Resume

• 1977

  Doctor of Philosophy (Ph.D.)

  Cell Biology and Anatomy

  McGill University

• 1974

  Master of Science (M.Sc.)

  Cell Biology and Anatomy

  McGill University

• 1970

  Society for the Study of Reproduction

  Canadian Fertility and Andrology Society

  English

  French

  Chinese (Mandarin)

  Chinese (Cantonese)

  B.A.

  Biology

  Charter member and Treasurer of the Iota Mu Chapter of the National Tri-Beta Biological Honor Society

  Doane College

  U.S.A.

  Vice-President (1972-1973) and President (1973-1974) of the Doane College Foreign Students'​ Society

  \nElected to Who's Who Among Students in American Colleges and Universities (1974)

  Doane College (now Doane University)

  U.S.A.

• 427

  Methods and compositions for enhancing fertility and/or inhibiting pregnancy failure

  restoring glucose tolerance and/or preventing glucose tolerance and/or maintaining glucose homeostasis and/or inducing or enhancing weight loss

  treating dyslipidemia

  treating hypertestosteronism or hyperandrogenism

  and/or treating type 2 diabetes in an individual in need thereof are provided. These involve compositions that inhibit expression of interferon (IFN)-gamma or a downstream IFN-gamma-stimulated gene

  which is preferably a macrolide immunosupressant compound.

  METHODS AND COMPOSITIONS FOR ENHANCING FERTILITY AND/OR INHIBITING PREGNANCY FAILURE AND RESTORING GLUCOSE TOLERANCE

  US 9

  433 B2

  Ahmad J. H. Albaghdadi

• Data Analysis

  Gamete Biology

  Research

  Reproductive Health

  Cell Culture

  Life Sciences

  Leadership

  Teaching

  Cell Biology

  Management

  Reproductive Biology

  Molecular Biology

  Training

  Scientific Writing

  Immunocytochemistry

  Science

  University Teaching

  Glycoproteins and Glycobiology

  Tacrolimus in the Prevention of Adverse Pregnancy Outcomes and Diabetes-Associated Embryopathies in The New-Zealand Obese and Diabetic Mice

  Ahmad Albaghdadi

  Melanie Hewitt

  Samantha Putos

  Michael Wells

  Terence Ozolinš

  Journal of Translational Medicine

  T2DM is a high-risk pregnancy with adverse fetal and maternal outcomes including repeated miscarriages

  pre-eclampsia and fetal malformations. Despite the established association between placental insufficiency and poor maternal Th1-adaptability to the development of pregnancy complications in T2DM

  there have been no established data to assess benefits of pre-pregnancy immunosuppression relative to gestational outcomes in T2DM. We hypothesized that pre-pregnancy macrolide immune suppression can re-establish normal placental development and uterine vascular adaptation in a mouse model of T2DM.\n Our data suggest a casual association between chronic maternal overnutrition and the development of materno-fetal comorbidities manifested in the immune-mediated glucose intolerance

  defective spiral arteriolar modification

  placental insufficiency and adverse fetal outcomes in a mouse model of the human obesity-associated T2DM. We have specifically found that the use of tacrolimus at the dose of 0.1mg/kg q2d is adequate in restoring glucose homeostasis prior to and during gestation in the obese and diabetic subjects. The weight of evidence from pregnancies following solid organ transplant points to the embryo-fetal safety of in utero tacrolimus exposure. Metformin normalized glucose intolerance in HFD-dNONcNZO mice but offered less protection against diabetes-induced embryopathies than tacrolimus. This suggests that the etiology

  incidence and severity of diabetes-induced congenital anomalies may have an immunological component requiring appropriate immuno-therapeutic intervention. \n\n

  Tacrolimus in the Prevention of Adverse Pregnancy Outcomes and Diabetes-Associated Embryopathies in The New-Zealand Obese and Diabetic Mice

  Diabesity is often associated with subfertility and recurrent miscarriages. Evidence links systemic and\nlocal uterine cytotoxicity to the pathogenesis of implantation failure (IF) in diabetes. Immunosuppression\nwith tacrolimus improved pregnancy outcomes in obese and diabetic mice and repeated IF in women\nwith elevated Th1/Th2 blood cell ratios. However the mode of action of tacrolimus in protecting against\nIF and the molecular mechanisms associated with recurrent miscarriages in the obese and diabetic\nsubjects are yet to be elucidated. Here we administered tacrolimus (FK506) (0.1 mg/kg) for four\nconsecutive weeks to the NONcNZO10/LtJ mice

  a model of human PCOS

  chronically fed with 60% kCal\nfat for 16 consecutive weeks to simulate human obesity-associated T2DM. Compared to those immunosuppressed with tacrolimus and their controls

  high-fat fed (HFD) diabetic NONcNZO mice exhibited higher rates of peri- and post-implantation resorption and had aberrant expression of uterine IFNg and progesterone receptor (PGR) and its immunophilin co-chaperone FKBP52 at nidation. Immature uterodomes and lack of activation of uterine STAT3 and NFkB at implantation were characteristics of IF in the HFD-dNONcNZO dams also low in the deciduogenic factors IL11 and GM-CSF. Therapeutic interventions with tacrolimus or metformin normalized the expression of decidual IFNg

  PGR and FKBP52

  increased co-localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted in the upregulation of uterine IL11and LIF. Rescued phosphorylation of STAT3 and NFkBp65 and uterodome maturation at nidation defined implantation success in treated dams. To our knowledge this is the first report to show that the impact of HFD on the hemochorial implantation is at least in part mediated through disruption of PGR signaling at nidation and that immunosuppression with tacrolimus or treatment with metformin restores PGR-mediated influences during implantation in the obese and diabetic subjects.\n

  Immunosuppression with tacrolimus improved implantation and rescued expression of uterine progesterone receptor and its co-regulators FKBP52 and PIASy at nidation in the obese and diabetic mice: Comparative studies with metformin

  Ahmad J H. Abaghdadi

  Stephanie L. Shorter

  Tissue and Cell

  In the present study

  we examined the morphology of cilia and expression of the dynein intermediate chain 2 (DNAI2) in the oviduct of non-obese diabetic (NOD) mice. Results obtained with immunohistochemistry showed that DNAI2 expression was reduced in oviducts of diabetic NOD (dNOD) mice

  as compared to that observed in the normoglycemic NOD (cNOD) group

  especially in the acyclic dNOD mice. Oviductal cilia of dNOD mice appeared to be reduced in number. Results obtained with Western blot analysis revealed that the expression of DNAI2 protein was significantly less in oviducts of dNOD mice as compared to that of cNOD mice corroborating the results obtained with immunohistochemistry. Electron microscopic examination and quantitative imaging of thin sections of Epon-embedded oviducts of both dNOD and cNOD mice confirmed the reduction of the number of cilia in the oviduct of the dNOD group which also displayed aberrant axonemal ultrastructure

  including disorganization of the axoneme and alteration of microtubule doublets into singlets as well as disruption of the plasma membrane in many cilia. Taken together

  the present findings suggest that structural alterations of oviductal cilia in female diabetic mice might be detrimental to the normal function of these particular cell structures in gamete transport.

  Alterations in Oviductal Cilia Morphology and Reduced Expression of Axonemal Dynein in Diabetic NOD Mice

  Recombinant human oviductin regulates protein tyrosine phosphorylation and acrosome reaction

  Robert L. Reid

  Zongchao Jia

  Yuewen Zhao

  The mammalian oviduct synthesizes and secretes a major glycoprotein known as oviductin (OVGP1) which has been shown to interact with gametes and early embryos. We report here the use of recombinant DNA technology to produce

  for the first time

  the secretory form of human OVGP1 in HEK293 cells. HEK293 colonies stably expressing recombinant human OVGP1 (rHuOVGP1) were established by transfecting cells with an expression vector pCMV6-Entry constructed with OVGP1 cDNA. Large quantities of rHuOVGP1 were obtained from the stably transfected cells using the CELLSPIN cell cultivation system. A two-step purification system was carried out to yield rHuOVGP1 with purity of >95%. Upon gel electrophoresis

  purified rHuOVGP1 showed a single band corresponding to the 120-150 kDa size range of human OVGP1. Mass spectrometric analysis of the purified rHuOVG1 revealed its identity as human oviductin. Immunofluorescence showed the binding of rHuOVGP1 to different regions of human sperm cell surfaces in various degrees of intensity. Prior treatment of sperm with 1% Triton X-100 altered the immunostaining pattern of rHuOVGP1 with an intense immunostaining over the equatorial segment and post-acrosomal region as well as along the length of the tail. Addition of rHuOVGP1 in the capacitating medium was found to further enhance tyrosine phosphorylation of sperm proteins in a time-dependent manner. After 4 hours of incubation in the presence of rHuOVGP1

  the number of acrosome-reacted sperm induced by calcium ionophore significantly increased. The successful production of rHuOVGP1 can now facilitate the study of the role of human OVGP1 in fertilization and early embryo development.

  Recombinant human oviductin regulates protein tyrosine phosphorylation and acrosome reaction

  Frederick W. K.

  Kan

  National Institutes of Health

  Université de Montréal

  McGill University

  Queen's University

  Montreal

  Quebec

  Canada

  Postdoctoral Fellow

  Department of Anatomy and Cell Biology

  Faculty of Medicine

  McGill University

  Montreal

  Quebec

  Canada

  Postdoctoral Research Fellow

  McGill University

  Montreal

  Quebec

  Canada

  Associate Professor

  Université de Montréal

  Kingston

  Ontario

  Canada

  Professor of Anatomy and Cell Biology

  Department of Biomedical and Molecular Sciences (Present position)\nActing Head

  Department of Anatomy and Cell Biology

  (07/2001-06-2002)

  \nDesignated Director

  Research Group in Reproduction

  Development and Sexual Function (2002-2004)

  \nRecipient of a Scholarship (MRC Scholar) from the Medical Research Council (MRC) of Canada (1987-1992)\nChercheur-Boursier (Research Scholar) Junior II

  FRSQ

  Quebec

  Canada (07/1990-06/1992)

  \nChercheur-Boursier (Research Scholar) Junior I

  FRSQ

  Quebec

  Canada (07/1987-06/1990)

  \nInvited Visiting Scientist (Host: Laboratory of Cellular and Developmental Biology

  National Institutes of Diabetes and Kidney Diseases

  N.I.H.

  Bethesda

  Maryland

  U.S.A.) sponsored by a MRC Travelling Award (1991)\nRecipient of the \"Murray L. Barr Junior Scientist Award\" from the Canadian Association of Anatomy

  Neuroanatomy and Cell Biology (1990)\n

  Professor

  Dept. of Biomedical & Molecular Sciences

  Faculty of Health Sciences

  Queen's University

  Queen's University

  Montreal

  Quebec

  Canada

  Assistant Professor

  Université de Montréal

  Bethesda

  Maryland

  U.S.A.

  Postdoctoral Research Fellow

  Membrane Biology Section

  Laboratory of Pathophysiology

  NCI-NIH

  Bethesda

  Maryland

  U.S.A. (January 1984 - August 1984)\n\nPostdoctoral Research Fellow

  Membrane Biology Section

  Laboratory of Pathophysiology

  Frederick Cancer Research Facility

  NCI-NIH

  Frederick

  Maryland

  U.S.A. (September 1984 - June 1985)

  Postdoctoral Research Fellow

  National Institutes of Health