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Layla Al-Nakkash, Ph.D.

Professor


 

Arizona College of Osteopathic Medicine
Department of Physiology
Midwestern University
Agave Rm 217J
19555 N 59th Ave.
Glendale, AZ 85308

Office: 623-572-3719
Lab:623-572-3475
Fax: 623-572-3673
e-mail: lalnak@midwestern.edu 

 

 

 

EDUCATION
B.Sc.   Physiology University of Newcastle-Upon Tyne, England, UK
Ph.D.   Physiology UNiversity of Newcastle-Upon Tyne, England, UK

Post-doctoral Fellow at Case Western Reserve University and University of Missouri-Columbia

RESEARCH SUMMARY

The research in my lab is concerned with two major areas: understanding the effects of dietary genistein on intestinal function and on vascular function.

Genistein is an isoflavonic phytoestrogen found naturally in soy, and a known in vitro activator of the CFTR chloride channel, presumably via a direct binding to the channel itself. Cystic fibrosis (CF) is an inherited disease in which epithelia are adversely affected by loss of proper CFTR function (i.e. sweat duct, pancreas, vas deferens, airway and intestine).  We hypothesized that increased dietary genistein intake in mice would have beneficial effects on intestinal epithelial chloride secretion, i.e. elicit increased chloride secretion. We have shown that increased dietary genistein increases basal and cAMP-mediated chloride secretion in female wild-type (Wt) murine jejuna, but interestingly not in males. Moreover, we have shown that increased dietary genistein reduces the dependence of CF mice for laxatives. The well established CF mouse model has an intestinal pathology (intestinal obstruction, seen clinically in some CF patients) and thus requires permanent use of laxatives for survival. Current studies are aimed at determining the mechanism(s) of action of genistein on intestinal function in Wt, CF and ob/ob  mice, and understanding the sex-dependent differences observed.

Epidemiological data suggests that those human populations that consume large quantities of soy products have multiple beneficial health effects including: inhibition of angiogenesis, improved vascular function and decreased cardiovascular disease. Furthermore, due to health concerns regarding hormone replacement therapy, women have turned to phytoestrogens as an alternative treatment. The effects of genistein are likely mediated via multiple pathways including and certainly not limited to; activation of estrogen receptors, inhibition of tyrosine kinase activity, direct effects on channels (chloride, calcium and potassium). We utilize a mouse model to determine the effects of chronic dietary genistein on cardiac and vascular function. We have found increases in tension generated in aortic vascular reactivity experiments in both males and females fed increased dietary genistein compared to a genistein-free diet. Current studies are aimed at determining the mechanism(s) responsible for generating the effects of dietary genistein. Considering recent controversies regarding efficacy of hormone replacement therapy on cardiovascular health and the marketing emphasis on use of natural products, such as soy, our studies are prudent and timely to better understand the physiological effects of unregulated nutritional supplements.


Selected Publications (See PubMed results)

Al-Nakkash,L.,      Martin, J.B.,  Petty, D., Lynch, S.M., Hamrick, C., Lucy, D.,  Robinson, J., Peterson, A., Rubin L.J. and Broderick. T.L. Dietary genistein induces sex-dependent effects on murine body weight, serum profiles, and vascular function of thoracic aortae. (2012). Gender Medicine. 9(5): 295-308.
   
 Ramos, J.E,
Al-Nakkash, L., Peterson, A., Gump, B.S., Janjulia, T., Moore, M.S., Broderick, T.L. and Carroll C.C. The soy isoflavone genistein inhibits the reduction in Achilles tendon collagen content induced by ovariectomy in rats. (2012). Scand. J. Med. Sports. 22(5): e108-114.
 
 Al-Nakkash, L.,
Genistein stimulates jejunal chloride secretion via sex-dependent, estrogen receptor or adenylate cyclase mechanisms. (2012). Cell. Physiol. Biochem. 30(1): 137-150.
   
 Al-Nakkash, L.,
Batia, L., Bhakta, M., Peterson, A., Hale, N., Skinner, R., Sears, S. and Jensen J. Stimulation of murine intestinal secretion by daily genistein injections: gender-dependent differences. (2011). Cell. Physiol. Biochem. 28(2): 239-250.
Al-Nakkash, L., Markus, B., Batia, L., Prozialeck, W.C. and Broderick, T.L. (2010). Genistein induces estrogen-like effects in ovariectomized rats but fails to increase cardiac GLUT4 and oxidative stress. J. Med. Food. 13(6): 1369-75.
Al-Nakkash, L., Markus, B., Bowden, K., Batia, L., Prozialeck, W.C. and Broderick, T.L. (2009). Effects of acute and 2-day genistein on cardiac function and ischemic tolerance in ovariectomized rats. Gender Med. 6(3): 488-97.
Al-Nakkash, L., Springsteel, M.F., Kurth, M.J., and Nantz, M.H. (2008). Activation of CFTR by UCCF-029 and genistein. Bioorg. Med. Chem. Lett. 18(14): 3874-7.
Al-Nakkash, L., Clarke, L.L., Rottinghaus, G.E., Chen, Y.J., Cooper, K. and Rubin, L.J. (2006). Dietary genistein stimulates anion secretion across female murine intestine. J. Nutr. 136(11): 2785-90.

 

CURRENT TEACHING ACTIVITIES

This year I am participating in the following team-taught Physiology courses:

 

Arizona College of Osteopathic Medicine (AZCOM):  Winter and Spring

GI and Respiratory sections

PHYS 1521 Physiology I  5.5 credits
PHYS 1532 Physiology II 5.5 credits

Arizona College of Pharmacy (CP-Glendale): Fall

GI section

PHYS 1502 Human Physiology 2 3 credits

 

College of Dental Medicine & College of Optometry Arizona: Winter and Spring

GI and Respiration sections

BASI 1506 Basic Science Integrated Sequence VI 5  credits
BASI 1509 Basic Science Integrated Systems IX 4.7 credits

 


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