Applications for Training Program Now Being Accepted
Erin Johnson at a fume hood
The Interdisciplinary Training Program in Genetics and Complex Diseases supports "HSPH Roadmap Fellows" who are pursuing a range of interests, including "data mining," genetic disease susceptibility, software development for genome analysis, and the role of fat tissue in tumor susceptibility and cancer risk. The program is seeking more applicants.
IRONING OUT TB
Roadmap fellow Erin Johnson is working on a project resulting from a collaboration between Megan Murray, assistant professor of epidemiology, and Marianne Wessling-Resnick, professor of nutritional biochemistry.
A trained physician, Murray is overseeing a number of tuberculosis studies, including what makes someone susceptible to the disease. Caused by the M. tuberculosis pathogen, tuberculosis kills more than two million people each year and is a major worry for public health officials because the pathogen has become increasingly resistant to once-successful drug treatments. Murray's work led her to question the role of iron in the disease, and she reached out to Wessling-Resnick, who studies how the element is regulated in the body.
M. tuberculosis needs iron to grow and, as a result, is no friend of a protein called ferroportin, which ferries iron from cells and out of reach of the bacteria. However, ferroportin itself can be thwarted by a peptide called hepcidin, which binds to the protein and degrades it, leaving iron in cells at the mercy of the pathogen.
Johnson is working to understand how hepcidin-ferroportin interactions influence the growth of mycobacteria. She consults with Murray and Wessling-Resnick and attends both lab's group meetings, examining the subject from bench science and epidemiological points of view.
"This kind of collaboration between epidemiologists and bench scientists is brand new to me, and I find it highly motivational," said Johnson. "When you are in the lab, you are focused on the experiment in front of you, but when you hear how this work could one day affect populations, it closes the distance between the bench and people's day-to-day lives."
Looking for Roadmap Fellows
Apply for the next round of HSPH Roadmap Fellowships. For more information, visit http://www.hsph.harvard.edu/roadmap/eligibility.html or contact Julie Gound at 617-432-0054 or at jgound@hsph.harvard.edu.JNK GENES
Doctoral student Sara Vallerie is exploring the role of JNK genes in metabolic syndrome-a cluster of metabolic disorders such as diabetes, obesity, and heart disease. More than 50 million Americans have metabolic syndrome, according to the American Heart Association.
Studies led by Gökhan Hotamisligil, James Stevens Simmons Professor of Genetics and Metabolism, have demonstrated an important role for inflammation in obesity, diabetes, and associated diseases. In 2002, a team of researchers led by Hotamisligil identified an form of the gene JNK as a key component of this inflammatory pathway, interfering with insulin sensitivity in the course of obesity, obesity-induced insulin resistance, and type 2 diabetes. To test this observation, the team bred mice that lacked JNK1 genes and then demonstrated the animals' resistance to gaining weight and becoming diabetic-even when put on high-fat diets.
One hypothesis that emerged during the course of this work was that macrophages may play a role. Vallerie is now examining this idea, testing to see if macrophages interfere with insulin in fat tissue or elsewhere. She is also working on a second project involving how a form of JNK3 predominantly present in the brain may be involved with the central control of both inflammation and glucose homeostasis. Her work at HSPH has garnered her a new, four-year grant from the NIH to continue research in this area.
In addition to these training opportunities, the Roadmap Fellowship also has provided Vallerie with the opportunity to use an array of genomic and bioinformatics tools.
HEARTY GENES
Edward Ruiz-Narváez
Ruiz-Narváez's work was published last month in the Journal of Lipid Research, showing that variants of the APOC3-but not APOA5-gene were associated with an increased risk of heart attack among Costa Ricans. Now, he is working with Peter Kraft, assistant professor of epidemiology, to run statistical analyses of lifestyle questionnaires from study participants to see if their diets interplay with the gene to increase heart attack risk.
The fellowship has also given Ruiz-Narváez the opportunity to explore a different scientific question. A reigning hypothesis in the field of diabetes research is that people are predisposed to the disease because natural selection has favored so-called "thrifty" genes that store fat, allowing humans to survive in times of deprivation. While this has been a popular hypothesis, evidence of the action of natural selection on putative "thrifty" genes is scarce, according to Ruiz-Narváez.
The PPARG gene is a key regulator of energy homeostasis and a candidate to test the thrifty gene hypothesis. In an article published last year in the Journal of Medical Genetics, Ruiz-Narváez tested the hypothesis that a variant in the PPARG gene that protects against diabetes has been subjected to negative selection during human evolution. By analyzing published data and using two different statistical approaches, Ruiz-Narváez pegged the approximate age of this gene allele-showing that natural selection does not appear to have preferred one more than the other during human evolution, at least for this particular example. In the same published paper, Ruiz-Narváez proposed a supposition of his own to refine the original "thrifty" gene hypothesis.
"The Roadmap Fellowship has allowed me to see my research from several scientific viewpoints and to interact with researchers I may have otherwise not met," said Ruiz-Narváez.
Copyright, 2009, President and Fellows of Harvard College
