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Research Interest:
My broad
research interests are to understand the molecular, cellular, and
epigenetic features of esophageal and gastric adenocarcinomas. The
projects I am currently focusing are:
1. Epitomics of Barrett's-Associated esophageal neoplastic
progression
2. Epigenetics in the Pathogenesis of Gastric Cancer
Genetic and epigenetic factors are implicated in the initiation,
development and progression of GC. Epigenetics is a term used to
describe heritable alterations in gene expression that are not due
to changes in DNA sequence, but due to abnormal DNA methylation
patterns. Epigenetic has a key role in carcinogenesis and tumor
progression. In particular, downregulation of tumor suppressor genes
by promoter hypermethylation is an important epigenetic modification
implicated in many cancers. Unlike genetic alterations, which are
almost impossible to reverse, epigenetic aberrations are potentially
reversible, allowing the malignant cell population to revert to a
more normal state. The utilization of epigenetic targets is emerging
as an effective and valuable approach to chemotherapy as well as
chemoprevention of cancer. Identifying the key epigenetic changes
associated with carcinogenesis will help identify targets of
diagnostic and prognostic value.
Selected
Publication:
1.
Rangel1 LBA, Agarwal1 R, D’Souza T,
Pizer ES, Alò PL, Lancaster WD, Gregoire L, Schwartz DR,
Cho KR, Morin PJ (1these authors
contributed equally to the work). Tight Junction Proteins
Claudin-3 and Claudin-4 are Frequently Overexpressed in Ovarian
Cancer but not in Ovarian Cystadenoma. Clinical Cancer Research;
2003; 9: 2567-2575.
2.
Rangel1 LBA, Agarwal1 R,
Sherman-Baust CA,
Mello-Coelho V,
Pizer ES,
Ji H,
Taub DD,
Morin PJ. (1these authors contributed
equally to the work). Anomalous expression of the HLA-DR
alpha and beta chains in ovarian and other cancers. Cancer Biol Ther
2004;3:1021-1027.
3.
D'Souza T,
Agarwal R,
Morin PJ.
Phosphorylation of
claudin-3 at threonine 192 by cAMP-dependent
protein kinase regulates tight junction barrier
function in ovarian cancer cells. J Biol Chem. 2005 Jul; 280(28):
26233-40.
4.
Agarwal R,
D'Souza T, Morin PJ.
Claudin-3 and
claudin-4
expression in ovarian epithelial cells enhances invasion and is
associated with increased matrix metalloproteinase-2 activity.
Cancer Research; 2005; 65:7378-7385.
5.
Hewitt KJ,
Agarwal R,
Morin PJ.
The claudin gene family: expression in normal and neoplastic
tissues.
BMC Cancer. 2006;
12:186.
6.
Zhu TN,
He HJ,
Kole S, D'Souza T,
Agarwal R,
Morin PJ,
Bernier M.
Filamin A-mediated down-regulation of the exchange factor Ras-GRF1
correlates with decreased matrix metalloproteinase-9 expression in
human melanoma cells.
J Biol Chem. 2007; 282:14816-14826.
7.
Jin Z, Mori Y, Yang J, Sato F, Ito T, Cheng Y, Paun B, Hamilton JP,
Kan T, Olaru A, David S, Agarwal R, Abraham JM, Beer D,
Montgomery E, Meltzer SJ. Hypermethylation of the nel-like 1 gene is
a common and early event and is associated with a poor prognosis in
early-stage esophageal adenocarcinoma. Oncogene 2007 Sep
20;26(43):6332-40.
8. Kan T, Paun B, Mori Y, Sato F,
Jin Z, Hamilton JP, Ito T, Cheng Y, David S, Olaru A, Yang J,
Agarwal R, Abraham JM, Meltzer SJ. Rarity of somatic mutation
and frequency of normal sequence variation detected in sporadic
colon adenocarcinoma using high-throughput cDNA sequencing.
Bioinformatics & Biology Insights 2007; 1:1-16.
9. Abraham JM, Sato F, Cheng Y, Paun
B, Ito T, Kan T, Olaru A, Jin Z, Yang J, Agarwal R, David S,
Hamilton JP, Mori Y, Meltzer SJ. A Novel Decapeptide that Binds
Avidly and Delivers Radioisotope to Colon Cancer Cells. PLoS ONE
2007 Oct 3;2(10):e964.
10. Jin Z, Olaru A, Yang J, Sato F, Cheng
Y, Mori Y, Mantzur C, Paun B, Hamilton JP, Ito T, Kan T, Wang S,
David S, Agarwal R, Beer DG,
Abraham JM, Meltzer SJ. Hypermethylation of Tachykinin-1 is
Associated with a Poor Prognosis in Human Esophageal Squamous Cell
Carcinoma. Clin. Cancer Res. 2007 Nov 1;13(21):6293-6300.
11. Jin Z, Mori Y, Hamilton JP, Olaru A,
Sato F, Yang J, Ito T, Paun B, Kan T, Agarwal R, Meltzer SJ.
Hypermethylation of the somatostatin promoter is a common, early
event in human esophageal carcinogenesis. Cancer 2008 Jan
1;112(1):43-49.
12.
Jin Z,
Hamilton JP, Yang J, Mori Y, Olaru A, Sato F, Ito T, Kan T, Cheng Y,
Paun B, David S, Agarwal R, Abraham JM, Meltzer SJ.
Hypermethylation of the AKAP12 Promoter is a Potential Biomarker of
Barrett's-Associated Esophageal Neoplastic Progression. Cancer
Epidemiology, Biomarkers & Prevention 2008 Jan; 17(1):1-16.
13.
Ito T,
Shimada Y, Kan T, David S, Abraham JM, Mori Y, Agarwal R,
Cheng Y, Paun B, Jin Z, Olaru A, Hamilton JP, Yang J, Meltzer SJ,
Sato F. PTTG1 promotes lymph node metastasis in esophageal squamous
cell carcinoma by increasing cell motility. Cancer Research 2008 May
1;68(9):3214-3224.
14. Abraham JM, Cheng Y, Hamilton JP, Paun
B, Jin Z, Agarwal R, Kan T, David S, Olaru A, Yang J, Ito T,
Selaru FM, Mori Y, Meltzer SJ. Generation of small 32P-labeled
peptides as a potential approach to colorectal cancer therapy. PLoS
ONE 2008 Jun 25; 3(6):e2508.
15.
Jin Z,
Hamilton JP, Yang J, Mori Y, Olaru A, Sato F, Ito T, Kan T, Cheng Y,
Paun B, David S, Agarwal R Abraham JM, Meltzer SJ. Promoter
hypermethylation of CDH13 is a common, early event in human
esophageal adenocarcinogenesis and correlates with clinical risk
factors. Int. J. Cancer 2008 Nov 15;123(10):2331-2336.
16. Selaru FM, Olaru AV, Kan T, David S,
Cheng Y, Mori Y, Yang J, Paun B, Jin Z, Agarwal R, Hamilton
JP, Abraham JM, Georgiades C, Alvarez H, Vivekanandan P, Maitra A,
Torbenson M, Thuluvath PJ, Gores GJ, LaRusso NF, Hruban R, Meltzer
SJ. MicroRNA-21 is overexpressed in human cholangiocarcinoma and
regulates programmed cell death 4 and tissue inhibitor of
metalloproteinase 3. Hepatology 2009 Feb 4;49(5):1595-1601.
17. Kan T, Sato F, Ito T, Matsumura N,
David S, Cheng Y, Agarwal R, Paun BC, Jin Z, Olaru AV, Selaru
FM, Hamilton JP, Yang J, Abraham JM, Mori Y, Meltzer SJ. The
miR-25-93-106b polycistron, activated by de novo genomic
amplification, functions as an oncogene by suppressing p21 and Bim.
Gastroenterol. 2009 May;136(5):1689-700.
18. Jin Z, Cheng Y, Zheng Y, Gu J, Sato F,
Olaru AV, Paun B, Yang J, Kan T, Ito T, Hamilton JP, Selaru FM, Mori
Y, Agarwal R, David S, Abraham JM, Wolfsen H, Shaheen NJ,
Wang J, Canto M, Washington K, Romero Y, Wang KK, Feng Z, Sampliner
RD, Meltzer SJ. A multi-center, double-blinded validation study of
methylation biomarkers for progression prediction in Barrett’s
esophagus. Cancer Res. 2009, in press.
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