Farrukh Afaq, Ph.D.


afaq

  

University of Alabama at Birmingham
VH 509
1720 2ND AVE S
BIRMINGHAM AL 35294-0009

Office: (205) 934-5190
fafaq@uab.edu  



Faculty Appointment:   Assistant Professor of Dermatology
Associate Scientist, Cancer Chemoprevention Program, CCC
B.S.   Aligarh Muslim University, Aligarh, India,
Chemistry, 1989
M.S.   Aligarh Muslim University, Aligarh, India,
Biochemistry, 1991
M.Phil.   Aligarh Muslim University, Aligarh, India,
Biochemistry, 1995
PhD.   Aligarh Muslim University, Aligarh, India,
Biochemistry, 1998
 

Research Interests

 

Dr. Afaq’s research interests are to identify critical cellular and molecular targets in skin photocarcinogenesis, photoaging and other hyperproliferative and inflammatory skin diseases. He has devoted a greater part of his efforts in understanding how commonly consumed dietary ingredients can be exploited for the prevention and treatment of skin cancers (i.e. non-melanoma and melanoma). His studies have shown that anthocyanidins- and hydrolyzable tannins-rich pomegranate fruit extract possess strong anti-inflammatory and anti-tumor promoting properties in mouse models of photocarcinogenesis, and he is currently studying the molecular mechanism(s) of these inhibitory effects. Recently, he has found that fisetin (3,7,3′,4′-tetrahydroxyflavone), a naturally occurring flavonoid, has anti-proliferative, pro-apoptotic and anti-invasive effects on melanoma cells by targeting PI3K/AKT/mTOR and BRAF-MEK-ERK signaling pathways, which are activated in melanoma and are associated with poor prognosis. His research also focuses on the combinatorial approach for the prevention/treatment of melanoma. He is investigating the effects of fisetin in combination with sorafenib on cell proliferation, invasion and epithelial-to-mesenchymal transitions in melanoma cell lines with different genetic backgrounds, tissue-engineered three dimensional skin equivalents and mouse models. In addition, he is investigating the effect of delphinidin and abundant fruits and vegetables based anthocyanidin on markers of epidermal differentiation, proliferation and inflammation by employing in vitro three dimensional models of reconstituted normal and psoriatic human skin, and an in vivo mouse model of psoriasis.

Another area of his research interest is the prevention/treatment of lung cancer. He has found that delphinidin is an effective inhibitor of EGFR and VEGFR-2 in non-small-cell lung cancer cells. He is now investigating the effect of delphinidin on cell proliferation, invasion and apoptosis by the simultaneous blockage of EGFR and VEGFR-2 and their downstream signaling pathways by using cell cultures and a mouse model of lung cancer. These studies will help ascertain that EGFR and VEGFR-2 positive lung cancers may be amendable to therapeutic intervention by delphinidin.

 

Selected Publications

Arumugam A, Weng Z, Talwelkar SS, Chaudhary SC, Kopelovich L, Elmets CA, Afaq F, Athar M. Inhibiting Cycloxygenase and Ornithine Decarboxylase by Diclofenac and Alpha-Difluoromethylornithine Blocks Cutaneous SCCs by Targeting Akt-ERK Axis. PLoS One. 2013 Nov 8;8(11):e80076.


Chaudhary SC, Singh T, Talwelkar SS, Srivastava RK, Arumugam A, Weng Z, Elmets CA, Afaq F, Kopelovich L, Athar M. Erb-041, an estrogen receptor beta agonist inhibits skin photocarcinogenesis in SKH-1 hairless mice by down-regulating WNT signaling pathway. Cancer Prev Res (Phila). 2013 Dec 19.


Pal HC, Sharma S, Strickland LR, Agarwal J, Athar M, Elmets CA, Afaq F. Delphinidin reduces cell proliferation and induces apoptosis of non-small-cell lung cancer cells by targeting EGFR/VEGFR2 signaling pathways. PLoS One. 2013 Oct 4;8(10):e77270.


Srivastava RK, Li C, Chaudhary SC, Ballestas ME, Elmets CA, Robbins DJ, Matalon S, Deshane JS, Afaq F, Bickers DR, Athar M. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption. Toxicol Appl Pharmacol. 2013 Nov 1;272(3):879-87.


Li C, Srivastava RK, Elmets CA, Afaq F, Athar M. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein. Biochem Biophys Res Commun. 2013 Sep 6;438(4):607-12.


Pal HC, Sharma S, Elmets CA, Athar M, Afaq F. Fisetin inhibits growth, induces G₂ /M arrest and apoptosis of human epidermoid carcinoma A431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation. Exp Dermatol. 2013 Jul;22(7):470-5.


Li C, Weng Z, Doran SF, Srivastava RK, Afaq F, Matalon S, Athar M. Chlorine induces the unfolded protein response in murine lungs and skin. Am J Respir Cell Mol Biol. 2013 Aug;49(2):197-203.


Chamcheu JC, Afaq F, Syed DN, Siddiqui IA, Adhami VM, Khan N, Singh S, Boylan BT, Wood GS, Mukhtar H. Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models. Exp Dermatol. 2013 May;22(5):342-8.


Arumugam A, Walsh SB, Xu J, Afaq F, Elmets CA, Athar M. Combined inhibition of p38 and Akt signaling pathways abrogates cyclosporine A-mediated pathogenesis of aggressive skin SCCs. Biochem Biophys Res Commun. 2012 Aug 24;425(2):177-81.


Syed DN, Afaq F, Mukhtar H. Differential activation of signaling pathways by UVA and UVB radiation in normal human epidermal keratinocytes. Photochem Photobiol. 2012 Sep-Oct;88(5):1184-90.


Khan N, Syed DN, Pal HC, Mukhtar H, Afaq F. Pomegranate fruit extract inhibits UVB-induced inflammation and proliferation by modulating NF-κB and MAPK signaling pathways in mouse skin. Photochem Photobiol. 2012 Sep-Oct;88(5):1126-34.


Afaq F, Katiyar SK. Polyphenols: skin photoprotection and inhibition of photocarcinogenesis. Mini Rev Med Chem. 2011 Dec;11(14):1200-15. Review.


Khan N, Adhami VM, Afaq F, Mukhtar H. Butein induces apoptosis and inhibits prostate tumor growth in vitro and in vivo. Antioxid Redox Signal. 2012 Jun 1;16(11):1195-204.


Afaq F. Natural agents: cellular and molecular mechanisms of photoprotection. Arch Biochem Biophys. 2011 Apr 15;508(2):144-51.

 
Grant Support

 5R21AT004966-03                                                            Afaq F (PI)           04/01/10-03/31/13
NIH/NCCAM                                        
Delphinidin: A Novel Agent for Treatment of Psoriasis
The major goal of this project is to identify the usefulness of delphinidin for treatment of psoriatic lesions.


1R21CA173043-01A1                                                        Afaq F (PI)             04/01/14-04/31/14
NIH/NCI
Combinatorial Approach for Reducing Invasive Potential of Melanoma Cells
The major goal of this project is to establish the importance of fisetin in combination with sorafenib or other drugs for the management of melanoma cell invasion or metastasis.