Ph.D., Brunel University
Office Phone: (216) 687-2395
Lab Phone: (216) 523-7422
COSHP Faculty Profile
Dr. Shukla is an Associate Professor of Biology. He received his B.S. in Chemistry from Delhi University and Ph.D. in Molecular Biology and Biochemistry from Brunel University, London, in 1997. He has been a faculty member of Cleveland State University since 2006.
My research goal is to better understand molecular mechanisms that control eukaryotic gene expression at the RNA level. Within this framework, I am exploring three issues: (1) noncoding RNAs and their roles in gene expression, (2) nuclear pre-mRNA splicing, and finally, (3) specific RNA:RNA and RNA:Protein interactions. The current emphasis of the lab is on miRNA-mediated regulation of human androgen receptor expression. Androgen receptor is a key modulator that has been implicated in hormonal dependent and independent stages of prostate cancer. Based on computational predictions and phylogenetic analysis I have proposed a miRNA-mediated model of Androgen Receptor regulation. One particularly interesting idea that I would like to investigate further is the critical level of Androgen receptor influences the transition from the hormone-dependent to hormone refractory stage of prostate cancer. Using computational biology tools I have identified a number of miRNAs that have the potential to interact with the 3' untranslated region of the receptor mRNA. This observation gives rise to the hypothesis that androgen receptor expression is tightly regulated by combinatorial control of miRNAs and deregulation of these miRNAs may contribute in the progression of prostate cancer. Using lentiviral expression systems we are overexpressing a number of miRNAs to understand how androgen receptor expression is controlled by these miRNAs in a variety of prostatic carcinoma cells.
The research in my laboratory is also aimed at understanding the nuclear pre-mRNA splicing by using in vitro and in vivo methods. We are currently studying the structure-function of several snRNAs of the minor spliceosome including U11, U12, U4atac and U6atac. Recently we have identified a small RNA element in the U6atac snRNA that functions in the 'guiding' of the specific spliceosomal complexes to the minor class splice sites. We are now pursuing the identification of proteins that may interact with these U6atac snRNA sub-structures to further define their role in the splicing of minor class introns. We are also studying specific RNA-RNA base-pairing interaction involved in the splicing of the minor class intron using biochemical and in vivo genetic approaches. These studies will help us to understand how multiple sequentially interacting snRNAs facilitate the removal of introns from the precursor mRNA of genes.
1: Sikand K, Singh J, Ebron JS, Shukla GC. Housekeeping gene selection advisory: glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin are targets of miR-644a. PLoS One. 2012;7(10):e47510. doi: 10.1371/journal.pone.0047510. Epub 2012 Oct 16. PubMed PMID: 23091630; PubMed Central PMCID: PMC3472982.
2: Sikand K, Shukla GC. Functionally important structural elements of U12 snRNA. Nucleic Acids Res. 2011 Oct;39(19):8531-43. doi: 10.1093/nar/gkr530. Epub 2011 Jul 6. PubMed PMID: 21737423; PubMed Central PMCID: PMC3201867.
3: Sikand K, Slaibi JE, Singh R, Slane SD, Shukla GC. miR 488* inhibits androgen receptor expression in prostate carcinoma cells. Int J Cancer. 2011 Aug 15;129(4):810-9. doi: 10.1002/ijc.25753. PubMed PMID: 21710544.
4: Shukla GC, Haque F, Tor Y, Wilhelmsson LM, Toulmé JJ, Isambert H, Guo P, Rossi JJ, Tenenbaum SA, Shapiro BA. A boost for the emerging field of RNA nanotechnology. ACS Nano. 2011 May 24;5(5):3405-18. doi: 10.1021/nn200989r. PubMed PMID: 21604810; PubMed Central PMCID: PMC3102291.
5: Sikand K, Barik S, Shukla GC. MicroRNAs and Androgen Receptor 3' Untranslated Region: A Missing Link in Castration-resistant Prostate Cancer? Mol Cell Pharmacol. 2011;3(3):107-113. PubMed PMID: 22468168; PubMed Central PMCID: PMC3315684.
6: Shukla GC, Singh J, Barik S. MicroRNAs: Processing, Maturation, Target Recognition and Regulatory Functions. Mol Cell Pharmacol. 2011;3(3):83-92. PubMed PMID: 22468167; PubMed Central PMCID: PMC3315687.
7: Sikand K, Slane SD, Shukla GC. Intrinsic expression of host genes and intronic miRNAs in prostate carcinoma cells. Cancer Cell Int. 2009 Aug 12;9:21. doi: 10.1186/1475-2867-9-21. PubMed PMID: 19674469; PubMed Central PMCID: PMC2739157.
8: Dietrich RC, Padgett RA, Shukla GC. The conserved 3' end domain of U6atac snRNA can direct U6 snRNA to the minor spliceosome. RNA. 2009 Jun;15(6):1198-207. doi: 10.1261/rna.1505709. Epub 2009 Apr 16. PubMed PMID: 19372536; PubMed Central
9: Shukla GC, Padgett RA. U4 small nuclear RNA can function in both the major and minor spliceosomes. Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):93-8. Epub 2003 Dec 22. PubMed PMID: 14691257; PubMed Central PMCID: PMC314144.
10: Shukla GC, Cole AJ, Dietrich RC, Padgett RA. Domains of human U4atac snRNA required for U12-dependent splicing in vivo. Nucleic Acids Res. 2002 Nov 1;30(21):4650-7. PubMed PMID: 12409455; PubMed Central PMCID: PMC135832.
11: Shukla GC, Padgett RA. A catalytically active group II intron domain 5 can function in the U12-dependent spliceosome. Mol Cell. 2002 May;9(5):1145-50. PubMed PMID: 12049749.
12: Padgett RA, Shukla GC. A revised model for U4atac/U6atac snRNA base pairing. RNA. 2002 Feb;8(2):125-8. PubMed PMID: 11911359; PubMed Central PMCID: PMC1370236.
13: Dietrich RC, Shukla GC, Fuller JD, Padgett RA. Alternative splicing of U12-dependent introns in vivo responds to purine-rich enhancers. RNA. 2001 Oct;7(10):1378-88. PubMed PMID: 11680842; PubMed Central PMCID: PMC1370181.