Interdisciplinary Life Science - PULSe Great research is a matter of choice

Arpita Pal

Arpita Pal Profile Picture

MSc in Molecular Medicine, University of Sheffield, Sheffield, UK


Contact Info:

pal2@purdue.edu
7654099505


Training Group(s):
Molecular Signaling and Cancer Biology


Current Research Interests:

 Lipocalin2 (LCN2) is a 24 kDa protein, secreted by several normal and malignant tissues in various pathologic states. Its role as an iron transporter is well established. However, it is now becoming apparent that LCN2 has roles in inflammation and cancers. LCN2 modulates the immune system by functioning as a chemoattractant for neutrophils. In cancers, several mechanisms have been implicated. In breast cancer, LCN2 in the microenvironment interacts with Matrix Metalloproteinase-9 (MMP-9) inducing invasiveness. Whereas in leukemia, LCN2 exerts its tumorigenic effects on normal cells via the microenvironment through paracrine signaling. LCN2 has multi-faceted roles and multiple mechanisms, producing very contradictory roles in different malignancies. For example, in thyroid, breast, lung and pancreatic cancers LCN2 can be either pro- or anti- tumorigenic. Our preliminary evidence in a mouse model of pre-B-cell lymphoma indicates a positive correlation of LCN2 in the serum of diseased mice. Lymphoma in these mice was induced through overexpression of a single microRNA (miRNA), miR-21 suggesting that miR-21 may be involved in LNC2 upregualtion1,2. An additional lymphoma model that develops disease through overexpression of miR-155 was not evaluated for LCN2; however, we hypothesized a similar effect on LCN2. Since miR-21 and miR-155 are two commonly upregulated miRNAs in Non Small Cell Lung Cancer (NSCLC), which continues to be devastating despite advancements in therapeutics, we are applying our data from the lymphoma models to study LCN2 in NSCLC. We also sought to identify additional miRNAs that regulate LCN2, since thus far only miR-138 is reported to downregulate LCN2. This led us to hypothesize that the NSCLC tumorigenesis and chemoresistance mediated by LCN2 is in part through miRNA-mediated regulation. To this end, we first identified LCN2 protein expression and secretion in a panel of NSCLC cell lines. High LCN2 producing and secreting NCI-H441 cells expressed high levels of miR-21 but low levels of miR-155. Conversely, low miR-21 and high miR-155 were identified in low LCN2 producing and secreting immortalized, normal Human Bronchial Epithelial Cells (HBEC). Overexpression of miR-21 and miR-155 in the panel demonstrated up- and downregulated LCN2 respectively; and opposing effects upon antagonizing miR-21 and miR-155. These results depict a regulatory mechanism exerted by miR-21 and miR-155 on LCN2 , but whether it is through the 3'- or 5'- untranslated regions or the promoter of LCN2, will be further evaluated through delineating the interaction using luciferase reporter constructs. Additionally, bioinformatically predicted miRNAs will be evaluated to define their involvement in LCN2 regulation.



Selected Publications:

 Pal A, Melling G, Hinsley EE, Kabir TD, Colley HE, Murdoch C, Lambert DW (2012). Cigarette smoke condensate promotes pro-tumourigenic stromal-epithelial interactions by suppressing miR-145. J Oral Pathol Med. 2013 Apr; 42(4):309-14.

  • Student Profile

Ernest C. Young Hall, Room 170 | 155  S. Grant Street, West Lafayette, IN 47907-2114 | 765-494-2600

© 2017 Purdue University | An equal access/equal opportunity university | Copyright Complaints | Maintained by The Purdue University Graduate School

If you have trouble accessing this page because of a disability, please contact The Purdue University Graduate School.