Problems in the Biology of Complex Diseases

Weekly Colloquium - Friday, 9-11 am, Keating/Bio5 103

Complex diseases (CDs: e.g., asthma, allergy, COPD, obesity, inflammatory bowel disease, hypertension, coronary artery disease, diabetes, rheumatoid arthritis, multiple sclerosis, schizophrenia) are the next major challenge in human biology because they are at the same time unique, common and difficult to decipher. The complexity of CDs lies in their pathogenesis, in which a constellation of environmental and genetic factors interact in intricate ways to alter biological thresholds and response patterns, modifying disease susceptibility. Since both genes and environmental exposures contribute to CDs, the biological pathways involved in CD pathogenesis depend on the genetic background of a given population and the specific environment to which that population is exposed. Hence, asthma, obesity and hypertension in Arizona may not be the same as asthma, obesity and hypertension in Iceland.

Currently, much active effort is directed toward identifying genes involved in CDs by genome-wide association (GWA) studies. This effort, which relies on recent technologies and large reference databases, is rapidly producing a prodigious amount of information. Interestingly, far from providing definitive answers, GWA studies seem to be generating more and more questions – we have more candidate genes, but we still do not know how they contribute to disease and how they interact with one another and with the environment.

Thus, it is precisely the progress of CD genetics that is creating an acute need for a novel CD biology. While the list of candidate genes for CDs gets longer, knowledge about the biological mechanisms through which genetic and environmental factors interact and ultimately impact on CD pathogenesis lags behind. Yet, unless we understand the mechanisms underlying CDs, we will not understand the diseases themselves and we will not be able to develop effective preventive and therapeutic measures.

Making sense of the complexity of CDs is not within reach of individual disciplines. Rather, it requires a concerted, interdisciplinary effort involving experts in environmental studies, immunological and clinical phenotyping, genetic epidemiology, population genetics, epigenetics, functional genomics of human and animal models. This Colloquium reflects the UofA’s growing interest in CDs. Its goal is to provide a platform that will catalyze discussions among experts from the University and elsewhere in the country, thereby fostering the emergence of a new experimental and conceptual paradigm in CD biology.

Program/Topics (Invited Speakers) have included:

  • What is a complex disease? (D. Vercelli) 
  • Epidemiology & Phenotypes (F. Martinez) 
  • Epidemiology & Phenotypes (M. Halonen) 
  • Genetic components (W. Klimecki) 
  • Ancestry/population movements/natural selection (M. Hammer) 
  • Gene- environment interactions (F. Martinez) 
  • Genome-wide association studies (C. Ober, U. Chicago)
  • Cancer Epigenetics/mechanisms (B. Futscher and/or C. Smith)
  • Transgenerational epigenetic effects (M. Skinner, Washington State)
  • Model systems (non-humans) (V. Chandler)
  • Microbial exposures & their developmental impact (D. Kasper, Harvard)