Later today I will be presenting a poster at the Days of Molecular Medicine Conference in Boston. Last year the DMM conference was at Karolinska, this year it is being held at the Mass. General Hospital, part of Harvard.
We haven't said much about Cancer on this study site, as it is such a hot potato for many of you, but I have been working in the background to better understand the disease mechanisms, and to get them to reconcile with the biological 'model' I have built of the Th1 inflammatory processes.
Maybe while at Mass General you will bump into the folks from CeDAR ( Center for D Activation Research) whose stated mission is "to support research and improve understanding of the widespread biological and clinical consequences related to the activation of the vitamin D receptor". They are affiliated with Mass General.
Thanks for the Flash version of the video, Wrotek.
Well, here I am at Harvard, meeting some very interesting people, and generally trying to learn anything I can learn from the conference attendees.
I can't help but be struck again, as I was at the Salk Institute conference on Diseases of Transcription in January, that nobody else here is using the new molecular tools, that 'wet Biology' is still touted as the standard, and that everybody's research is focused on producing 'the killer drug' rather than defining the cause of a condition. Hmmm...
Anyway, at least everybody agrees that murine models are of limited usefulness, and gene knockout mice are only useful to the extent we are able to define the gene's functions.
I was surpised that the keynote speaker, Ralph Weissleder from Harvard, was absolutely emphatic that research in cell lines can never replace in-vivo data, because the results can be completely different. That was a breath of fresh air.
So I will keep on plugging away... Two more days of presentations still to come...
Very disappointing to hear about the empahsis on 'killer drugs' and lack of interest in the 'cause of condition.' I have been wondering about the influence of bacterial infections on the role of epigenetic factors (e.g. loss of imprinting - LOI - due to hypo- and hyper-methylation of DNA) that are increasingly being implicated in inflammation and cancer (and of course, aging). A current review article in Nature highlighted the role of environmental toxins and dietary factors in LOI, but did not mention bacterial infection. A quick search in PubMed revealed studies implicating H. pylori infection with the development of gastric (and colon) inflammation and cancer, but little else. Have you become aware of new research in this area at the meeting?
Add that one to the list of reasons bugs are getting ahold of us. This is also a basic concept Dr. M has been telling us: "accumulation over a life time." Furthermore, HGT isn't just allowing abx resistance but virulence genes to mix too.
____________________ "Lyme","CFS", Meningitis
Phase3 8-2-07, MP on hold 11/2007
DMiller, Nobody from CeDAR is at the conference, nor have any of the delegates mentioned CeDAR to me. I wil try and make some phone calls this morning.
Ruth, LOI doesn't have to be mysterious when you consider the mutation and expression-changing-ability of the tens of thousands of genes belonging to the pathogens. I doubt that it is as simple as a 'mother' or 'father' imprint, though. Think about how easy it was for Medicine to grasp onto the (IMO faulty) concept of prions, yet how hard it has been for Medicine to recognize that Koch may have been wrong, and that chronic disease is far more complex, and in many ways beyond our control, than the pragma of the past have taught. Most of the people here are interested only in the cycle of applying for grants and then applying for more. Since grants are peer reviewed, you cannot get grants if you are way out in front of your field.
Look for example at Tony Norman's latest work, "IFN-gamma- and TNF-Independent Vitamin D-Inducible Human Suppression of Mycobacteria: The Role of Cathelicidin LL-37." http://tinyurl.com/22jmqr
and how basic it seems from our vantage point. Indeed, it is basic. Tony; who discovered 1,25-D; has long since failed to lead research in the field, and has no real concept of what we have been doing. I am sure that Tony feels that we are not 'thorough' enough - perception is all a matter of perspective and insight...
Wrotek, Yes, it takes hard work to understand what the molecular software can do, and to get useful results. I have several colleagues, including one from the Gromacs development team, who have helped me with insight from time to time.
Greg, that citation you give is instructive. You see, we are living in real time. In Internet time. If anybody, anywhere in the world, publishes a concept of interest to us we immediately know about it and add its insight to our pool of knowledge. This conference is co-sponsored by the Journal 'Nature Medicine,' and most of the delegates here are not interested in such 'anecdotal' sources as they rely on 'authority' of 'peer-reviewed literature.' The speakers are selected by Nature Medicine editors. The speakers for next year's conference have already been (largely) selected. In many ways it is all a lot of self-serving buddy-back-slapping. But our nation continues to pour research monies into the coffers of a system like this, and the nation is living out the results, or lack of results, which come from such poor methodologies.
So in many ways I am a pariah here - how dare I say I have a validated model for chronic disease! I have to seek out the folk who are still relatively untainted by the old-boys-club, such as the younger Nature editors here, and the post-Docs who will shape the next generation of research.
Thanks for all your help as we continue to move forward.
Dr Trevor Marshall wrote: So in many ways I am a pariah here - how dare I say I have a validated model for chronic disease! I have to seek out the folk who are still relatively untainted by the old-boys-club, such as the younger Nature editors here, and the post-Docs who will shape the next generation of research.
Well, maybe Trevor got through to some of those Nature editors with his poster on the differences in the VDR (and consequently inflammatory disease) between mice and men. Three papers published on-line in Nature Immunology on Aug. 5 highlight differennces between murine and human differentiation of Th-17 (T helper cells important in inflammation and innate immunity).
Not an earth shattering revelation for you, but Liu et al. demonstrate that antimicrobial activity is stimulated by 1,25 D in a human monocyte cell line infected with intracecllular M. tuberculosis. They identify cathelicidin as the responsible AMP by 'knock-down' of cathlecidin expression with microRNAs.
Being a teacher and administrator, this way of thinking does not suprise me. The students are taught to "get the right answer," not think for themselves nor think outside the box.
This in turn, has taught people to be reactive and not proactive. (No matter how much they would like to think they are.) It takes a completely new paradigm to REALLY think outside the box, to really be able to think about the abstract unimaginable, not just the visually concrete.
I hope that enough researchers in my generation will be open enough after going through standard education, will be open to think of different ways of thinking to make new discoveries like Leonardo Da Vinci.
____________________ Brenda, Writing in for my best friend with neurosarcoidosis.
I am not expecting radical change to occur within the current generation of physicians. Indeed, a significant proportion of them will be struck down by the same Th1 disease they cannot accept as communicable It will take another generation to effect radical change, IMO.