Wednesday, October 16, 2013

Personalization of Medicine and the Science of Scale: A Summary of the 8th Annual ITMAT Symposium

Yesterday was the second and last day of the Institute for Translational Medicine & Therapeutics (ITMAT) 8th Annual International Symposium here at the University of Pennsylvania.  ITMAT is a group that promotes translational research and medical applications around some of the Philadelphia medical campuses.  What is especially cool about this symposium is that it is always an international symposium which features participants from many institutions from all around the world.  The theme of this year's symposium was "Harnessing the Paradox: Personalization and the Science of Scale" and it was all about using huge data sets and high-throughput techniques to improve patient care and our general understanding of medicine.  The three general themes of the meeting that I attended were the general biomedical research landscape, microbiomics, and metabolomics/metabolism (with a focus on cancer).  The fourth, which I missed, was about emerging technologies and concepts in translation.

This symposium really was awesome so I am excited to go back through my notes and outline some of the highlights during the talks.  Now all of the talks were really interesting and in depth, and each topic would warrant its own separate blog post.  To keep things relatively brief and digestible, I am going to point out some very general highlights from each talk, as well as provide some links and literature for further reading so that you can check out the topics and speakers that interest you.  If you would like to watch videos of the talks yourself, they should be available on the ITMAT website for general viewing in the near future, and I would definitely encourage you to check them out.  I'll update the blog with a link to the videos when I see they are up.  Finally, I was unfortunately not able to attend all of the talks because I had to run to lab throughout the symposium, so here I am only going to mention the talks I attended.  Go here for a complete agenda and check out reference [1] for a formal review of the organization by its leader.

The Biomedical Research Landscape

The first section was titled 'the biomedical research landscape' and set the stage for the following sections by going into the value of general translational medicine and some ways people are actively promoting its value throughout the world.  Leroy Hood, MD, PhD kicked off the talks by going over systems medicine (the application of systems biology approaches to disease) and his idea for P4 medicine (P4 stands for predictive, preventative, personalized, and participatory).  Dr Hood talked about the increasing importance of using large data sets in medicine (large data sets referring to large prospective studies like the UK Biobank described below).  He also stressed the importance of personalized medicine as we move forward in translational research, and the importance of increasing n=1 studies which, while they do not focus on statistical trends and general patterns, provide interesting observations that will likely lead to valuable research in the future.

Kicking off this year's symposium in Philadelphia.
I had to take care of some things in lab after the first talk, but the next talk I saw (although I got in part way through) was given by the Chief Medical Officer and Chief Medical Advisor to the UK government Sally Davies MB, ChB.  She gave a great overview of the research being funded by the UK NHS and stressed how much effort they are putting into promoting collaboration through their granting and leadership efforts, especially collaborations between academia and industry.  She also pointed out some financial research which outlined the returns on government investments in research, which I agree is important to provide to justify the investments of the government in medical research.

The last lecture of this section was given by Sir Rory Colins about the UK Biobank.  The main point of this talk was to promote the use of the UK Biobank among researchers.  He really stressed the point that they built the data base and want researchers to use it (and the intellectual property lies with the researchers so your findings are yours).  The UK Biobank has enrolled, and collected numerous medical test results from, 500 thousand subjects throughout the UK.  This is actually a really cool resource and I'm surprised more research has not been done using it.  This is uniquely important because it is providing a huge data resource that researchers could use with minimal investment, and could be especially useful in education by allowing students to work with real data sets.

The Microbiome

The next section of the symposium was all about the microbiome, which was a section I was particularly interested in because I do microbiome research here at Penn.  Martin Blaser, MD kicked off this section's talks by first giving us an introduction to the microbiome.  He explained that there are ten times more microbial cells in the body than human cells, and while the human genome contains about 23 thousand genes, there are about 20 million microbial genes within the human associated microbe colonies (which is actually a higher number than I have previously heard estimated).  Because the microbial communities of humans are so numerous and diverse, they are important to understand.  These studies used to be performed using culture based techniques, but are now done using culture independent techniques with high-throughput sequencing technologies.  Dr Blaser talked about the use of antibiotics and how they perturb the gut microbiome, especially in the context of development early in life.  Check out reference [2] for a review, written by Dr Blaser, about the microbiome associated with health and disease.

The next talk was given by Rick Bushman, PhD who is a professor here at Penn.  He talked about the human gut virome (the communities of viruses that colonize the gut) and especially focused on the gut.  He talked about hypervariable regions found within phage genomes and what they tell us about phage evolution/adaptation.  The gut viruses are also very diverse, with each community looking completely unique and nothing like any other collected communities or any communities previously described.

In a shift from Dr Blaser's talk which focused on the early gut microbiomes, Paul O'Toole, PhD discussed the elderly gut microbiome and how it interacts with diet and health.  He showed that young adult gut microbiomes are significantly different from elderly microbiomes, and also that the diversity of the microbiome (how many different kinds of bacterial species present in the community) are correlated with the diversity of food intake (how many different kinds of food are eaten).  He also touched on the importance of looking at Archaea, which have so far been ignored compared to the study of bacteria.

The classic catalog system at the College of Physicians in
downtown Philly (the reception/dinner location).
Josbert Keller, MD, PhD discussed the use of fecal transplants to treat Clostridium difficile (C. diff) infections [3].  These infections occur in patients who have had their gut bacterial communities wiped out by heavy antibiotics and, in the absence of commensal bacteria, C. diff is able to grow without its normal competition which brings it to a diseased state.  One treatment that has been gaining a lot of attention, and seems to be effective, is fecal transplantation.  By providing the infected gut with commensal bacteria that are able to colonize the gut, the C. diff is no longer able to grow without competition and so the infectious disease is effectively treated.  Because this is a complicated procedure and not standardized (because it involves donors), the field will probably move toward probiotic pills that provide the exact bacteria needed for colonization.

The microbiome section, as well as the day, concluded with a talk given by Jayne Danska, PhD.  Dr Danska talked about the interactions between the gut microbiome, sex, and autoimmune disease.  I thought this was particularly cool because I had never read much about the research outlining these interactions.  Studies have shown that females are at higher risk for autoimmune disease development, and this is true for humans and mice.  Interestingly, when female mouse guts were colonized with male gut microbiota through a fecal transplant, the risks of the females were greatly reduced to rates near the males.  She also found that microbiome alterations can alter levels of testosterone, which suggests links between sex hormone levels and the bacteria that colonize humans.  This is all really cool, and it makes me wonder what effects antibiotics may have on sex hormone levels or autoimmune disease risks.  This research may also lead to cool new potential microbiome based treatments for autoimmune diseases, and it will be a cool research program to follow in future literature.

Metabolomics & Metabolism

The morning of the second day was all about metabolomics and metabolism.  The first talk was given by Joshua Rabinowitz, MD, PhD, and he focused on an understanding of metabolism that has relevance in cancer treatment.  Dr Rabinowitz focused on basic understanding of cancer related metabolic processes, and specifically NADPH.  He found that in many cases, cancer cells, which often have abundances of metabolites, are barely producing enough NADPH for normal functioning.  This is important because it provides us with a target (NADPH) for cancer therapy, such as inhibition of its synthesis.  The following metabolic talks were given by Benjamin Tu, PhDSir Stephen O’Rahilly, MD, and Chi Van Dang, MD, PhD.  There is a lot of interesting and promising research going on with cancer and other disease metabolism (such as obesity and related metabolic diseases) and it will be cool to see how these progress in the future.


Overall this was a really cool symposium.  I thought the theme of stressing the importance of integrating high-throughput technologies and large data sets into medical research was both interesting and important.  It will be particularly important for governments to invest in large data collecting programs like the UK Biobank because these will provide easily accessible resources for large scale research that may be relevant to hundreds of thousands of citizens, and could also be used to promote research education by allowing students to deal with actual data that has not yet been fully analyzed.  I am obviously biased since this is the work I do, but it is becoming increasingly apparent that an understanding of the microbiome is crucial for a complete medical understanding.  Additionally, while the focus of this symposium was on the human gut microbiome, microbial communities on other body sites also play important roles in health, including the mouth, respiratory tract, and skin.  Finally these high-throughput approaches will be valuable in metabolic research, especially that research related to cancer and metabolic diseases like obesity.  Understanding how to use high-throughput techniques, and how to best utilize these in translational research will be a crucial part of progressing our general understanding of medicine, as well as improving the care of patients.

Do you want more info on a particular topic, did I get something wrong, do you think this symposium is really cool, or are you itching to comment?  Leave a comment below because I would love to hear from you.

Works Cited

1.  Fitzgerald GA (2013). Anecdotes from ITMAT: Building Capacity for Translational Science Clin Pharmacol Ther DOI: 10.1038/clpt.2013.84

2.  Cho I, Blaser MJ (2012). The human microbiome: at the interface of health and disease Nat Rev Genet DOI: 10.1038/nrg3182

3.  Els van Nood, M.D., Anne Vrieze, M.D., Max Nieuwdorp, M.D., Ph.D., Susana Fuentes, Ph.D., Erwin G. Zoetendal, Ph.D., Willem M. de Vos, Ph.D., Caroline E. Visser, M.D., Ph.D., Ed J. Kuijper, M.D., Ph.D., Joep F.W.M. Bartelsman, M.D., Jan G.P. Tijssen, Ph.D (2013). Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile N Engl J Med DOI: 10.1056/NEJMoa1205037

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