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.

Afaq F, Adhami VM and Ahmad N. Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice. Toxicology and Applied Pharmacology, 186:28-37, 2003.

Afaq F, Adhami VM, Ahmad N and Mukhtar H. Inhibition of ultraviolet B-mediated activation of nuclear factor kappa B in normal human epidermal keratinocytes by green tea constituent (-)-epigallocatechin-3-gallate. Oncogene, 22:1035-1044, 2003.

Afaq F, Saleem M, Aziz MH and Hasan Mukhtar. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion markers in CD-1 mouse skin by oleandrin. Toxicology and Applied Pharmacology, 195:361-369, 2004.

Afaq F, Saleem M, Krueger CG, Reed JD, Mukhtar H. Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in CD-1 mice. International Journal of Cancer, 113: 423-433, 2005.

Afaq F, Malik A, Syed D, Maes D, Matsui M, Mukhtar H. Pomegranate fruit extract modulates UVB-mediated phosphorylation of mitogen activated protein kinases and activation of nuclear factor Kappa B in normal human epidermal keratinocytes. Photochemistry and Photobiology,81: 38-45, 2005.

Afaq F, Adhami VM, Mukhtar H. Photochemoprevention of ultraviolet B signaling and photocarcinogenesis.  Mutation Research, 571: 153-173, 2005.

Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proceeding of National Academy of Science, USA, 102: 14813-14818, 2005.

Sarfaraz S, Afaq F, Adhami VM, Malik A, Mukhtar H. Cannabinoid receptor agonist-induced apoptosis of human prostate cancer cells LNCaP proceeds through sustained activation of ERK1/2 leading to G1 cell cycle arrest. Journal of Biological Chemistry, 281:39480-39491, 2006.

Syed DN,  Afaq F, Kweon M-H, Hadi N, Bhatia N, Spiegelman VS, Mukhtar H. Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-kB activation in normal human bronchial epithelial cells. Oncogene, 26: 673-682, 2007.

Afaq F, Syed DN, Malik A, Hadi N, Sarfaraz S, Kweon M-H, Khan N, Zaid M, Mukhtar H. Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis. Journal of Investigative Dermatology, 127: 222-232, 2007.

Afaq F, Zaman N, Khan N, Syed DN, Sarfaraz S, Zaid MA, Mukhtar H. Inhibition of epidermal growth factor receptor signaling pathway by delphinidin, an anthocyanidin in pigmented fruits and vegetables. International Journal of Cancer, 123:1508-1515, 2008.

Afaq F, Zaid MA, Khan N, Dreher M, Mukhtar H. Protective effect of pomegranate-derived products on UVB-mediated damage in human reconstituted skin. Experimental Dermatology, 18:553-561, 2009.

Afaq F, Zaid MA, Pelle E, Khan N, Syed DN, Matsui MS, Maes D, Mukhtar H. Aryl hydrocarbon receptor is an ozone sensor in human skin. Journal of Investigative Dermatology, 129:2396-2403, 2009.

Syed DN, Afaq F, Maddodi N, Johnson JJ, Sarfaraz S, Ahmad A, Setaluri V, Mukhtar H. Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels. Journal of Investigative Dermatology, 131:1291-1299, 2011.

Afaq F. Natural agents: cellular and molecular mechanisms of photoprotection.  Archives of Biochemistry and Biophysics, 508:144-151, 2011.

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. Photochemistry and Photobiology, 2012 [Epub ahead of print].

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.

UAB SDRC Pilot and Feasibility Grant Program               Afaq F (PI)           07/01/11-06/30/12
Combinatorial Approach for Prevention of Melanoma
The major goal of this project is to identify the effect of fisetin alone and in combination with sorafenib for prevention of melanoma.

CA13148-39 UAB CCC JFDG Program                            Afaq F (PI)           07/01/11-06/30/12
Targeting EGFR and VEGFR-2 by Dietary Anthocyanidin Delphinidin     
The major goal of this project is to identify non-toxic, inexpensive dietary agent for the prevention and treatment of lung cancers.