"During the years following the discovery of the structure of DNA, we thought in terms of single genes, proteins, molecular pathways and diseases," said Hotamisligil. That was the first revolution in biological sciences. "Now, we are in the midst of a second revolution. We have the means to think collectively of genes, proteins and pathways as applicable to complex biological processes–an integrated approach to understanding larger systems in the whole organism and how these systems respond to environmental cues." At HSPH, he added, researchers want to capitalize on these capabilities and go a step further to see how the intersection of biology and environment plays out in the general human population.

HSPH is poised to take full advantage of the emerging opportunities in biological sciences with the establishment of the new Department of Genetics and Complex Diseases (GCD). The department will develop basic research initiatives that address the adaptations and responses of complex biological networks to environmental stresses. GCD will create programs that will combine molecular and cellular biology with genomics and proteomics, with the aim of preventing complex human diseases such as diabetes and cancer.

Hotamisligil, principal investigator of a lab in the Department of Nutrition that researches regulatory pathways in the body that control metabolism, will chair the new department.

"I am excited by the new department’s expected contributions to extending our epidemiologic knowledge about risks for complex diseases such as cancer, heart disease and diabetes and to an understanding of disease mechanisms," said HSPH Dean Barry Bloom. "We also anticipate valuable synergies for researchers across different fields and departments."

The core faculty in the new department is drawn from the former Department of Cancer Cell Biology as well as from the Department of Nutrition. In addition to Hotamisligil, the primary faculty members in the Department of Genetics and Complex Diseases are Bruce Demple, Karl Kelsey, Guy Reed, Marianne Wessling-Resnick, Dieter Wolf and Zhi-Min Yuan.

"The new Department of Genetics and Complex Diseases creates an important opportunity to bring together our strengths in cancer cell biology with our emerging capacity for investigating the determinants of metabolic diseases," said James Ware, Dean for Academic Affairs. "We are enthusiastic about the work of our core faculty, and we look forward to expanding the department through planned recruitment."

The new department is currently seeking candidates for several junior faculty positions.

Following the acceptance and application of Mendelian genetics in the 20th century, researchers focused on identifying single genes implicated in some diseases. Inheritable mutations responsible for sickle cell anemia, cystic fibrosis, hemophilia and some forms of deafness–to name a few–were identified. The relationship between the mutations and ensuing medical conditions was fairly straightforward, and geneticists could predict with some certainty if someone were at risk for these kinds of inherited problems.

But many medical conditions are not so easily ferreted out. In addition to genetics, other factors such as the environment, behavior and nutrition may intersect with one another in a single disease or cluster of diseases, making approaches to understanding these conditions more complicated.

"This is our core vision: to better understand the complex systems and biological responses that are controlled by multiple genes and factors," said Hotamisligil. "Our biological identities can be defined as a combination of our genetic material and the integrated responses to external stimuli such as stress, toxins, radiation and nutrients. The responses evoked by these factors contribute in substantial proportions to at least three-quarters of non-infectious health problems, and this is the area in which we will concentrate our efforts."

The new department will focus on several broad categories of health problems. Metabolic diseases, such as diabetes and obesity, and related cardiovascular disease will be studied. Once the bane largely of only the developed world, these diseases are now becoming increasingly present in developing countries. Hotamisligil estimates that if current trends continue, one out of every two adults and children will be suffering from some form of one of these diseases within the next 25 years.

Cancer is another broad category of interest to GCD researchers, who plan to investigate how stresses damage genetic material and how that damage leads to outcomes such as cancer.

In addition, Hotamisligil intends to support research into biological processes related to DNA damage and aging, addressing the internal causes of genetic wear and tear on systems as the body gets older.

Hotamisligil has already been in touch with faculty members in other departments at HSPH to identify cross-disciplinary research prospects.

"We need a multidisciplinary approach to some of the most important public health problems of our time," said Hotamisligil. "We have a tremendous advantage by being at a school with unique components of the interdisciplinary platform needed and within a city where there are so many layers of opportunities for joint research efforts. In pursuing these health problems, we want to go beyond the traditional borders of each discipline in basic molecular, genetic and population sciences and create the intellectual environment for the scientists in these disciplines to naturally converge their interests."

For more information, contact Hotamisligil at ghotamis@hsph.harvard.edu.