ALZHEIMER RESEARCH LABORATORY
DR. A. CLAUDIO CUELLO
Professor and Charles E. Frosst Merck Chair in Pharmacology
SEPTEMBER, 2009
Back Row: Simon Allard, Aaron Hackett, and Dr. Alan Frosst
Front Row: Dr. Wanda Leon, Adriana Ducatenzeiler, Tizian Melis, Dr. Claudio Cuello, Florencia Iulita, Maria Teresa Ferretti, Luisa Pimentel, Dr. Fabio Canneva
In September, it was my distinct pleasure to visit once again with Dr. Claudio Cuello and his research group in McGill University’s Department of Pharmacology. The group is vibrant in its research efforts to understand and hopefully develop medical treatment for the debilitating Alzheimer’s disease (AD). The support by the Frosst family with Merck Frosst Canada in the endowment that funds the Research Chair for Dr. Cuello and the Postdoctoral Fellowshp that provides the fundingfor Dr. Fabio Canneva is appreciated greatly by the team.
Dr. Canneva joined the group in June, 2007, following the establishment of the PDF position, and he brought with him significant experience and knowledge in the field of molecular biology. His contributions have been numerous, the most important resulting in recognition for the group with the presentation of the JWS-CNS Research Award for AD/PD 2009 (Alzheimer’s Disease/Parkinson’s Disease). We have certainly been proud that he has been the initial recipientof the Charles E. Frosst Merck Postdoctoral Fellowship.
- 2 -
The visit to the Department of Pharmacology was greeted with the plaque commemorating the establishment in 2004 of the Chair that supports Dr. Cuello. This is displayed prominently in the hall, adjacent to the access to the pharmacology research floor in the McIntyre Building. There is great pride within the Faculty of Medicine of this Chair, and efforts have been underway using this as amodel to develop similarly family/industry-funded Chairs.
In appreciation of my expected visit, Dr. Cuello’s group met in the summer for a deck party at Claudio’s home and constructed a welcoming sign.This was greatly appreciated. Later, the Group presented a formal tribute to the Frosst Family.
The visit started with a session with Ph.D. student Simon Allard, who treated me to a wonderful demonstration of the powerful use of the electron microscope. Samples of brain tissue harvested from rodents as well as from human donors are investigated microscopically to detail and understand the pathology of the disease.
- 3 -
There is great delicacy in preparing the samples for the electron microscope.Elucidation of the toxic peptide – amyloid-β peptide (Aβ) -as shown in this slide is essentialforimproved understanding about the progress of the disease.
When the group met as a whole to share with me some of the research advances, Claudio commenced with a whiteboard review of the progress of Alzheimer’s disease and initial cognitive impairment. He showed slides of the cortical cholinergic system and discussed the various approaches researchers are using to investigate this disease. The early events in the AD pathology, from the aggregation of soluble Aβ to the rise of neurotoxicity, are still poorly understood.
- 4 –
Dr. Fabio Canneva, Frosst Merck PDF, then illustrated some of the findings about the physiology and pathology of the Aβpeptide and how the amyloid plaque develops with its debilitating result. The molecular biology involved in this understanding is at the forefront, and we have been so fortunate to have had Dr. Canneva’s involvement. Unfortunately, he will leave the group to return to Italy in May, 2010. Now, plans are underway to attract another top-flight PDF for the second half of the initial five-year funding.
Dr. Canneva’s achievements with the model transgenic rats are marvellous, and he, along with Dr. Wanda Leon, were commended for their success in developing this model. The McGill–Thyl-APP transgenic mice-over-expressing the human amyloid precursor protein (APP) accumulate Aβ intracellularly in cortex and hippocampus as early as one week of age and start depositing amyloid plaques at four months of age. Behavioural deficits are observed at three months, permitting early research about the various impacts of the disease.
Dr. Wanda Leon has worked diligently on the cholinergic neuron involvement in AD. She is a medical doctor from Venezuela working in the final preparation for the Ph.D. Shortly, she will present and defend her thesis.
Maria Teresa Ferretti’s work on early pro-inflammatory processes is most interesting when the Tg mice show the first cognitive deficits. Earlier in her studies, she was awarded the one-year Frosst Foreign Studentship that Uncle Alec created many years ago. Maria Teresa is from Sardinia and this is a rare opportunity for a young woman to study abroad.
Maria Teresa’s investigation on the early, pre-plaque inflammatory process in AD-like transgenic models and the neurotoxic effects of Aβ-oligomers and pro-inflammatory responses could elucidate possible arresting processes. She currently holds the Principal’s Graduate Fellowship.
There are four new students in this group. Aaron Hackett (McMaster University), Florencia Iulita (transferred from Masters to Ph.D. studies), Luisa Pimentel (Ph.D. student, arrived with a Masters degree in Pharmacology from Rio de Janeiro), and TizianMelis (exchange student from Cagliari University, Italy) have commenced studies toward graduate degrees. Interestingly, while their association with Claudio has not been very long, each has already participated in publication. This is commendable for the viable relationship within the group andspeaks highly about the leadership provided to these young people.
Florencia and Luisa joined with Dr. Wanda Leon for happy smiles. I look forward to future visits to hear about their research activities toward their graduate degree goals.
- 5 -
Not a visit goes by without being impressed with the many years of contribution that Adriana Ducatenzeiller has provided as Senior Technician and Laboratory Manager. Her untiring efforts and technical support over so many years have been invaluable. Certainly, her participation must return to her great joy as she has witnessed the research advances and seen researchers mature and graduate from McGill. I have mentioned that she should prepare a scrapbook about all those fortunate persons who have been within her ‘care’.
Thank you, Adriana.
At the conclusion of the day, Claudio and his group presented to me a bound volumeof the recent publications, along with their thanks and notes of appreciation expressed in the introductory pages. This was a wonderful present to receive.
Their tribute to the involvement of and support by the Frosst family was identified clearly by the individual expressions of thanks.
In particular, Dr. Canneva’s personal comment and sincere appreciation for the opportunity to work in such a nourishing scientific environment speaks enormously about the success of the Charles E. Frosst Merck Postdoctoral Fellowship programme.
Last February, Dr. Cuello addressed The Whiff of Grape in Toronto and drew a wonderful audience and response to his informative and delightful presentation. In recognition of that occasion, the book presentation included pictures from that evening. Claudio brought along his commemorative ‘cannon’ to share his memory of that event in Toronto.