Description of Research:
We investigate the unexplored features of molecules, mechanisms and pathways involved in the cancer development. The overarching aim is to get deeper insights into etiology and the processes of carcinogenesis, which may help, in its prevention, identification of new drug targets or in the improvement in the prognosis. Currently, my laboratory focus on the following projects:
Unveiling new drug targets: We have evidence of a possible role of proteins like ‘Rho A’ in cancer cell proliferation and metastasis through contact with novel interacting partners. Currently, we are exploring the impact of disrupting such interactions on hallmark features of cancer including proliferation and metastasis with aim of assessing the potential of such interaction for therapeutic intervention.
Regulation of Glucose metabolism by TP53: Although the antitumor role of TP53 is well understood, the impact of its antagonistic or assisting proteins on its regulation of glucose metabolism is not well studied. We focus on the regulation of G6PD that catalyzes the key step in pentose phosphate pathway.
Epigenetics of esophageal squamous cell carcinoma (ESCC): Epigenetic modifications alter the expression of genes and contribute in the process of disease development like cancers. More insights are needed, to know how the epigenetic modifications cause cancers including ESCC. From whole transcriptome analysis of ESCC tissues, we have identified some novel epigenetic markers whose expression was substantially elevated as compared to their expression in normal esophageal tissues. We are assessing the effects of such high expression of epigenetic proteins on certain unexplored genes involved in neovascularization and apoptosis
Prognostic model and Etiology of esophageal squamous cell carcinoma: Kashmir valley, the extreme north of India has high incidence of esophageal squamous cell carcinoma (ESCC). Due to its peculiar socio-cultural, geographical and climatic features, it offers a suitable setting to carry out epidemiological studies for understanding the etiology of ESCC. We have been able to pin point certain epidemiological and genetic risk factors of this cancer (Ref. Publications) and the findings can be of tremendous importance in prevention of the cancer in Kashmir. However, for better understanding of the environmental, dietary and hereditary causes of esophageal cancer, we have taken up some more studies.
We have shortlisted 1000 genetic markers to develop to study their influence in determining the treatment response. The association with treatment outcomes of ESCC patients with genetic markers along with tumor patient and epidemiological features will be assimilated into a prognostic model for ESCC to foretell the response of a patient to a particular treatment.
Peer Reviewed Publications:
1 Shah IA, Mehta P, Lone MM, Rasool MT, Lone GN, Gulzar GM, Ganie FA, Bhat MA, Dar NA. CYP1A2*1F Gene Variant, Alkaline Salt Tea Intake and Risk of Esophageal Squamous Cell Carcinoma. Nutr Cancer. 2018 Jan;70(1):146-152. doi: 10.1080/01635581.2018.1412482. Epub 2017 Dec 26.
2 Murphy G, McCormack V, Abedi-Ardekani B, Arnold M, Camargo MC, Dar NA,. et al. International cancer seminars: a focus on esophageal squamous cell carcinoma. Ann Oncol. 2017 Sep 1;28(9):2086-2093.
3 Bhat GA, Bhat AB, Lone MM, Dar NA. Association of Genetic Variants of CYP2C19 and CYP2D6 with Esophageal Squamous Cell Carcinoma Risk in Northern India, Kashmir. Nutr Cancer. 2017 May-Jun;69(4):585-592.
4 Iqbal B, Masood A, Lone MM, Lone AR, Dar NA. Polymorphism of Metastasis Suppressor Genes MKK4 and NME1 in Kashmiri Patients with Breast Cancer. Breast J. 2016 Nov;22(6):673-677.
5 Shah IA, Bhat GA, Mehta P, Lone MM, Dar NA. Genotypes of CYP1A1, SULT1A1 and SULT1A2 and risk of squamous cell carcinoma of esophagus: outcome of a case-control study from Kashmir, India. Dis Esophagus. 2016 Nov;29(8):937-943.
6 Dar NA. Narghile Smoking is Associated With the Development of Oral Cancer at Early Age. J Evid Based Dent Pract. 2015 Sep;15(3):126-7.
7 Shah IA, Mehta P, Lone MM, Dar NA. Leu432Val Polymorphism of CYP1B1 is Not Associated with Squamous Cell Carcinoma of Esophagus--a Case-Control Study from Kashmir, India.Asian Pac J Cancer Prev. 2015;16(13):5337-41.
8 Bhat GA, Shah IA, Rafiq R, Nabi S, Iqbal B, Lone MM, Islami F, Boffetta P, Dar NA. Family history of cancer and the risk of squamous cell carcinoma of oesophagus: a case-control study in Kashmir, India. Br J Cancer. 2015 Jun 30. doi: 10.1038/bjc.2015.218. [Epub ahead of print] PubMed PMID: 26125444.
9 Iqbal B, Shah IA, Bhat GA, Bhat AB, Rafiq R, Nabi S, Malekhzadeh R, Abnet CC, Boffetta P, Jenab M, Dar NA. Impediments in foreign collaboration and onducting a high throughput molecular epidemiology research in India, an assessment from a feasibility study. Springerplus. 2015 Jun 23;4:287. doi: 10.1186/s40064-015-1046-z. eCollection 2015. PubMed PMID: 26120504;
10 Makhdoomi MA, Shah IA, Bhat GA, Amin S, Lone MM, Islami F, Dar NA. Association between GSTM1 and GSTT1 polymorphisms and esophageal squamous cell carcinoma: results from a case-control study in Kashmir, India. Tumour Biol. 2015Apr;36(4):2613-9. doi: 10.1007/s13277-014-2882-0. Epub 2014 Nov 29. PubMed PMID: 25432134.
11 Dar NA, Bhat GA, Shah IA, Iqbal B, Rafiq R, Nabi S, Lone MM, Islami F, Boffetta P. Salt tea consumption and esophageal cancer: a possible role of alkaline everages in esophageal carcinogenesis. Int J Cancer. 2015 Mar 15;136(6):E704-10. doi: 10.1002/ijc.29204. Epub 2014 Oct 6. PubMed PMID: 25209106.
12 Bhat GA, Shah IA, Makhdoomi MA, Iqbal B, Rafiq R, Nabi S, Masood A, Lone MM, Dar NA. CYP1A1 and CYP2E1 genotypes and risk of esophageal squamous cell carcinoma in a high-incidence region, Kashmir. Tumour Biol. 2014 Jun;35(6):5323-30. doi: 10.1007/s13277-014-1694-6. Epub 2014 Feb 8. PubMed PMID:24504680.
13 Andrabi M, Hussain A, Rashid F, Nissar SO, Shah IA, Rather YH, Ahangar WH, Dar NA. Chromosome 18p11.2 harbors susceptibility marker: D18S452, for bipolar affective disorder. Indian J Psychiatry. 2013 Oct;55(4):371-5. doi:10.4103/0019-5545.120567. PubMed PMID: 24459309; PubMed Central PMCID: PMC3890926.
14 Dar NA, Islami F, Bhat GA, Shah IA, Makhdoomi MA, Iqbal B, Rafiq R, Lone MM,
Boffetta P. Contact with animals and risk of oesophageal squamous cell arcinoma: outcome of a case-control study from Kashmir, a high-risk region. Occup Environ Med. 2014 Mar;71(3):208-14. doi: 10.1136/oemed-2013-101802. Epub 2014 Jan 9. PubMed PMID: 24406322.
15 Dar NA, Islami F, Bhat GA, Shah IA, Makhdoomi MA, Iqbal B, Rafiq R, Lone MM,
Abnet CC, Boffetta P. Poor oral hygiene and risk of esophageal squamous cell
carcinoma in Kashmir. Br J Cancer. 2013 Sep 3;109(5):1367-72. doi: 10.1038/bjc.2013.437. Epub 2013 Jul 30. PubMed PMID: 23900216; PubMed Central PMCID: PMC3778293.
16 Dar NA, Shah IA, Bhat GA, Makhdoomi MA, Iqbal B, Rafiq R, Nisar I, Bhat AB,
Nabi S, Masood A, Shah SA, Lone MM, Zargar SA, Islami F, Boffetta P. Socioeconomic status and esophageal squamous cell carcinoma risk in Kashmir,
India. Cancer Sci. 2013 Sep;104(9):1231-6. doi: 10.1111/cas.12210. Epub 2013 Jul PubMed PMID: 23721087.
17 Dar NA, Islami F, Boffetta P. Reply: false positive result in study on hookah smoking and cancer in Kashmir: measuring risk of poor hygiene is not the same as measuring risk of inhaling water-filtered tobacco smoke all over the world. Br J Cancer. 2013 Apr 2;108(6):1391-2. doi: 10.1038/bjc.2013.99. Epub 2013 Mar 7. PubMed PMID: 23470467; PubMed Central PMCID: PMC3619268.
18 Abedi-Ardekani B, Dar NA, Mir MM, Zargar SA, Lone MM, Martel-Planche G, Villar S, Mounawar M, Saidi F, Malekzadeh R, Hainaut P. Epidermal growth factor receptor (EGFR) mutations and expression in squamous cell carcinoma of the esophagus in central Asia. BMC Cancer. 2012 Dec 17;12:602. doi: 10.1186/1471-2407-12-602. PubMed PMID: 23244191;
19 Dar NA, Bhat GA, Shah IA, Iqbal B, Makhdoomi MA, Nisar I, Rafiq R, Iqbal ST, Bhat AB, Nabi S, Shah SA, Shafi R, Masood A, Lone MM, Zargar SA, Najar MS, Islami F, Boffetta P. Hookah smoking, nass chewing, and oesophageal squamous cell carcinoma in Kashmir, India. Br J Cancer. 2012 Oct 23;107(9):1618-23. doi: 10.1038/bjc.2012.449. Epub 2012 Oct 2. Erratum in: Br J Cancer. 2013 Apr 16;108(7):1552. Kakhdoomi, M A [corrected to Makhdoomi, M A]. PubMed PMID: 23033008; PubMed Central PMCID: PMC3493783.
20 Qureshi MA, Jan N, Dar NA, Hussain M, Andrabi KI. A novel p16(INK4A) mutationassociated with esophageal squamous cell carcinoma in a high risk population. Biomarkers. 2012 Sep;17(6):552-6. doi: 10.3109/1354750X.2012.699556. Epub 2012 Jun 22. PubMed PMID: 22724384.
21 Salam I, Hussain S, Mir MM, Dar NA, Abdullah S, Siddiqi MA, Lone RA, Zargar SA, Sharma S, Hedau S, Basir SF, Bharti AC, Das BC. Aberrant promoter methylation and reduced expression of p16 gene in esophageal squamous cell carcinoma from Kashmir valley: a high-risk area. Mol Cell Biochem. 2009 Dec;332(1-2):51-8. doi: 10.1007/s11010-009-0173-7. Epub 2009 Jun 10. PubMed PMID: 19513816.
22 Mir MM, Dar NA. Esophageajl cancer in kashmir (India): an enigma for researchers. Int J Health Sci (Qassim). 2009 Jan;3(1):71-85. PubMed PMID: 21475514; PubMed Central PMCID: PMC3068781.
23 Dar NA, Mir MM, Salam I, Malik MA, Gulzar GM, Yatoo GN, Ahmad A, Shah A Association between cojpper excess, zinc deficiency, and TP53 mutations in esophageal squamous cell carcinoma from Kashmir Valley, India--a high risk area. Nutr Cancer. 2008;60(5):585-91. doi: 10.1080/01635580802290231. PubMed PMID:18791921.
24 Mir MM, Dar JA, Dar NA, Dar MS, Salam I, Lone MM, Chowdary NA. Combined
impact of polymorphism of folate metabolism genes; glutamate arboxypeptidase, methylene tetrahydrofolate reductase and methionine synthase reductase on breast cancer susceptibility in kashmiri women. Int J Health Sci (Qassim). 2008 Jan;2(1):3-14. PubMed PMID: 21475466; PubMed Central PMCID: PMC3068715.
25 Mir MM, Dar JA, Dar NA, Syed AT, Salam I, Lone GN. The Association of Beta-catenin Gene Mutations and Human Papillomavirus in Carcinoma of Esophagus in a High-Risk Population of India. Int J Health Sci (Qassim). 2007 Jul;1(2):177-83. PubMed PMID: 21475426; PubMed Central PMCID: MC3068640.
26 de Moraes E, Dar NA, de Moura Gallo CV, Hainaut P. Cross-talks between cyclooxygenase-2 and tumor suppressor protein p53: Balancing life and death during inflammatory stress and carcinogenesis. Int J Cancer. 2007 Sep 1;121(5):929-37. Review. PubMed PMID: 17582597.
27 Benoit V, de Moraes E, Dar NA, Taranchon E, Bours V, Hautefeuille A, Tanière P, Chariot A, Scoazec JY, de Moura Gallo CV, Merville MP, Hainaut P. Transcriptional activation of cyclooxygenase-2 by tumor suppressor p53 requires nuclear factor-kappaB. Oncogene. 2006 Sep 21;25(42):5708-18. Epub 2006 May 8. PubMed PMID: 16682957.
28 Mir MM, Dar NA, Gochhait S, Zargar SA, Ahangar AG, Bamezai RN. p53 mutation profile of squamous cell carcinomas of the esophagus in Kashmir (India): a high-incidence area. Int J Cancer. 2005 Aug 10;116(1):62-8. PubMed PMID: 15761872.
29 Mir MM, Khan AR, Dar NA, Salahuddin M. Polymorphonuclear leukocyte mediated oxidative inactivation of alpha-1-proteinase inhibitor: Modulation by nitric oxide. Indian J Clin Biochem. 2005 Jan;20(1):184-92. doi: 10.1007/BF02893068. PubMed PMID: 23105520; PubMed Central PMCID: PMC3454178.