Update from Dr. Eric Hoffman on research funded by the Crystal Ball 2002
Marina has undertaken a large study to determine if we can provide answers to the hundreds of patients that are given ambiguous diagnoses. This involves the attempt to do "diagnosis by chip", where we first create a huge data warehouse of genome-wide expression profiles of all the known causes of muscular dystrophy (use of just available U133 arrays covering the entire human genome on two small areas of glass). We then float the expression profiles (genechip data) from "unknown" patients (such as your son) across the data warehouse to see if it matches any known dystrophies, and, if not, what is uniquely changed with the muscle that implies a novel diagnosis. This research has direct implications for therapeutics as well. There is a major effort to define the "pathways" that cause a muscle disease to be progressive, and target therapeutics towards stopping these pathways. This is already well underway for Duchenne dystrophy, but your fund-raising has made the first attempt for this for limb-girdle dystrophy possible. I should emphasize that all data will be made publicly available, through public access web interfaces with our data warehouse.

The scientist dedicated full time to this project is Marina Bakay, PhD, one of the most experienced people in my large laboratory. Your support provides her post-doctoral fellowship salary (about $40,000/yr (plus benefits), which is quite inexpensive considering her extensive training and expertise! a deal!), and all the expensive genechip reagents (it costs about $1,300 per muscle biopsy for just materials for the profiles, and she must generate many dozens of profiles). She is currently analyzing 5 Duchenne dystrophy biopsies, 5 Becker dystrophy, 5 dysferlin deficiency, 3
Calpain deficiency, 5 FKRP deficiency ($30,000 in chips and chemicals). The funding will also help provide computer support for the analysis of the data, and generation of new programs to interpret and develop the "diagnosis by chip" algorithms.

Over the last two months, she has identified all the biopsies she will test (from our 4,000 biopsy tissue bank), and has begun preparation for all the genechips. She has also published a paper in Neuromuscular Disorders finishing her previous work, which was a 40 chip whole-genome assessment of expression profiling in normal muscle, and Duchenne dystrophy muscle (using previous generation genechips).

Dr. Eric Hoffman

Crystal BAll 2003 update on research from Dr. ERic Hoffman
Making major progress, and expanding the team considerably. As I think I mentioned, thanks to the Crystal BAll's support last year, Marina was successful in getting an MDA grant to cover most of her salary. This freed up your funding to hire 50% of a bio-informatics PhD from Catholic University that
just graduated (Zuyi Wang) to work on the data set and clustering. This will help analyze all the data.

We are also having a Dutch student come and work for 6 months or so, and i'm assigning her to this project as well. Forget her name, but she comes next week. She is free! I guess the Dutch government helps fund her.

Finally, there is a good Argentinian MD who has been working in the lab for about 3 months for free, Gisella. She just got married and her husband is moving to Ohio for work, but she is willing to work here for 9 months if I get her a visa (and pay her a bit). I can get the Visa off of my hospital funds. She would round out the limb-girdle team (and bring the effort from Marina to four people to really push things forward), and would only cost about $30,000 for 9 months. Do you think this is a good expenditure of your Safari funds?

we have built the data warehouse to the point that we have reasonable statistical power in it. what we are going to do now is float "unknowns" (such as your son) genechip profiles across the database, find specific pathways genes that are dysregulated, then sequence these genes to look for changes. Gisella would work on the chip and sequencing part.

Perhaps we can schedule a meeting up here sometime for you and Linda to meet all the new people?

Best regards,
Dr. Eric Hoffman