some interesting aspects of RNA and also heterochromatin biology in yeast systems; saccharomyces cerevisiae and schizosaccharomyces pombe. In the fall of 2017, after 10 years of education and research in US, he returned back to Iran and joined Royan Institute as an assistant professor to work on both basic (particularly RNA epitranscriptome) and clinical (especially RNA-based therapeutics) aspects of the RNA world.
A) RNA “epitranscriptome” in Health and Disease
Post-transcriptional modification of RNA is common, but RNA modifications are far more diverse than DNA or protein modifications, with >110 distinct natural nucleotide modifications isolated so far. From the discovery of the first modified ribonucleotide (~60 years ago), our knowledge of RNA modifications has been focused on abundant tRNAs and rRNAs. Recent studies; however, suggest a more widespread distribution of the few RNA modifications that have been tested transcriptome-wide. Despite extensive studies on the structural and functional impact of several modifications on tRNAs, rRNAs, and snRNAs in the past, revealing interesting clues about their functions, the role of many modifications, especially those in mRNAs, has remained elusive. With recent transcriptome-wide studies reporting hundreds of modified mRNAs, many research groups have begun to study the impact of modifications collectively on all candidate RNAs together, revealing some hints. However, a true functional analysis is hampered by such collective analysis as it can mask the behavior of individual molecules in the pool, overlook the direct vs. indirect effects, and suffers from false positives and negatives (which are not uncommon in those initial reports). In our group at Royan Institute we are concentrating on few high-confidence and validated modified sites in some critical RNAs for a focused functional analysis to understand the consequences of RNA nucleotide modifications.
B) RNA therapeutics
The “central dogma of biology”; DNA->RNA->Protein, is similarly central in medicine. Gene therapy based technologies and recombinant-protein therapeutics have targeted the DNA and Protein ends of the central dogma, especially the latter has provided effective therapies for a number of refractory diseases. Regarding the middle part; the RNA, in addition to the development of siRNA-based strategies for targeted disruption of aberrant transcripts, application of in-vitro transcribed (IVT) mRNAs for expression of especial proteins inside the cells has recently raised wide attention. IVT-mRNA, is a new class of drugs, with: I) a simple universal production procedure for all mRNAs at relatively low cost, II) transient expression with no integration into the genome, and III) wide-range of applications from protein-replacement and vaccination against pathogens, to IVT-mRNA-based cancer-immunotherapy by CAR-T-Cells, CRISPR-mediated gene editing, genetic reprogramming of stem cells, and tissue engineering. In our group at Royan Institute we are working on optimization of available and development of new reagents to provide effective RNA therapeutics with potential applications in prevention and treatment of multiple diseases, and RNA-based programming and reprogramming cocktails with applications in regenerative medicine.
Niloufar Yousefi, MSc student
Project: Studying the impact of cytosine methylation on mRNA of tumor suppressor genes.
Sara Afshar Aalam, MSc student
Project: Gene therapy of Junctional Epidermolysis bullosa (a collaborative project with Dr. Mohsen Basiri and Dr. Parvaneh Mohamadi groups at Royan Institute).
Niloufar Sehat, PhD student
Project: Development of reagents to provide effective RNA therapeutics with potential applications in prevention and treatment of multiple diseases.
Neda Minaei, PhD student
Project: Development of RNA-based programming and reprogramming cocktails with applications in regenerative medicine.
- Dehghanizadeh, S., Khoddami, V., Mosbruger, T.L., Hammoud, S.S., Edes, K., Berry, T.S., Done, M., Samowitz, W.S., DiSario, J.A., Luba, D.G., Burt, R.W., & Jones, D.A. Active BRAF-V600E is the key player in generation of a sessile serrated polyp-specific DNA methylation profile. PlosOne, In press (2018).
- Khoddami, V., Yerra, A. & Cairns, B.R. Experimental Approaches for Target Profiling of RNA Cytosine Methyltransferases. Methods in Enzymology, 560, 273-96 (2015).
- Shakya, A., Callister, C., Goren, A., Yosef, N., Garg, N., Khoddami, V., Nix, D., Regev, A., and Tantin, D. (2015). Pluripotency transcription factor oct4 mediates stepwise nucleosome demethylation and depletion. Molecular and Cellular Biology, 35, 1014-1025.
- Khoddami V., Cairns B.R. Transcriptome-wide target profiling of RNA cytosine methyltransferases using the mechanism-based enrichment procedure Aza-IP. Nature Protocols, 2014. 9(2): p. 337-61.
- Khoddami V., Cairns B.R. Identification of direct targets and modified bases of RNA cytosine methyltransferases. (2013) Nature Biotechnology, 31 (5), pp. 458-464.
We are accepting MSc or PhD students who are interested to join us for working on either of RNA modifications or RNA therapeutics.