Prof. Sherif Karam       
       
Professor
Department of Anatomy
Phone: 971 3 7137 493
Fax: 971 3 7672033
Email: skaram@uaeu.ac.ae


College of Medicine and Health Sciences

United Arab Emirates University
P.O.Box 17666, Al-Ain
United Arab Emirates
Education:
Ph.D. (McGill University)
Research Interests:
Gastric epithelial cell biology

Our interests focus on the general phenomena of renewing epithelia: cell proliferation, differentiation, migration and death (apoptosis). In these epithelia, over 90% of human cancers occur via a multi-step process which starts by alteration in the proliferation/differentiation program of the stem cells.

In the stomach, the glandular epithelium represents an attractive model to study all these phenomena. It has numerous short pits continuous with long tubular glands made of isthmus, neck and base regions (Fig. 1). The pluripotential stem cells are anchored in the isthmus region and give rise to several committed precursors which undergo migration-associated differentiation to replace the degenerating mucous, parietal, zymogenic, enteroendocrine and caveolated cells. All these cells can be identified by untrastructural features, or by multilabel immunocytochemistry using cell-specific biomarkers (Fig. 2), or by some functional assays. We are trying to understand cell lineage interrelationships and the key factors that control the dynamism of the gastric epithelial stem cells and the allocation/commitment of their hierarchies along the pit-gland units in both normal and altered conditions. In addition, the structure-function relationship of the parietal cells is of particular interest because of the tremendous morphological and biochemical changes that occur in these cells during and after acid secretion.

Figure 1: Diagram of the gastric unit.

Figure 2: Multilabel immuno- and lectin-histochemically stained section of the gastric mucosa of 3-week-old mouse showing the compartmentalization of gastric units. The pit cells labeled with the green FITC-CTB lectin are seen at the top; neck cells labeled with the red TRITC-GSII lectin are seen in the middle; and parietal cells labeled with the blue AMCA-Lewisx mABs are scattered throughout. (from Karam et al, 1997).

Publications:
  1. Karam SM and CP Leblond: Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell. Anatomical Record 236(2):259-279 (1993)
  2. Karam SM and JG Forte:Inhibiting gastric H+-K+-ATPase activity by omeprazole promotes degeneration and production of parietal cells. American Journal of Physiology, 266 (Gastrointest. Liver Physiol. 29): G745-G758 (1994).
  3. Li Q, SM Karam and JI Gordon: Simian Virus 40 T antigen amplification of pre- parietal cells in transgenic mice: Effects on other gastric epithelial cell lineages and evidence for a p53-independent apoptotic mechanism that operates in a committed progenitor. Journal of Biological Chemistry,270(26):15777-15788 (1995).
  4. Karam SM: New insights into the stem cells and the precursors of the gastric epithelium. Nutrition, 11(5):607-613 (1995).
  5. Li Q, SM Karam and JI Gordon: Diphtheria toxin-mediated ablation of parietal cells in the stomach of transgenic mice. Journal of Biological Chemistry, 271(7):3671-3676 (1996).
  6. Yao X, SM Karam, M. Ramilo, Q. Rong, A Thibodeau and J. G. Forte: Stimulation of gastric acid secretion by cAMP in a novel a-toxin-permeabilized gland model. American Journal of Physiology 271(Cell Physiology 40):C61-C73 (1996).
  7. Karam SM, X Yao and JG Forte: Functional heterogeneity of parietal cells along the pit-gland axis. American Journal of Physiology, 272 (Gastrointest. Liver Physiol. 35): G161-G171 (1997).
  8. Karam SM, Q Li, and JI Gordon: Gastric epithelial morphogenesis in normal and transgenic mice. American Journal of Physiology 272 (Gastrointest. Liver Physiol. 35):G1209-G1220 (1997). 
  9. Li Q, SM Karam, KA Coever, MM Matzuk, and JI Gordon: Stimulation of activin receptor II signaling pathways inhibits differentiation of multiple gastric epithelial lineages. Molecular Endocrinology; 12(2):181-192 (1998).
  10. Karam SM: Cell lineage relationship in the stomach of normal and genetically manipulated mice. Brazilian Journal of Medical and Biological Research., 31:271-279 (1998).
  11. Okamoto CT, SM Karam, YY Jeng, JG Forte and JR Goldenring: Identification of clathrin and clathrin adaptors on tubulovesicles of gastric acid secretory (oxyntic) cells. American Journal of Physiology 274 (Cell Physiology 43) :C1017-C1029 (1998).
  12. Karam SM: Lineage commitment and maturation of epithelial cells in the gut. Frontiers in Bioscinces; 4:D286-298 (1999).
  13. Syder AJ, JL Guruge, Q Li, Y Hu, CM Oleksiewicz, RG Lorenz, SM Karam, PG Falk and JI Gordon: Helicobacter pylori attaches to NeuAc a-2,3Gal betaglycoconjugates produced in the stomach of transgenic mice lacking parietal cells. Molecular Cell; 3(3):263-74 (1999).
  14. Tomasetto C, SM Karam, S Ribieras, R Masson, O Lefebvre, A Staub, Alexander G, Chenard M, Rio MC. Identification and characterization of a novel gastric peptide hormone: the motilin-related peptide. Gastroenterology 119:395-405 (2000).
  15. Karam SM, G Alexander: Blocking of histamine H2 receptors enhances parietal cell degeneration in the mouse stomach. Histology & Histopathology 16(2):469-80 (2001).
  16. Karam SM, G Alexander, V Farook, A Wagdi: Characterization of the rabbit gastric epithelial lineage progenitors in short-term culture. Cell & Tissue Research 306(1):65-74 (2001).
  17. Karam SM, G Alexander, V Farook, and A Wagdi: Characterization of the rabbit gastric epithelial lineage progenitors in short-term culture.  Cell & Tissue Research, 306:65-74 (2001) .
  18. Torres L, SM Karam, C Wendling, M Chenard, D Kershenobich, C Tomasetto, and MC Rio: Trefoil factor 1 (TFF1/pS2) deficiency activates the unfolded protein response.  Molecular Medicine, 8:273-282 (2002).
  19. Alkhalaf M, A El-Mowafy, S Karam:  Growth inhibition of MCF-7 human breast cancer cells by progesterone is associated with cell differentiation and phosphorylation of Akt protein.  European Journal Cancer Preven
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