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French version - version française
Newsletter Winter 2002-03
We've moved again!
Please use the attached updated membership form with the correct address information to send in dues or donations.
Thank you.
Our New Address is:
Canadian VHL Family Alliance
c/o Jill Shields, 4227 Hamilton Road
Dorchester, ON Canada N0L 1G0
Tel: (519) 268-1567
When sending in membership renewals, please use the complete name"Canadian VHL Family Alliance"on all
envelopes, as this name is registered with Canada Post. We unfortunately are unable to process credit card
donations at this time.
Welcome and hello again!
First, warm thanks to all members who renewed their memberships and sent in memorial donations. Secondly,
this newsletter is an ideal forum to advise you of some of our accomplishments and future plans. Your Board has
been very busy in the past year.
Accomplishments for 2001/2002
- Attended Patient Care / Provider meeting at Stanford University, Palo Alto, CA.
- Organized transition meeting in Ottawa with past Director, Tania Durand.
- First Board Meeting held in September.
- Contacted database business to select format-friendly membership information-tracking software.
- Second Board Meeting held in October.
- 31 October is our year-end. Collected all information and compiled financial and income statements to meet all legal obligations.
- Third Board Meeting held in November.
- Fourth Board Meeting held in December.
- Met with Vice-President External at RRI to explore fundraising avenues. Referred to Big Database Online.
- Contacted Canadian Genetic Network to include link to our site.
- Investigated, then purchased membership in Big Database Online.
- Set up Chapter Chair in Northern Alberta.
- Communication with Minister of Health re wait lists for patients needing genetic testing and costs incurred for samples sent to our DNA centre in Halifax.
- Follow-up with Minister in January.
- Attended planning meeting in Nashville with US Board of Directors in February.
- Discussions with Director of Clinical Trials re VHL trials in Canada.
- Dr. Joe Verdi invited to assume Research Director position with US Board.
- Met all end of April government requirements, including income tax.
- Attended Canadian Alliance of Brain Tumour Organizations (CABTO) meeting in May in Montreal, QC to share information on VHL with specialists.
- Attended CABTO Board meeting, formed partnership with Brain Tumour Foundation of Canada for information sharing with physicians and patients.
- Further follow-up with Minister re OHIP and genetic testing; finally received a reply.
- Received five grant applications for review by Dr. Joe Verdi.
- Ongoing correspondence with VHL membership.
- Recruitment of additional Board member, Barbara Lowery, to assist with grant writing and development (see bio).
- Contacted Employee Charitable Contribution Organization (ECCO) of the London Health Sciences Centre, requesting VHL is added to list of charities for employee donations.
- Bell Canada set up to receive donations for VHL.
- In memoriam donations.
- Visit to Nova Scotia to talk with VHL membership in the Maritimes. Used personal vacation time.
- Conference Call of Chapter Chairs and Board Members in June.
- Strategic Planning session in July.
- Visited members of CVHLA in August.
- Board meeting in September with heavy agenda, including addition to the Board of Stephen Pautler, MD (formerly US NCI, with considerable VHL expertise; see bio).
- Membership Newsletter and mailing in October.
Future Planning:
- As a member of CABTO, explore possibility of setting up a registry in Canada to collect information on all benign and malignant brain tumours.
- Mass mailing to all doctors across Canada regarding VHL.
- Organizing National meeting in 2003.
- Ongoing Board meetings twice a year or more as required.
- Attending Patient Care Provider meeting in Cleveland, October.
- Attracting more medical personnel to Board of Directors.
- Fundraise, fundraise, fundraise!
- Establishment and maintenance of ongoing media contact.
- Enhanced Canadian content on VHL website.
- Create a Clinical Centre of Excellence in London, Ontario, for VHL disease
Our ultimate goal is to find a cure for this disease.
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- Exciting News for the Canadian Alliance
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Introducing our newest Board members...
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Much to our delight, The Canadian von Hippel-Lindau Family Alliance recently became aware ofDr. Stephen Pautler, a VHL specialist who joined The University of Western Ontario's Division of Urology in London, Ontario this year. While completing a degree in Chemistry at the University of Waterloo, he worked at Sick Kids Hospital in Toronto and participated in gene mapping research for the gene that causes a copper metabolism disorder called Wilson’s Disease. Following UW, he graduated from the University of Calgary Medical School in 1995, subsequently completed a urology residency at Western, and became a Fellow of the Royal College of Physicians and Surgeons of Canada in 2000. |
Barbara Loweryalso joins our Board of Directors, bringing considerable experience to the Board in many forms. She's Agency Principal of The Wordsmith, founded in Vancouver in 1996 to provide writing and editing services to clients across Canada and internationally. She mentors in the federal government's Self Employment Programs in BC's Lower Mainland, helping new entrepreneurs take their first steps in creating a marketable image for a successful launch into today's tough business world. She's also been involved in some aspect of the academic world (science, medicine and social science) for more than 35 years, including extensive periods as administrative support in Western's Reproductive Biology Research Laboratories and currently in the Cancer Research Laboratories of the London Regional Cancer Centre. Barbara brings communication skills and fundraising expertise to our Board.
Asked why she so willingly jumped in, Barbara explains:"I'm a survivor of ovarian cancer, and I know how cancer affects the spirit, understand some of how it affects the body, have felt the impact of the disease on a family. I've lost people I love to cancer, and I know that loving them doesn't stop. So this is one of the things I can do in tribute. Knowledge is empowering, and communication conveys that knowledge. When I see something as valuable as the Canadian VHL Family Alliance, see the dedication on this Board and understand the effort involved, how can I say anything but an enthusiastic yes? One person does make a difference, and I can help communicate not just the knowledge but the growing sense of hope and optimism we're feeling, as research really moves closer to the bedside to help the clinician help the patient–new and gentler options in treatment methods, how to optimize those methods, how the VHL patient and the treatment team work together. We're learning so much, and we're all in this together. There's an optimism that can't be beaten down and a power that's unstoppable."
VHL patient, clinician, researcher work together as a team–and underlying them all is the support of a talented and dedicated Board and Membership committed to an improved quality of life and an increased knowledge and awareness. If you have talents you're willing to share, please contact us. Many hands working together make light work of a heavy load.
Call for Volunteers
As with any not-for-profit organization, the wonderful people who freely volunteer their spare time to promote the awareness of VHL power our accomplishments. Thank you! Volunteers are required at every level of this organization, and there's no task too big–or too small. We need you: to head a Newsletter Committee; help organize a National meeting; stuff envelopes; become a Chapter Chair for your province; set up support groups; spread the word about VHL. Please let us know if you'd like to contribute your expertise to the Alliance.
Did you know? Board members, who are all volunteers, absorb most operating and travel expenses. We also use our personal vacation time from our regular, full-time occupations to travel on behalf of our membership. And we do a lot -- set up Chapter Chairs, attend meetings to disseminate information, attract knowledgeable medical personnel for membership referral, contact members by phone / email, purchase office supplies, etc., etc.
The majority of our membership fees and donations go to our US Affiliate to defray costs of mailings, printing of brochures, website maintenance and, of course, research. Last year, we contributed $2200 US to our head office in Brookline, MA. Those funds came from membership fees and a golf tournament fundraising effort by Susan Lamb, our Board Member in charge of fundraising. How can you help? Donations of dollars are always welcome, but you can help by being a volunteer. Hold a fundraising event–Susan can assist with the planning, and with ideas. Large or small, every effort counts. Thanks for helping.
Canada to Host the Patient / Care Provider Conference in 2003
We're proud and excited to host the 2003 Patient / Care Provider Conference here in London, Ontario. Under the guidance of Dr. Stephen Pautler, we will bring renowned medical experts to speak at the Conference and share the progress being made in treatment, research and quality of life for VHL patients. Watch for a new website with program, registration, and accommodation information. This will be a unique opportunity for Canadians to meet and exchange information, while we make steady progress in medical research into VHL. We'll keep you posted.
| The Canadian meeting, previously announced for Ontario, May 2003, has been cancelled. Efforts are under way to plan a more modest regional meeting late in 2003. Volunteers are needed to assist with planning and organizing the meeting. Please contact Jill or Sue at canada@vhl.org or 519-268-1567 to offer your help. |
Research News
Joseph Verdi, Ph.D., one of our Directors, recently accepted an invitation to assume the position of Research Director for our US affiliate. Joe takes over the reins from Dr. Myriam Gorospe, who so competently filled that role for over three years. Our heartfelt thanks to Myriam for the wonderful job she did in funding VHL researchers.
Joe also recently relocated to the Maine Medical Center Research Institute in Portland, Maine. We'll miss his smiling face here in London, but appreciate that he's continuing to play a role on our Board. Joe and his family are getting settled in Falmouth, Maine. Congratulations, Joe!
Profiling Canadian Research…
As awareness of VHL increases in Canada, we're attracting many high-profile excellent researchers into the field. Dr. Stephen Lee in the Dept. of Cellular and Molecular Medicine at the University of Ottawa is a well-known Canadian researcher working on the Functional Characterization of the von Hippel-Lindau Tumor Suppressor Gene Product.
Functional Characterization of the von Hippel-Lindau Tumor Suppressor Gene Product
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The von Hippel-Lindau (VHL) tumor suppressor gene was isolated in 1993 as the gene that causes the inherited VHL cancer syndrome. Individuals afflicted with VHL disease are at high risk to develop multiple, highly vascularized, tumors of the kidney, brain and eye. VHL patients inherit at conception a mutated, inactivated allele of the VHL tumor suppressor gene. Tumors arise in susceptible cells when the remaining wild-type copy of VHL acquires a somatic mutation, in keeping with Knudson's"two-hit"hypothesis of tumor suppressor genes (Fig. 1A). Biallelic inactivating mutations of the VHL gene are also found in sporadic clear cell renal cell carcinoma (RCC), the most common and deadliest form of kidney cancer in human (Fig. 1B). Approximately 12,000 Canadians suffer from RCC, another 4,000/year will be diagnosed with RCC and 1,100 will die this year alone of this disease. RCC is in dire need of fresh therapeutical approaches since patients are ultimately refractory to traditional chemical- and radiological-based therapies and generally have a bleak prognostic.
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The VHL tumor suppressor protein. VHL is a small protein of 213 amino acids that forms a complex with four other proteins referred to as elongin B, elongin C, cullin-2 and rbx-1 (VBC/Cul-2). This complex displays E3-ubiquitin ligase activity, targeting specific proteins for poly-ubiquitination and subsequent degradation by the 26S proteosome. The alpha subunits of hypoxia-inducible factor-1 (HIFa) are known substrates of VHL-directed ubiquitination and degradation. HIFa are constitutively degraded by the VHL complex in normoxia but stabilized by hypoxia. Once stabilized, HIFa assembles with HIFb to form the HIF transcription complex, which activates HIF-1 inducible genes such as the one coding for the angiogenic vascular endothelial growth factor (VEGF). VHL-/- RCC fail to degrade HIFa leading to a constitutive overexpression of HIF-regulated genes, which likely explains the highly vascularized nature of VHL-/- RCC and other VHL tumors.
Activation of a TGF-a/EGFR autocrine circuit as the gatekeeper that promotes tumorigenesis in VHL-/- RCC. My laboratory as focused on understanding the mechanisms involved in tumorigenesis upon the loss of VHL function in renal epithelial cells. As mentioned above, HIF-regulated genes are activated in VHL-/- RCC cells irrespective of oxygen tension. One such activated genes is the one coding for the angiogenic transforming growth factor-a (TGF-a). In contrast to VEGF, TGF-a can also act as a growth stimulatory molecule for renal epithelial cells. According to our model (Fig. 2), VHL-/- RCC cells engage in a TGF-a/epidermal growth factor receptor (EGF-R) autocrine loop, which just might be the event that initiates tumorigenesis. We believe that this is the"Achilles' heel"of human RCC since there are several drugs available that specifically inhibits EGF-R-mediated signaling. My laboratory is focusing its efforts toward better understanding the role of the TGF-a/EGF-R autocrine loop in VHL-/- RCC, which looks promising as a potential target for treatment of patients afflicted with RCC (Fig 2).
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VHL engages in a novel nuclear/cytoplasmic transport pathway. An emerging concept in ubiquitin-mediated degradation of proteins is that E3-ubiquitin ligase must traffic between the nucleus and the cytoplasm to degrade their respective substrates (see"moving protein heads for breakdown"Nature (1999) 398:103 for a good review of this hypothesis). In an effort to understand the function of the VHL tumor suppressor protein, my laboratory has stumbled on what appears to be a novel nuclear/cytoplasmic trafficking pathway utilized by VBC/Cul-2. The goal for the near future will be to delineate this intracellular transport pathway and understand its relationship to the ability of VHL to function as an E3-ubiquitin ligase and to mediate oxygen-dependent degradation of HIFa.
Position availability.Members of my laboratory are part of a multi-discipline team involved in the functional characterization of the VHL tumor suppressor gene product. Students and post-doctoral fellows are trained in protein biochemistry, cell biology and molecular biology techniques to answer fundamental questions in modern molecular oncology.
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RECENT RELEVANT PUBLICATIONS
Gunaratnam, L., Franovic, A., de Paulsen, N. and Lee, S. Hypoxia-inducible factor-mediated overexpression of transforming growth factor-alpha is the major oncogenic determinant of VHL-/- renal cell carcinoma. (In preparation).
Groulx, I. and Lee, S. (2002) Oxygen-dependent ubiquitination/degradation of hypoxia-inducible factor requires nuclear/cytoplasmic trafficking of the von Hippel-Lindau tumor suppressor protein. Mol. Cell. Biol. 22:5319-5336.
De Paulsen, N., Brychzy, A., Fournier, M.-C., Klausner, R. D., Gnarra, J. R., Pause, A., and Lee, S. (2001) Role of TGF-a in von Hippel-Lindau (VHL) -/- clear cell renal carcinoma proliferation: A possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis. Proc. Natl. Acad. Sci. USA 98:1387-1392.
Bonicalzi, M.-E., Groulx, I., de Paulsen, N. and Lee, S. (2001) Role of exon 2-encoded b-domain of the von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. 276:1407-1416.
Groulx, I., Bonicalzi, M.-E., and Lee, S. (2000) Ran-mediated nuclear export of the von Hippel-Lindau tumor suppressor protein occurs independently of its assembly with Cullin-2. J. Biol. Chem. 275:8891-9000.
Lee, S., Neumann, M., Stearman, R., Stauber, R., Pause, A., Pavlakis, G. N., and Klausner, R. D. (1999) Transcription-dependent nuclear-cytoplasmic trafficking is required for the function of the von Hippel-Lindau tumor suppressor protein. Mol. Cell. Biol. 19:1486-1497.
Pause, A.*, Lee, S.,* Lonergan, K. M., and Klausner, R. D. (1998) The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal. Proc. Natl. Acad. Sci. USA 95:993-998.
*Equal contribution.
Michael Ohh, PhD,Canada Research Chair in Molecular Oncology and Assistant Professor, University of Toronto
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Dr. Michael Ohhreceived his doctorate from the University of British Columbia, and was a Medical Research Council and National Cancer Institute of Canada postdoctoral fellow at Harvard Medical School in the Department of Adult Oncology, Dana-Farber Cancer Institute prior to joining University of Toronto. Dr. Ohh holds the honour of Canada Research Chair in Molecular Oncology. |
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Michael explains his work:"My laboratory is focused on defining the molecular mechanisms of cancer. Growing tumours inevitably face oxygen and nutrient crises. To overcome these challenges, neoplastic cells initiate the hypoxic response and trigger neovascularization or angiogenesis (i.e., new blood vessel formation). In fact, angiogenesis is a cardinal feature of solid tumours, and clinical studies are currently under way to examine the effectiveness of drugs that block angiogenesis in treating cancer patients. Recently, we have discovered that a protein (pVHL) encoded by the von Hippel-Lindau tumour suppressor gene targets hypoxia-inducible factor (HIF), which is a master transcription factor that governs the expression of hypoxia-inducible genes, including those that regulate angiogenesis. Specifically, pVHL complex tags HIF with a polyubiquitin chain, which marks HIF for destruction by the 26S proteasome. Individuals with mutations in the VHL gene fail to target HIF for destruction and consequently express inappropriately high levels of hypoxia-inducible genes, and invariably develop tumours in multiple organs (including brain, spinal code, eye, inner ear, adrenal gland, and kidney). Our research objective is to further elucidate the mechanisms that control the tumour suppressor function of pVHL with the supposition that the lessons learned from our studies will aid in the development of novel anti-cancer therapies."
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It's encouraging to see our Canadian granting agencies funding VHL research and researchers likeMichael OhhandStephen Lee, all interested in finding cures for people with VHL. Keep up the good work!
CABTO: What is it?
The CVHLFA is proud to be a member of CABTO, Canadian Alliance of Brain Tumor Organizations. The Canadian Alliance of Brain Tumour Organizations (CABTO) is an alliance of volunteer organizations, formed in 1999 and dedicated to enhancing the quality of life of brain tumour patients and their families. Our mandate is to advocate for better patient care and increased funding for research. Member organizations believe that by working together, we can accomplish these goals more effectively than by working alone. Currently, we are lobbying governments to increase funding for brain tumour research, to reduce radiation waiting lists, and for accurate and complete collection of statistics.
Celebrate Brain Tumour Awareness Month
October is Brain Tumour Awareness Month. So what does this really mean? For individuals and families living with a brain tumour, it's an opportunity to get support and information. Across Canada, member organizations of the Canadian Alliance of Brain Tumour Organizations, support groups, cancer centres and hospitals are talking about brain tumours and hosting events to raise awareness about this often devastating disease.
Join us! You'll find out about new research and treatments, and maybe even make a new friend. Get support, celebrate life, share your hope.
Canadian Alliance of Brain Tumour Organizations Members
- Acoustic Neuroma Association of Canada
- B.r.a.i.n.child (Maritimes)
- B.r.a.i.n.child (Toronto)
- Brain Tumour Foundation of Canada
- Canadian Association of Neuroscience Nurses
- Canadian Von Hippel-Lindau (VHL) Family Alliance
- Candlelighters Childhood Cancer Foundation Canada
- Crolla Family Brain Tumour Research Centre
- Epilepsy Canada
- Gerry and Nancy Pencer Brain Trust
- Montreal Neurological Hospital, Centre for Treatment and Study of Brain Tumours
- North American Brain Tumor Coalition
Financial Reporting and Accountability
On the following two pages you will find the Financial Reporting for the Canadian VHL Family Alliance. Included is the Balance Sheet and Income Statement from November 1, 2000 to October 31, 2001.
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Canadian VHL Family Alliance
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Balance Sheet as at 10/31/01
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ASSETS
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Current Assets
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Bank of Montreal
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6,702.54
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Total Cash
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6,702.54
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Total Receivables
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0.00
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Total Current Assets
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6,702.54
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Capital Assets
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Net Computer Equipment
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0.00
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Total Capital Assets
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0.00
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Other non-Current Assets
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Total Other Non-Current Assets
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0.00
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TOTAL ASSETS
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6,702.54
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LIABILITIES
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Liabilities
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GST Owing (Refund)
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0.00
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Total Liabilities
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0.00
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TOTAL LIABILITIES
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0.00
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EQUITY
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Surplus (Deficit) of Funds
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Surplus (Deficit) Previous Year
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831.61
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Current Earnings
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5,870.93
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Total Surplus (Deficit) of Funds
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6,702.54
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TOTAL EQUITY
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6,702.54
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LIABILITIES AND EQUITY
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6,702.54
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Canadian VHL Family Alliance
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Income Statement 11/1/00 to 10/31/01
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REVENUE
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Revenues
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Membership Fees
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605.00
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Donations
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5,565.48
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Net Revenue
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6,170.48
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Other Revenues
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Total Other Revenues
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0.00
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TOTAL REVENUE
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6,170.48
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EXPENSE
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Expenditures
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Photocopy
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49.68
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Postage
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160.27
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Supplies
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45.74
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Interest and Bank Charges
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26.45
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Miscellaneous
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17.41
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Total Expenditures
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299.55
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TOTAL EXPENSE
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299.55
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NET INCOME
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5,870.93
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Our thanks for donations from:
Donor:
Eva Antonescul, in honour of Christine Antonescul
Roger Potvin, in honour of Tania Durand
Mary Dora Gylland, in honour of Annie Gylland
Wendy Suzanne Hatfield, in honour of Clifford Hatfield
Stan Russell, in honour of Alyson Russell
Adriana E. Aartsen in honour of Brent and Devon Lamb
Brickhouse/Abars Golf Tournament
Carol Derbyshire
Grayon Industrial Products Inc.
Sylvia Honselaar
Victor Klepeckas
Linda&Alan McLeod
Rob MacPherson
Motor City Community Credit Union
John&Edith Taylor
Margaret&Les Taylor
Karen Wild
Woodall Construction Co. Ltd.
Mr. And Mrs. James Karoulis, in honour of Richard MacDonald
Louise Blanchard, in honour of Francine Desrosiers
Joanne Desrosiers, in honour of Jean Francois Desrosiers
Joanne Desrosiers, in memory of Francine Desrosiers
Carl and Sheila Johnson, in memory of Mary"Paula"McNair
Eunice M. Halen, in memory of Mary"Paula"McNair
Elisabeth Spronken, in memory of Mary"Paula"McNair
Miss Bernadette Vangool, in memory of Mary"Paula"McNair
Joy Weir, in memory of Mary"Paula"McNair
Rick&Nancy Bondy, in memory of Mrs. Steriani (Stella) Stogiantsis
Ben&Maria Crolla, in memory of Mrs. Steriani (Stella) Stogiantsis
Clarence&Veronica Sinasac, in memory of Mrs. Steriani (Stella) Stogiantsis
Tony Teti, in memory of Mrs. Steriani (Stella) Stogiantsis
Bruna Verro, in memory of Mrs. Steriani (Stella) Stogiantsis
We would like to recognize all donations and apologize if you have not received anIn Memoriamacknowledgment card from the CVHLFA; please emailjill@robarts.ca. Our thanks!
Click here for the Membership Form
Thank you for your support.
Directors and Chapter Chairs |
