Biochemistry Department - Primary Faculty
Saba Valadkhan, M.D., Ph.D.
- Columbia University, New York City
Research in our lab is focused on the role of long non-coding RNAs in higher eukaryotes. Large scale analyses of transcriptional output of the eukaryotic genomes have revealed the existence of a very large number of long non-coding transcripts. While the majority of them remain unstudied, current evidence suggest that the study of these mysterious transcripts is likely to provide answers to many remaining questions in biology of higher eukaryotes.
Using examples of mouse and human long non-coding RNAs as study models, we focus on in-depth analysis of their role in a number of fundamental biological processes:
1) Long non-coding RNAs in neurogenesis
We have shown that the expression of a long non-coding RNA is required for physiological neuronal differentiation. Interestingly, we could also show that forced ectopic expression of this RNA in myoblasts and fibroblasts leads to their reprogramming into neurons. Currently active projects in the lab address the mechanism of this intriguing observation and potential implications in regenerative medicine.
2) The role of long non-coding RNAs in neurodegenerative diseases
Another active project in the lab is based on our observation that a long non-coding RNA plays a major role in regulating the magnitude of the canonical stress response pathway. Considering the critical role of the stress response pathway in neurodegenerative diseases, we are in the process of defining the role of our RNA in neurodegenerative processes and its potential as a therapeutic measure.
3) Long non-coding RNAs and cancer
We have shown that the expression of a long non-coding RNA is progressively increased as breast and lung cancer cells acquire invasive and metastatic properties. We are in the process of defining the interactions of this RNA with the cellular pathways active in cancer, in addition to in vivo studies in the mouse to define the impact of altering the expression of this RNA on tumor progression.
- Kambara H., Niazi F., Kostadinova L., Moonka D. K., Siegel C. T., Post A. B., Carnero E., Barriocanal M., Fortes P., Anthony D. D., and Valadkhan S.
“Negative regulation of the interferon response by an interferon-induced long non-coding RNA”
Nucleic Acids Res 42 (16): 10668-80 (2014).
- Zhang B., Gunawardane L., Niazi F., Jahanbani F., Chen X., and Valadkhan S.
“A novel RNA motif mediates the strict nuclear localization of a long noncoding RNA”
Mol Cell Biol 34 (12): 2318-29 (2014). Read article in PubMedCentral
- Valadkhan S.
“The role of snRNAs in spliceosomal catalysis”
Prog Mol Biol Transl Sci 120: 195-228 (2013).
- Valadkhan S. and Gunawardane L. S.
“Role of small nuclear RNAs in eukaryotic gene expression”
Essays Biochem 54: 79-90 (2013).
- Niazi F. and Valadkhan S.
“Computational analysis of functional long noncoding RNAs reveals lack of peptide-coding capacity and parallels with 3' UTRs”
RNA 18 (4): 825-43 (2012). Read article in PubMedCentral
- Valadkhan S.
“A snRNP's ordered path to maturity”
Genes Dev 25 (15): 1563-7 (2011). Read article in PubMedCentral
- Jaladat Y., Zhang B., Mohammadi A., and Valadkhan S.
“Splicing of an intervening sequence by protein-free human snRNAs”
RNA Biol 8 (3): 372-7 (2011). Read article in PubMedCentral
- Valadkhan S. and Jaladat Y.
“The spliceosomal proteome: at the heart of the largest cellular ribonucleoprotein machine”
Proteomics 10 (22): 4128-41 (2010).
- Lee C., Jaladat Y., Mohammadi A., Sharifi A., Geisler S., and Valadkhan S.
“Metal binding and substrate positioning by evolutionarily invariant U6 sequences in catalytically active protein-free snRNAs”
RNA 16 (11): 2226-38 (2010). Read article in PubMedCentral
- Valadkhan S.
“Role of the snRNAs in spliceosomal active site”
RNA Biol 7 (3): 345-53 (2010).
- Valadkhan S. and Nilsen T. W.
“Reprogramming of the non-coding transcriptome during brain development”
J Biol 9 (1): 5 (2010). Read article in PubMedCentral
- Valadkhan S., Mohammadi A., Jaladat Y., and Geisler S.
“Protein-free small nuclear RNAs catalyze a two-step splicing reaction”
Proc Natl Acad Sci U S A 106 (29): 11901-6 (2009). Read article in PubMedCentral
- Valadkhan S. and Manley J. L.
“The use of simple model systems to study spliceosomal catalysis”
RNA 15 (1): 4-7 (2009). Read article in PubMedCentral