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 primarily concerned with understanding the effects of dietary genistein on intestinal 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.  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. Moreover, we have recently shown that increased dietary genistein reduces the dependence of CF mice for laxatives.  Current work is aimed to evaluate how genistein mediates  benficial effect on survival and weight gain in CF mice.   Recently, we have shown that diabetic/obese ob/ob mice have significantly reduced jejunal basal chloride secretion, and furthermore, we demonstrate that consuming genistein-diet will rescue this deficit in basal secretion.  An additional project in my lab is aimed to evaluate the effects of genistein and exercise in mice fed a high-fat/high-sugar diet (a model of diet-induced diabetic obesity, known to lead to Alzheimer's like pathology).

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.

Selected Publications (See PubMed results

underlined= Student co-authors from the Al-Nakkash lab

Buchan, L. St Aubin CR, Fisher AL, Hellings A, Castro M, Al-Nakkash L, Broderick TL, Plochocki JH.  (2018). BMC Res Notes. 2018 Oct 22;11(1):752. doi: 10.1186/s13104-018-3862-z.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198361/

Lord, R.

Fairbourn N, Mylavarapu C, Dbeis A, Bowman T, Chandrashekar A, Banayat T, Hodges CA, Al-Nakkash L. (2018). Consuming Genistein Improves Survival Rates in the Absence of Laxative in ΔF508-CF Female Mice. Nutrients. 2018 Oct 3;10(10). pii: E1418. doi: 10.3390/nu10101418. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213472/

Rockwood, S.,

T.L. Broderick, and L. Al-Nakkash.  (2018). Feeding obese diabetic mice a genistein diet induces thermogenic and metabolic change. J. Medicinal Food. 1-8 https://www.ncbi.nlm.nih.gov/pubmed/29261006

 Kaufman, J.A., M.J. Castro, N. Sandoval-Skeet and L. Al-Nakkash. (2018). Optical clearing of small intestine for three-dimensional visualization of cellular proliferation within crypts.  J Anatomy. Jan; 232(1): 152-157. doi: 10.1111/joa.12711. https://www.ncbi.nlm.nih.gov/pubmed/28967147
Baker, J., L. Al-Nakkash and M.M. Herbst-Kralovetz. (2017). Estrogen-gut microbiome axis; Physiological and clinical implications. Maturitas. 103:45-53. https://www.ncbi.nlm.nih.gov/pubmed/28778332
Al-Nakkash, L., Utilizing a dietary supplement to modify small intestinal secretory function. J. Nutrition and Food Science. (2016). 6(6): 1-2. DOI: 10.4172/2155-9600.1000e134.
Odle, B., N. Dennison, N. L. Al-Nakkash, T.L. Broderick  & J. H. Plochocki. (2017). Genistein treatment improves fracture resistance in obese diabetic mice.  BMC Endocrine Disorders. 17: https://www.ncbi.nlm.nih.gov/pubmed/28183304
Schacht, S.,

F. Masood, S. Catmull, R, Dolan, R. Altabtabaee, W. Grow & L. Al-Nakkash. (2017). Dietary genistein influences numbers of acetylcholine receptors in female diabetic mouse jejunum. Journal Diabetes Research. 1-9. doi:  10.1155/2017/3568146, PMCID: PMC5556993 https://www.ncbi.nlm.nih.gov/pubmed/28835900

Catmull, S.,   

F. Masood, S. Schacht, R. Dolan, D. Stegman, L. Leung and L. Al-Nakkash. (2016). Dietary genistein rescues reduced basal chloride secretion in diabetic jejunum via sex-dependent mechanisms. Cell. Physiol & Biochem. 40: 335-346. PMID: 27866192 https://www.ncbi.nlm.nih.gov/pubmed/27866192

Leung, L., Leung L, Martin JB, Lawmaster T, Arthur K, Broderick TL, Al-Nakkash L. (2016). Sex-Dependent Effects of Dietary Genistein on Echocardiographic Profile and Cardiac GLUT4 Signaling in Mice. Evid Based Complement Alternat Med. 2016;2016:1796357. doi: 10.1155/2016/1796357. Epub 2016 Jul 4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947657/
Simperova A, Al-Nakkash L, Faust JJ, Sweazea KL. (2016). Genistein supplementation prevents weight gain but promotes oxidative stress and inflammation in the vasculature of female obese ob/ob mice. Nutr Res. 2016 Aug;36(8):789-97. doi: 10.1016/j.nutres.2016.03.011. Epub 2016 Apr 1.
Michelin, R.,
 L. Al-Nakkash, T.L. Broderick, & J.H. Plochocki. (2016). Effects of genistein treatment on
tibial histomorphology in ob/ob mice. Diabetes, Metabolic Syndrome and obesity: Targets and Therapy. Journal of Diabetes & Metabolic Disorders. 9: 63-70. https://www.ncbi.nlm.nih.gov/pubmed/27042131
 Leung, L.,  A. Bhakta, K. Cotangco & L. Al-Nakkash.  (2015). Genistein stimulates murine jejunum
chloride secretion via an Akt-mediated pathway in intact female mice. Cellular Physiology & Biochemistry. 35:1317-1325. https://www.ncbi.nlm.nih.gov/pubmed/25721972
 Rayyan, E.,
S. Polito,  L. Leung, A. Bhakta, J. Kang, J. Willey, W. Mansoor, M.L. Drumm  and L.
Al-Nakkash
.  (2015). The effects of genistein on basal jejunum chloride secretion in R117H CF mice is sex- and route-specific. Clinical and Experimental Gastroenterology.8: 77-87.
Leung, L., J. Kang, E. Rayyan, A. Bhakta, B. Barrett, D. Larsen, R. Jelinek, J. Willey, S. Cochran,T.L. Broderick, and L. Al-Nakkash. (2014). Decreased basal chloride secretion and altered CFTR protein, villin, GLUT5 protein expression in jejunum from ob/ob mice. Diabetes, Metabolic Syndrome and obesity: Targets and Therapy.4(7): 312-330.
Ramos, J.E.,   Al-Nakkash, L., Peterson, A., Gump, B.S., Janjulia, T., Moore, M.S., Broderick, T.L. and Carroll C.C. (2012). The soy isoflavone genistein inhibits the reduction in Achilles tendon collagen content induced by ovariectomy in rats. Scand. J. Med. Sports. 22(5): e108-114.
Al-Nakkash, L., (2012). 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., Martin, J.B.,  Petty, D., Lynch, S.M., Hamrick, C., Lucy, D.,  Robinson, J., Peterson, A., Rubin L.J. and Broderick. T.L. (2012). Dietary genistein induces sex-dependent effects on murine body weight, serum profiles, and vascular function of thoracic aortae. Gender Medicine. 9(5): 295-308.

CURRENT TEACHING ACTIVITIES

I am the Medical Physiology Course Director: Winter PHYSG 1521 & 1523 and Spring PHYSG 1532 & 1534

I participate in the following team-taught Physiology courses:

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

BP, EKG, Smooth Muscle, Membrane Channels, 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 and EKG sections

PHYS 1502 Human Physiology 2 3 credits

 

College of Health Sciences: Fall

Respiration section