Sk. Kayum Alam

Postdoctoral Research Associate , Ph.D.

20162017
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Personal profile

Research interests

Lung cancer is the most common cause of cancer-related death in men and second most common in women. Non-small cell lung cancer (NSCLC) represents 85% of all lung cancer and carries a very poor survival rate: less than 15% of patients survive more than 5 years. For many years, systematic chemotherapy has been the most effective treatment for NSCLC, despite its many pitfalls. Recently, molecular targeted therapies have emerged that are substantially changing the management of lung cancer. These treatments include drugs that precisely inhibit the driver mutation. Despite an expanding panel of chemotherapy agents and molecular targeted therapies, drug resistance has continued to pose a significant challenge in the management of NSCLC. Previously, our group demonstrated that dopamine and D2 receptor agonists inhibit vascular endothelial growth factor (VEGF)-mediated angiogenesis and lung tumor growth in mice. Dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32) is a downstream signaling molecule of dopamine D2 receptor. Recent studies have shown DARPP-32 and its truncated splice-variant, t-DARPP, are overexpressed and mediate drug resistance in breast and gastric cancer cells. In light of these findings, we speculate that overexpression of DARPP-32 and t-DARPP in NSCLC may activate oncogenic signaling and their cumulative effects promote tumor growth and drug resistance. We overexpressed DARPP-32 and t-DARPP in human A549 NSCLC cells and assessed whether their overexpression regulated genes implicated in promotion of drug resistance and tumor growth. Following quantitative PCR-based super array studies, we plotted z-transformed expression values and generated a heat map of differentially expressed genes. We identified a variety of oncogenes, tumor suppressors, and drug resistance genes regulated by DARPP-32 and t-DARPP compared to controls. Correspondingly, we demonstrated that A549 cells overexpressing DARPP-32 or t-DARPP exhibit increased tumor growth in an orthotopic mouse model. Next, we sought to understand how expression of DARPP-32 and t-DARPP in lung cancer contributes to drug resistance. To that end, we overexpressed or silenced DARPP-32 and t-DARPP in a variety of NSCLC cell lines and determined whether DARPP-32 isoform expression levels altered the proliferation of lung cancer cells in the presence of molecular targeted drugs widely used for treatment of NSCLC. Currently, we are focusing on understanding the mechanism through which DARPP-32 and t-DARPP regulate the expression of specific genes to promote drug resistance in lung cancer. The elucidation of new mechanisms of drug resistance and development of novel precision therapies will help make significant strides in improving lung cancer patient treatments.

Education/Academic qualification

PhD, IICB

Jul 28 2009Feb 10 2016

Keywords

  • drug resistance
  • cancer cell biology

Fingerprint The Fingerprint is created by mining the titles and abstracts of the person's research outputs and projects/funding awards to create an index of weighted terms from discipline-specific thesauri.

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Research Output 2016 2017

5 Citations (Scopus)

p53 gain-of-function mutations increase Cdc7-dependent replication initiation

Datta, A., Ghatak, D., Das, S., Banerjee, T., Paul, A., Butti, R., Gorain, M., Ghuwalewala, S., Roychowdhury, A., Alam, S. K., Das, P., Chatterjee, R., Dasgupta, M., Panda, C. K., Kundu, G. C. & Roychoudhury, S., Nov 1 2017, In : EMBO Reports. 18, 11, p. 2030-2050 21 p.

Research output: Contribution to journalArticle

Open Access
Mutation
Cells
Neoplasms
Peptide Initiation Factors
DNA Replication
32 Citations (Scopus)

DNA damage-induced ephrin-B2 reverse signaling promotes chemoresistance and drives EMT in colorectal carcinoma harboring mutant p53

Alam, S. K., Yadav, V. K., Bajaj, S., Datta, A., Dutta, S. K., Bhattacharyya, M., Bhattacharya, S., Debnath, S., Roy, S., Boardman, L. A., Smyrk, T. C., Molina, J. R., Chakrabarti, S., Chowdhury, S., Mukhopadhyay, D. & Roychoudhury, S., Apr 1 2016, In : Cell Death and Differentiation. 23, 4, p. 707-722 16 p.

Research output: Contribution to journalArticle

Open Access
Ephrin-B2
Epithelial-Mesenchymal Transition
DNA Damage
Colorectal Neoplasms
p53 Genes
8 Citations (Scopus)

E2 ubiquitin-conjugating enzyme, UBE2C gene, is reciprocally regulated by wild-type and gain-of-function mutant p53

Bajaj, S., Alam, S. K., Roy, K. S., Datta, A., Nath, S. & Roychoudhury, S., Jul 1 2016, In : Journal of Biological Chemistry. 291, 27, p. 14231-14247 17 p.

Research output: Contribution to journalArticle

Open Access
Ubiquitin-Conjugating Enzymes
M Phase Cell Cycle Checkpoints
Anaphase
Genes
Ubiquitin
16 Citations (Scopus)

MicroRNA profiling of cisplatin-resistant oral squamous cell carcinoma cell lines enriched with cancer-stem-cell-like and epithelial-mesenchymal transition-type features

Ghosh, R. D., Ghuwalewala, S., Das, P., Mandloi, S., Alam, S. K., Chakraborty, J., Sarkar, S., Chakrabarti, S., Panda, C. K. & Roychoudhury, S., Apr 5 2016, In : Scientific reports. 6, 23932.

Research output: Contribution to journalArticle

Open Access
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
MicroRNAs
Cisplatin
Squamous Cell Carcinoma
6 Citations (Scopus)

Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53

Datta, A., Dey, S., Das, P., Alam, S. K. & Roychoudhury, S., Jun 1 2016, In : Genomics Data. 8, p. 47-51 5 p.

Research output: Contribution to journalArticle

Open Access
Floxuridine
Gene Expression Profiling
Colorectal Neoplasms
Genes
Cells