Research in my laboratory is focused toward understanding the molecular mechanism of regulation of gene expression in prostate and breast cancer, specifically, components of signaling pathways that are involved in cell cycle regulation, progression of metastasis and development of drug resistance. One of the major challenges for treatment of aggressive prostate cancer is development of resistance to chemotherapeutic agents and hormone ablation therapy. We are conducting research on the role of microRNAs on regulation of gene expression and development of resistance to therapies. Our research led to identification of a signature set of microRNAs for detection of aggressive and drug resistant cancers. Additionally, we are determining the mechanism of altered responsiveness to the agents that are involved in induction of mitotic arrest and apoptosis. Our research is directed towards determining the functional roles of cell cycle regulatory proteins, kinases and proteinases on cell cycle progression and turnover of tumor microenvironment. Our studies indicated that DNA replication licensing protein Cdc6 is hormonally regulated and its expression profile could be used as a diagnostic marker for progression and metastasis of prostate cancer. Our studies also identified a functional link between expression of a cytoskeleton regulatory protein and promotion of invasion and metastasis. We are also conducting high throughput screening of compound libraries for identifying novel anticancer agents. Furthermore, we are conducting collaborative research on optimization of uniquely fabricated multifunctional biodegradable polymer particles for cell-specific binding and delivery of therapeutics specifically to cancer cells, and separation of cancer cells from normal cells. Our collaborative research also includes studies on the function of kinases and their native substrates in regulation of cell cycle progression through reversible protein phosphorylation in protozoan parasites.
Recent Publications & Patents
1. Ganapathy K, Ngo C, Andl T, Coppola D, Park J, Chakrabarti R. Anticancer function of microRNA-30e is mediated by negative regulation of HELLPAR, a noncoding macroRNA, and genes involved in ubiquitination and cell cycle progression in prostate cancer. Mol Oncol. 2022 May 25;. doi: 10.1002/1878-0261.13255. [Epub ahead of print] PubMed PMID: 35612714.
2. Berglund A, Matta J, Encarnación-Medina J, Ortiz-Sanchéz C, Dutil J, Linares R, Marcial J, Abreu-Takemura C, Moreno N, Putney R, Chakrabarti R, Lin HY, Yamoah K, Osterman CD, Wang L, Dhillon J, Kim Y, Kim SJ, Ruiz-Deya G, Park JY. Dysregulation of DNA Methylation and Epigenetic Clocks in Prostate Cancer among Puerto Rican Men. Biomolecules. 2021 Dec 21;12(1). doi: 10.3390/biom12010002. PubMed PMID: 35053153; PubMed Central PMCID: PMC8773891.
3. Hasan MF, Ganapathy K, Sun J, Khatib A, Andl T, Soulakova JN, Coppola D, Zhang W, Chakrabarti R. LncRNA PAINT is associated with aggressive prostate cancer and dysregulation of cancer hallmark genes. Int J Cancer. 2021 Mar 17;. doi: 10.1002/ijc.33569. [Epub ahead of print] PubMed PMID: 33729568; PubMed Central PMCID: PMC9211384. Journal cover article.
4. Berglund A, Amankwah EK, Kim YC, Spiess PE, Sexton WJ, Manley B, Park HY, Wang L, Chahoud J, Chakrabarti R, Yeo CD, Luu HN, Pietro GD, Parker A, Park JY. Influence of gene expression on survival of clear cell renal cell carcinoma. Cancer Med. 2020 Nov; 9(22):8662-8675. doi: 10.1002/cam4.3475. Epub 2020 Sep 28. PubMed PMID: 32986937; PubMed Central PMCID: PMC7666730
5. Xu K, Wang Z, Copland JA, Chakrabarti R, Florczyk SJ. 3D porous chitosan-chondroitin sulfate scaffolds promote epithelial to mesenchymal transition in prostate cancer cells. Biomaterials. 2020 Sep; 254:120126. doi: 10.1016/j.biomaterials.2020.120126. Epub 2020 May 22. PubMed PMID: 32480094.
6. Andl T, Ganapathy K, Bossan A, Chakrabarti R. MicroRNAs as Guardians of the Prostate: Those Who Stand before Cancer. What Do We Really Know about the Role of microRNAs in Prostate Biology?. Int J Mol Sci. 2020 Jul 7;21(13). doi: 10.3390/ijms21134796. Review. PubMed PMID: 32645914; PubMed Central PMCID: PMC7370012.
7. Ganapathy K, Staklinski S, Hasan MF, Ottman R, Andl T, Berglund AE, Park JY, Chakrabarti R. Multifaceted Function of MicroRNA-299-3p Fosters an Antitumor Environment Through Modulation of Androgen Receptor and VEGFA Signaling Pathways in Prostate Cancer. Sci Rep. 2020 Mar 20;10(1):5167. doi: 10.1038/s41598-020-62038-3. PubMed PMID: 32198489; PubMed Central PMCID: PMC7083835.
8. Shahid M, George TB, Saller J, Haija M, Sayegh Z, Boulware D, Strosberg J, Chakrabarti R, Coppola D. FGD4 (Frabin) Overexpression in Pancreatic Neuroendocrine Neoplasms. Pancreas. 2019 Nov/Dec;48(10):1307-1311. doi: 10.1097/MPA.0000000000001422. PubMed PMID: 31688594; PubMed Central PMCID: PMC7771383.
9. Xu K, Ganapathy K, Andl T, Wang Z, Copland JA, Chakrabarti R, Florczyk SJ. 3D porous chitosan-alginate scaffold stiffness promotes differential responses in prostate cancer cell lines. Biomaterials. 2019 Oct;217:119311. doi: 10.1016/j.biomaterials.2019.119311. Epub 2019 Jun 28. PubMed PMID: 31279100.
10. Bossan A, Ottman R, Andl T, Hasan MF, Mahajan N, Coppola D, Chakrabarti R. Expression of FGD4 positively correlates with the aggressive phenotype of prostate cancer. BMC Cancer. 2018 Dec 17;18(1):1257. doi: 10.1186/s12885-018-5096-9. PubMed PMID: 30558664; PubMed Central PMCID: PMC6296060.
11. Pease BN, Huttlin EL, Jedrychowski MP, Dorin-Semblat D, Sebastiani D, Segarra DT, Roberts BF, Chakrabarti R, Doerig C, Gygi SP, Chakrabarti D. Characterization of Plasmodium falciparum Atypical Kinase PfPK7- Dependent Phosphoproteome. J Proteome Res. 2018 Jun 1;17(6):2112-2123. doi: 10.1021/acs.jproteome.8b00062. Epub 2018 Apr 30. PubMed PMID: 29678115; NIHMSID:NIHMS1068513.
12.Ottman R, Levy J, Grizzle WE, Chakrabarti R. The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer. Oncotarget. 2016 Nov 8;7(45):73739-73753. doi: 10.18632/oncotarget.12061. PubMed PMID: 27650539; PubMed Central PMCID: PMC5340125.
13. Ritchey L, Chakrabarti R. Aurora A kinase modulates actin cytoskeleton through phosphorylation of Cofilin: Implication in the mitotic process. Biochim Biophys Acta. 2014 Nov;1843(11):2719-29. doi:10.1016/j.bbamcr.2014.07.014. Epub 2014 Aug 1. PubMed PMID: 25090971; PubMed Central PMCID: PMC4190833.
14. Ottman R, Nguyen C, Lorch R, Chakrabarti R. MicroRNA expressions associated with progression of prostate cancer cells to antiandrogen therapy resistance. Mol Cancer. 2014 Jan 3;13:1. doi: 10.1186/1476-4598-13-1. PubMed PMID: 24387052; PubMed Central PMCID: PMC3896800.
15. Kaufman JJ, Ottman R, Tao G, Shabahang S, Banaei EH, Liang X, Johnson SG, Fink Y, Chakrabarti R, Abouraddy AF. In-fiber production of polymeric particles for biosensing and encapsulation. Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15549-54. doi: 10.1073/pnas.1310214110. Epub 2013 Sep 9. PubMed PMID: 24019468; PubMed Central PMCID: PMC3785740.
1. Chakrabarti D, Chakrabarti R. Administration of aurora kinase inhibitors for antimalarial therapy. US 11,072,587. Issued 07/27/2021
2. Chakrabarti R, Ottman R, Coppola D, Mahajan, N. Methods for diagnosis and prognosis of epithelial tumors. US 10,655,185. Issued 05/19/2020
3. Chakrabarti R. Increased taxane sensitivity in cancer cells. US 9,532,972. Issued 01/03/2017
4. Chakrabarti R. Co-targeting of Aurora A kinase and LIM kinase 1 for cancer therapy. US 8,911,725. Issued 12/16/2014
5. Chakrabarti R. Methods and compositions for inhibiting the proliferation of cancer cells. US 8,802,649. Issued 08/12/2014
6. Chakrabarti R. Methods and compositions for Inhibiting the proliferation of cancer cells. US 8,415,315. Issued 04/09/2013
For complete list of publications in My Bibliography https://www.ncbi.nlm.nih.gov/myncbi/ratna.chakrabarti.1/bibliography/public/
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