CDG & Allies - Professionals and Patient Associations International Network (CDG & Allies- PPAIN)
Where families’ own needs and ideas are transformed into research projects.

Work Package 4 
Biology to guide CDG therapies

This Work Package (WP) is formed by several Working Groups (WGs)

Working Group (WG) CDG & Cardioendocrine Heart

Working Group Leader (WGL): Pf Thomas Pulinilkunnil
(Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Nova Scotia, Canada).

This working group is applying Dr Pulinilkunnil´s know-how in the field of adaptive or causative changes in cardiac metabolism causing heart disease to better understand heart and endocrine aspects of CDG and related pathologies.
This research work is being coordinated by Pr Thomas Pulinilkunnil, Dr Duncan Webster (FoG) and Dr Vanessa Ferreira (APCDG).
In addition, his team developed animal models to identify and characterize novel pathways and proteins mediating pathological effects of defective glycosylation. At short-term plan, these models can be used to explore existing therapies and to test new therapeutic approaches. 

Results obtained so far from this research project:
Any student, research groups, researchers, clinicians, patient organisations or other stakeholders who would like to become more involved within this project, are most welcome to get in touch to discuss possible future opportunities and collaborations. Fulfill the contact form available at the end of the page.

Pf Thomas Pulinilkunnil

Biography:
Email: tpulinil@dal.ca
Dr. Pulinilkunnil received his Ph.D. in Cardiovascular Physiology and Pharmacology at the University of British Columbia in Canada. After completion of his doctorate, Dr. Pulinilkunnil joined the Dalhousie Medicine New Brunswick team and has been working as an assistant professor in the Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University since 2012. Dr. Pulinilkunnil built is own Research group and since 2013 he has been training and mentoring undergraduate, Masters and PhD students. Dr Pulinilkunnil´s research group has several interests, even though the adaptive or causative changes in cardiac metabolism cause heart disease were the first and main focus of Dr. Pulinilkunnil’s team. However, using models already established in his laboratory, such as yeast and zebrafish, Pulinilkunnil and his co-workers aim to examine molecular pathways by which impaired glycosylation promotes intracellular distress specifically in organelles like mitochondria, endoplasmic reticulum and lysosomes that are mainly responsible for generating energy, performing quality check on proteins and degrading cellular waste. This research will identify and characterize novel pathways and proteins mediating pathological effects of defective glycosylation, which he and his team hope will have a great positive impact in the lives of people living with CDG.

List of 6 publications in the field of CDG:
  1. O'Neill HM, Lally JS, Galic S, Pulinilkunnil T, Ford RJ, Dyck JR, van Denderen BJ, Kemp BE, Steinberg GR., (2015) Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise. Physiol Rep. 3:e12444 
  2. Schoiswohl G, Stefanovic-Racic M, Menke MN, Wills RC, Surlow BA, Basantani MK, Sitnick MT, Cai L, Yazbeck CF, Stolz DB, Pulinilkunnil T, O'Doherty RM, Kershaw EE., (2015) Impact of Reduced ATGL-Mediated Adipocyte Lipolysis on Obesity-Associated Insulin Resistance and Inflammation in Male Mice. Endocrinology. 156:3610-3624 
  3. Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB., (2014) Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity Nature 00:00 
  4. Zordoky BN, Nagendran J, Pulinilkunnil T, Kienesberger PC, Masson G, Waller TJ, Kemp BE, Steinberg GR, Dyck JR., (2014) AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation. Circ Res. 115:518-524 
  5. O'Neill HM, Lally JS, Galic S, Thomas M, Azizi PD, Fullerton MD, Smith BK, Pulinilkunnil T, Chen Z, Samaan MC, Jorgensen SB, Dyck JR, Holloway GP, Hawke TJ, van Denderen BJ, Kemp BE, Steinberg GR., (2014) AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice. Diabetologia :1693-702 
  6. Kienesberger PC, Pulinilkunnil T, Nagendran J, Young ME, Bogner-Strauss JG, Hackl H, Khadour R, Heydari E, Haemmerle G, Zechner R, Kershaw EE, Dyck JR, (2013) Early structural and metabolic cardiac remodelling in response to inducible adipose triglyceride lipase ablation Cardiovasc Res. 99:442-51 
​
List of current research projects dedicated to CDG:
  • Development of a Zebrafish Disease Model for Congenital Disorder of Glycosylation Employing CRISPR/Cas9 Technology as a Foundation for Therapeutic Studies in Rare Disease Research. Thomas Pulinilkunnil PhD, Petra Kienesberger PHD, Lester Perez PhD, Duncan Webster MD.

List of current grants focused on CDG:
  • Grant for laboratory research technician through Foundation Glycosylation.

Well known professionals in the field of CDG are involved in this project: 
  • Pf Dr Jaak Jaeken (Center for Metabolic Diseases, KU Leuven, Leuven, Belgium).​

Vanessa Ferreira

About:
Email: sindromecdg@gmail.com
From her unique perspective of being a sister of a patient with a rare disease named Congenital Disorders of Glycosylation (CDG) and Cell Biologist, Vanessa founded the Portuguese CDG Association and other Rare Metabolic Disorders (APCDG-DMR). ​​

Vanessa’s personal journey with her sister, combined with the community needs, have been the impetus to focus the APCDG activities.
​Vanessa received a bachelor’s degree in Biological Sciences from Badajoz University (Spain). She holds a PhD (Sc.D.) in Cell and Developmental Biology from the Center for Genomic Regulation, University of Pompeu Fabra, Biomedical Research Park in Barcelona (PRBB). In 2014, she completed her background with an International MBA from IAE de Paris, Sorbonne Graduate Business School.

The faces of CDG researchers involved in the project
​“Heart involvement for CDG”

Pf Duncan Webster

Pf Jaak Jaeken

 Rita Francisco

Dorinda da Silva
Professor Duncan Webster
Email: duncan.webster@horizonNB.ca
Duncan graduated from Mount Allison University in 1993 with a BSc in chemistry, biology & physics as well as a BA (honours) in philosophy and religion. He completed his Masters degree in philosophy at the University of New Brunswick in 1998 and graduated from Dalhousie University Medical School in 2001. He completed his Internal Medicine residency training and Infectious Diseases fellowship at the University of Alberta before returning to Dalhousie for Medical Microbiology fellowship training which he completed in 2007.
​
​ He is an associate professor with Dalhousie University and an active teacher with the Dalhousie Medical School. He has numerous research interests and peer-reviewed publications and received the AMMI Canada Dr Juan A. Embil Award for Excellence in Infectious Diseases Research in 2006. He was awarded the Dalhousie Medicine Asclepian Torch Award in recognition for outstanding clinical teaching in 2012. For his innovative work in Infectious Diseases, Duncan was awarded the Dalhousie Medical Alumni Association Young Alumnus of the Year Award in 2012. In 2011, Duncan and his family established Foundation Glycosylation (the FoG) in order to support research for the development of therapies targeting CDG, to help raise awareness of the disorder and to advocate for individuals living with this enzyme deficiency. With this work he is collaborating with researchers at Dalhousie University and was awarded the Tim Cameron Big Heart Award in 2013.

The list of the 6 publications with a major impact for CDG research: 
  1. H Li, S Jean, D Webster, GA Robichaud, L Calhoun, JA Johnson, CA Gray. Dibenz[b,f]oxepin and Antimycobacterial Chalcone Constituents of Empetrum nigrum. Journal of Natural Products 2015;78(11):2837-40.
  2. T ONeill, H Li, C Carpenter, JA Johnson, D Webster, C Gray. Optimisation of the microplate resazurin assay for screening and bioassay guided fractionation of phytochemical extracts against Mycobacterium tuberculosis. Phytochemical Analysis 2014;25:461-7.
  3. D Webster, I Umar, G Kolyvas, J Bilbao, MC Guiot, Y Qvarnstrom, K Dupliseam, GS Visvesvara. Treatment of Granulomatous Amoebic Encephalitis with voriconazole and miltefosine in an immunocompetent soldier. American Journal of Tropical Medicine & Hygiene 2012;87(4):715-718.
  4. D Webster, Y Li, N Bastien, R Garceau, T Hatchette. Oseltamivir-resistant Pandemic H1N1 Influenza .Canadian Medical Association Journal2011;183(7):E420-2. 
  5. D Webster, B Lee, A Joffe, W Sligl, D Dick, A Grolla, H Feldmann, W Yacoub, K Grimsrud, D Safronetz, LR Lindsay. Cluster of cases of hantavirus pulmonary syndrome in Alberta, Canada. American Journal of Tropical Medicine and Hygiene 2007;77(5):914-8.
  6. D Webster, RP Rennie, CL Brosnikoff, L Chui, C Brown. Methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Canada. Diagnostic Microbiology and Infectious Disease 2007;57:177-81.​
Pf Jaak Jaeken
Professor Jaak Jaeken received his M.D. degree from the University of Leuven in 1967.  From 1967 to 1973 he trained in paediatrics at the same university. Subsequently he completed a research fellowship in metabolic diseases at the University of Zürich.

In 1975 he returned to Leuven. The contribution of Prof. Jaeken to medicine is exceptional, mainly in the field of metabolic disorders, due to the princeps-description of several metabolic diseases. In 1980, Prof. Jaeken was the first to describe  patients with a congenital disorder of glycosylation (CDG). He received his Ph.D. in 1985. In 1999 he received the degree of Doctor Honoris Causa from the University of Zürich, and in 2000 from the University of Havana. Since 2006, he is Emeritus Professor at the Faculty of Medicine. Prof. Jaeken is currently on the the Editorial Board of The Journal of Inherited Metabolic Disease (since 1994) and of Brain & Development (since 2004). He is a member of numerous societies and councils and he has received many prizes and honours. Prof. Jaeken’s publication list includes 517 papers, including 339 peer reviewed international publications, 2 books, 32 book chapters. He was guest editor of 2 special volumes on CDG. He hopes to continue working in the CDG field. He is an inspiration for the CDG community.

The list of the 6 publications with a major impact for CDG research: 
  1. JAEKEN J, VANDERSCHUEREN-LODEWEYCKX M, CASAER P, et al. Familial psychomotor retardation with markedly fluctuating serum proteins, FSH and GH levels, partial TBG-deficiency, increased serum arylsulfatase A and increased CSF protein: a new syndrome? Pediatr Res 1980; 14:179
  2. JAEKEN J, VAN EYCK HG, VAN DER HEUL C, CORBEEL L, EECKELS R, EGGERMONT E.  Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome.  Clin Chim Acta 1984;144:245-247
  3. JAEKEN J, SCHACHTER H, CARCHON H, DE COCK P, CODDEVILLE B, SPIK G.  Carbohydrate-deficient glycoprotein syndrome type II : a deficiency in Golgi-localized N-acetylglucosaminyltransferase II.  Arch Dis Child 1994; 71:123-127
  4. VAN SCHAFTINGEN E, JAEKEN J.  Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I.  FEBS Lett  1995;377:318-320
  5. JAEKEN J, Matthijs G, Saudubray J-M, et al.  Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation.  Am J Hum Genet 1998;62:1535-1539
  6. JAEKEN J, VLEUGELS W, REGAL L, et al. RFT1-CDG: deafness as a novel feature of congenital disorders of glycosylation (CDG). J Inherit Metab Dis 2009; 32:756-757
Rita Francisco:
Rita Francisco has a Masters’ degree in Molecular Genetics by the University of Minho and among her main scientific interests are genetic disorders. In 2016, she was awarded the 3rd Liliana Scientific Scholarship. In March 2017, she won a PhD scholarship awarded by Fundação para as Ciências e Tecnologias (FCT) and she is now dedicating herself to unravelling the immunological aspects of CDG. Rita is highly driven and motivated to make a difference in the lives of adults and children living with Congenital Disorders of Glycosylation (CDG). Her work is developed under the scope of the CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies – PPAIN). In addition, she is our  CDG patient advocate manager and CDG International Patient Relations.
Dorinda da Silva
Dr da Silva, received her Biochemistry degree in University of Algarve – Faro, Portugal. She defended her PhD thesis on ​“Study of redox and calcium transport systems microdomains in the plasma membrane of neurons”, in University of Extremadura – Badajoz, Spain. Her work is developed under the scope of the CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies – PPAIN). She integrated our working group since beginning February 2016. Dr Dorinda is highly motivated to make a difference in patients lives.

Open position!

Inés Summer Internship CDG for Undergraduate Students:
Currently the WP2 expressed interest in hosting a student to conduct summer research focused on diagnosis for CDG.
​This position is available under the scope of the “1st Inés Summer Internship CDG Program for Undergraduate Students”. 

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