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Area of Research:
Stem
Cells, microRNA and Gene Expression, Microarray, ESCs, iPSCs
and Regenerative medicine, Cancer Stem cells, Computational
Genomics, Epigenetics and reprogramming of induced pluripotent
stem cells, microRNAs in disease networks & systems biology
A fundamental
question in stem cell biology is what determines the
self-renewal and pluripotency of stem cells? Recent data
indicate that RNAi may play an important role in these
processes. We aim to understand the role of small regulatory
RNAs specially microRNA in the self-renewal and pluripotency
of embryonic stem cells(ES cells) and induced pluripotent stem
cells (iPS cells). We plan to analyze the miRNA and mRNA
microarray data of both ES and iPS cells systematically and
investigate the function of individual miRNAs in these and
identify their target genes. Moreover, we have identified
particular miRNAs that are likely candidate genes for several
human diseases like SARS, ischemic heart disease.
Apart from ES and
iPS cells, recently we are interested to gear our research
towards a small subpopulation of cells identified in cancers
that have stem cell properties. These cells hopefully will
come up with appropriate answers to the following questions:
Why are most cancers difficult to eradicate and easy to recur
and metastasize? Why are some tumors resistant to therapy? Why
are some tumors highly aggressive? Are we targeting the right
cells? Cancer stem cells (CSCs) are thus the cells within a
tumor that possess the capacity to self-renew and produce
heterogeneous lineages of cancer cells that comprise the tumor.
The self-renewing CSC is characterized by continuous expansion
of cells in cancer resulting in the development of a tumor,
unlike normal stem cells in which the total number of stem
cells in a tissue is highly regulated and expansion beyond the
normal level is restricted by genetic programs. MicroRNAs have
recently been shown to be acting as micro-switches that reveal
certain hidden dimensions of CSC cycle control. We aim towards
elucidating miRNA-mediated regulatory networks in CSCs.
Key
Publications:
Hu S, Wilson KD,
Ghosh Z, Han L, Wang Y, Lan F, Ransohoff KJ, Wu JC (2012)
MicroRNA-302 increases reprogramming efficiency via repression
of NR2F2. Stem Cells. 2012. Pubmed ID:
23136034.
Kumar R, Halder P, Sahu SK, Kumar M, Kumari M, Jana K, Ghosh
Z, Sharma P, Kundu M, Basu J (2012) Identification of a novel
role of ESAT-6-dependent miR-155 induction during infection of
macrophages with Mycobacterium tuberculosis. Cell
Microbiol. 2012 14(10):1620-1631. PubMed ID:
22712528.
Reddy S, Zhao M, Hu DQ, Fajardo G, Hu S, Ghosh Z, Rajagopalan
V, Wu JC, Bernstein D (2012) Dynamic microRNA expression
during the transition from right ventricular hypertrophy to
failure. Physiol Genomics. 44(10):562-575. PubMed ID:
22454450.
Ghosh Z,
Huang M, Hu S,
Wilson KD, Dey D, Wu JC
(2011) Dissecting the oncogenic and tumorigenic potential of differentiated Human induced pluripotent stem cells and human embryonic stem cells. Cancer
Research, 71(14): 5030–5039.
PubMed ID: 21646469.
Pearl JI, Leveson-Gower
DB, Lee A, Sun N, Ghosh Z, Negrin RS, Davis MM, Wu JC (2011)
Inducing immunotolerance to pluripotent stem cells for
long-term engraftment. Cell Stem Cell, 8(3):309-317. PubMed ID:
21362570. [Highlighted in
ScienceDaily]
Hu S, Huang M, Li
Z, Jia F, Ghosh Z, Lijkwan MA, Fasanaro P, Sun N, Wang X,
Martelli F, Robbins RC, Wu JC (2010) MicroRNA-210 as a novel
therapy for treatment of ischemic heart disease.
Circulation, 122 (11 Suppl):S124-31. PubMed ID:
20837903.
Ghosh Z, Wilson KD,
Wu Y, Hu S, Quertermous T, Wu JC (2010) Persistent donor cell
gene expression among human induced pluripotent stem cells
contributes to differences with human embryonic stem cells.
PLoS One, 5(2):e8975. PubMed ID:
20126639.
Wilson KD, Hu S,
Venkatasubrahmanyam S, Fu JD, Sun N, Abilez OJ, Baugh JJ, Jia
F, Ghosh Z, Li RA, Butte AJ, Wu JC (2010) Dynamic microRNA
expression programs during cardiac differentiation of human
embryonic stem cells: role for miR-499. Circ Cardiovasc
Genet., 3(5):426-35. PubMed ID:
20733065.
Ghosh Z, Mallick
B, Chakrabarti J (2009) MicroRNome analysis unravels the
molecular basis of SARS infection in bronchoalveolar stem
cells. PLoS One, 4(11):e7837. PubMed ID:
19915717.
Ghosh Z, Mallick
B, Chakrabarti J. Cellular versus viral microRNAs in
host-virus interaction (2010) Nucleic Acids Res.,
37(4):1035-48. PubMed ID:
19095692.
Köhrer C,
Srinivasan G, Mandal D, Mallick B, Ghosh Z, Chakrabarti J,
Rajbhandary UL (2008) Identification and characterization of a
tRNA decoding the rare AUA codon in Haloarcula marismortui.
RNA, 14(1):117-26. PubMed ID:
17998287. (featured on journal cover)
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