Project Service

Ilham El Khattabi, Ph.D

**************@*****.***

** ******** ****, ***. *, Boston, MA 02135. 617-***-****

SUMMARY

Experienced Scientist with extensive and excellent expertise in Cellular and Molecular Biology

within Diabetes and Metabolism diseases area.

RESEARCH EXPERIENCE and ACCOMPLISHEMENTS

Joslin Diabetes Center, Harvard University Medical School, Boston MA

Research Fellow in Medicine. Section of Islet Cell Biology and Regenerative Medicine. 2005 -

2014.

Independently led and managed project exploring the role of a protein called MafA as a

potential novel target for diabetes therapy in the pancreatic beta cell function and proliferation

in normal and oxidative stress conditions:

• Discovered that p38 MAPK is the major signaling pathway that mediates MafA degradation

under oxidative stress and that preventing this degradation can overcome β-cell dysfunction.

• Demonstrated that under oxidative and non-oxidative conditions p38 MAPK directly binds

to MafA and triggers MafA degradation via the ubiquitin proteasomal pathway.

• Demonstrated that enhancing MafA protein expression by targeting one threonine amino

acid only at the N-terminal domain is sufficient to enhance glucose stimulated insulin

secretion in pancreatic beta cell lines and in an in vitro model system of immature neonatal

islets using luminescent and fluorescent gene reporter systems.

• Established and validated new cell-based assays as a powerful tool for MafA targets

identification, gene expression and for studying the role of this protein in the regulation of

pancreatic beta cell function.

• Developed a mouse model to specifically overexpress the protein MafA in pancreatic beta

cells and to study its role in beta cell function and proliferation after birth.

Université Catholique de Louvain, Louvain-la-Neuve, Belgium. Cellular and Molecular

Biology Department.

Doctoral Research Fellow: Thesis title ‘Consequences of dietary protein deficiency on Insulin

like growth factors and Insulin like growth factors binding proteins in fetal rat liver’.

• Established an experimental model of “highly purified” primary cell culture of isolated rat

hepatocytes from fetal rat liver as a powerful technique to verify the in vivo findings and to

study the regulation of IGF/BP system ex vivo.

• Examined the signaling pathways of endocrine hormones (Prolactin and Glucocorticoids)

and nutrients (branched amino acids) on IGFs and IGFBPs using primary culture of

hepatocytes from fetal liver.

Master Research Fellow: Project Title ‘Effect of maternal low protein diet during pregnancy

and lactation on development of endocrine pancreas’

1

Determined the consequences of low protein diet on pancretic beta cell mass, proliferation

•

and apoptosis using immunohistochemistry and morphometric analysis.

EDUCATION

Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

• Ph.D. in Science, Cellular and Molecular Biology, Summa Cum laude, September 2004.

• M.S. in Cellular Biology, Cum Laude, July 1998.

SKILLS and TECHNIQUES

Highly skilled in Cellular, Molecular and Biochemical assays including:

• Extensive expertise in mammalian cell culture including primary (Rodent & human islets,

hepatocytes), cell lines (MIN6, INS-1, αTC, NIH 3T3, HEK-293, HeLa, HepG2….) as well as

mouse embryonic stem cells.

• Protein quantitative analysis (ELISA, RIA using I125, SDS-PAGE, Western Immunoblotting),

protein–protein interaction (Immunoprecipitation).

• Cellular transfection using Gene reporter cell-based assays and generation of stable cell lines.

• qPCR, RT-PCR (Taqman and SybrGreen 96 & 384 wells using 7900HT), Si/ShRNA based

knockdown.

• Virologic methods including production, titration and transduction of adeno and

lentiviruses.

• Gene cloning, DNA sequencing, site-directed mutagenesis, DNA and RNA extraction.

• Proliferation assays using flow cytometry analysis (BrdU, phospho-Histone H3, Propidium

Iodide), cell sorting, DNA content, cell cycle analysis…using FlowJo software.

• Immunofluorescence, Immunohistochemistry, Fluorescent microscopy and Confocal

imaging.

• Animal handling and physiological studies with different in vivo models.

INVITED TALKS

Joslin Tuesday’s Internal Seminar Series: “Role of protein kinases in regulating stability of

•

insulin gene transcription factor MafA”. Joslin Diabetes Center, December 2008.

University of Cambridge, Department of Clinical Biochemistry, Cambridge, UK 2003.

•

Presentations related to Ph.D thesis work

7th International meeting on Fœtal Origin of Adult Diseases (FOAD), Islet of Wight, UK,

•

September 2000, Presentations related to Ph.D thesis work.

GRANTS AWARDS & HONORS

Post-doctoral Fellowship, Ruth L. Kirschstein National Research Service Award, Boston,

•

MA, 2005-2007

Ph.D Fellowship, Université Catholique de Louvain, from Parthenon Trust, London, UK

•

and ‘Fond National de Recherche Scientifique’, Louvain-la-Neuve, Belgium, 1999-2004

2

Travel award for best poster, Second International ‘Growth Hormone & Insulin-like Growth

•

Factor Symposium’, Cairns, Australia, 2004

Best Poster ‘Ph.D. student day’, Louvain-la-Neuve, Belgium 2003

•

PUBLICATIONS

El Khattabi I and Sharma A. Preventing p38 MAPK-mediated MafA degradation ameliorates

Beta-cell function. Molecular Endocrinology 2013; 27 (7), 1078-1090.

Kondo T*, El Khattabi I*, Nishimura W, Laybutt DR, Geraldes P, Shah S, King G, Bonner-Weir

S, Weir G and Sharma A. p38 MAPK is a major regulator of MafA protein stability under

oxidative stress. Molecular Endocrinology 2009; 23 (8): 1281-1290.*Co-First Author.

El Khattabi I, Reusens B, Remacle C. The regulation of IGFs and IGFBPs by prolactin in primary

culture of foetal rat hepatocytes is influenced by maternal malnutrition. The American Journal

of Physiology-Endocrinology and Metabolism 2006; 291(4): E835-E842.

El Khattabi I, Grégoire F, Remacle C, Reusens B. Isocaloric maternal low protein diet alters IGF-

I, IGFBPs and hepatocytes proliferation in fœtal rat. The American Journal of Physiology-

Endocrinology and Metabolism 2003; 285(5): E991-E1000.

Jermendy A, El Khattabi I, Vetere A, Lock J, Bee YM, Mazzucato CA, Bonner-Weir S Sharma A.

Glucose-responsiveness of mature beta cells is dependent on MafA function. 2014 (Under

Revision).

Hu He K*, Juhl K*, Karadimos M, El Khattabi I, Fitzpatrick C, Bonner-Weir S, Sharma A.

Misexpression of MafA in endocrine progenitors blocks their differentiation following

commitment to specific endocrine cell fate. Developmental Biology 2014; 385 (1), 2-12.

Mazzucato CA, Zavacki AM, Marinelarena A, Hollister-Lock J, El Khattabi I, Marsili A, Weir

GC, Sharma A, Larsen PR, Bonner-Weir S. Thyroid hormone promotes postnatal rat pancreatic

beta cell development and glucose-responsive insulin secretion through MAFA. Diabetes 2013;

62 (5), 1569-1580.

Karadimos MJ, Kapoor A, El Khattabi I, and Sharma A. Beta cell preservation and regeneration

for diabetes treatment: Where are we now? Diabetes Management 2012; 2 (3), 213-222.

Mazzucato CA, Koh A, El Khattabi I, Li WC, Toschi E, Jermendy A, Juhl K, Mao K, Weir GC,

Sharma A, Bonner-Weir S. MafA expression enhances functional maturity of neonatal beta-cells.

Diabetologia 2011; 54; 583-593.

Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, Mlynarski WM, El Khattabi I,

Kim SH, Marselli L, Rich SS, Krolewski AS, Bonner-Weir S, Sharma A, Sale M, Mychaleckyi JC,

Kulkarni RN, Doria A. Mutations at the BLK locus linked to maturity onset diabetes of the

young and beta-cell dysfunction. Proceedings of the National Academy of Sciences (USA) 2009;

106(34): 144**-*****.

3

Nishimura W, Kondo T, Salameh T, El Khattabi I, Dodge R, Bonner-Weir S, Sharma A. A switch

from MafA expression accompanies differentiation to pancreatic beta cells. Developmental

Biology, 2006 293 (2): 526-539.

SELECTED ABSTRACTS

El Khattabi I and Sharma A. MafA stability and beta cell function under oxidative stress are

enhanced by preventing p38 MAPK phosphorylation. 72ndADA annual meeting Philadelphia

2012.

El Khattabi I, Sharma A. Under Oxidative stress p38 MAPK regulates MafA protein stability

through Threonine 134 and not Threonine 57. 71st ADA Annual meeting, San Diego 2011.

Jermendy A, El Khattabi I, Vetere A, Lock Jennifer, Bee YM, Mazzucato CA, Sharma A, Bonner-

Weir S. Glucose responsiveness of mature beta cells is dependent of MafA function. 71st ADA

annual meeting, San Diego 2011.

Jermendy A, Vetere A, El Khattabi I, Bee YM, Mazzucato CA, Sharma A, Bonner-Weir S. MafA

knock-down leads to immature phenotype in mature beta-cells of primary adult rat islets. 70th

ADA annual meeting, Orlando 2010.

El Khattabi I, Kondo T, Nishimura W, Bonner-Weir S, Weir G and Sharma A. p38 MAPK and

GSK3 differentially regulate MafA protein stability. 69th ADA annual meeting, New Orleans

2009.

Mazzucato CA, Koh A, El Khattabi I, Toschi E, Mao K, Sharma A, Bonner-Weir S. Reduced

MafA expression may contribute to the immaturity of neonatal beta cells. 68th ADA Annual

meeting, San Fransisco 2008.

Kondo T*, El Khattabi I*, Nishimura W, Bonner-Weir S, Weir G and Sharma A. p38 MAPK

signaling pathway regulates MafA protein stability. 67th ADA annual meeting, Chicago

2007.*Co-First Author.

Nishimura W, Kondo T, El Khattabi I, Dodge R, Cheng Ho I, Bonner Weir S and Sharma A. Maf

factors are important for the differentiation of pancreatic endocrine cells. 66th ADA annual

meeting, Washington DC 2006.

El Khattabi I, Hinck L, Reusens B, Remacle C. Effect of an isocaloric maternal low protein diet

on the regulation of IGFs and IGFBPs by prolactin in primary culture of foetal rat hepatocytes.

GH & IGF Research 2004, Cairns, Australia.

El Khattabi I, Grégoire F, Remacle C, Reusens B. Proliferation and IGF-Binding Proteins

production by fetal hepatocyte is controlled by the diet of the dam: An in vitro study.

Diabetologia 2001, 44 suppl 1, 37th Annual of the European Association Study for the study of

Diabetes (EASD) meeting, Glaskow, UK.

4

Contact this candidate