The overall interest of Dr. Haddad's laboratory is the effect of low oxygen or hypoxia on cell function and development. Mammalian tissues are extremely sensitive to the stress of hypoxia and can only survive for relatively short periods of time. The Haddad lab is interested in the molecular mechanisms that underlie susceptibility to injury under these conditions, especially in nerve cells and glia. To examine the susceptibility of sensitive tissues to low oxygen, mice are studied with the use of electrophysiological, molecular biological and genetic techniques.
A strong component of Dr. Haddad's research is the use of an invertebrate model, the fruit fly Drosophila melanogaster. Researchers in the Haddad lab have discovered that the fruit fly is very tolerant to low oxygen conditions and we are therefore taking advantage of such well studied organism to investigate its genetic endowment to better understand how fruit flies survive extreme oxygen conditions. Using a variety of screens and mutational analysis, the Haddad lab has been able to dissect the genetic basis of tolerance of fruit flies to low oxygen. In addition, they have recently generated a D. melanogaster strain that lives perpetually in an extremely low-oxygen environment (4% O2, an oxygen level that is equivalent to about 4,000 m above Mt. Everest) through laboratory selection pressure using a continuing reduction of O2 over many generations. This phenotype is genetically stable as extreme hypoxia tolerance is an inherited trait in these hypoxia-selected flies. Gene expression profiling showed striking differences between tolerant and naïve flies, in larvae and adults, both quantitatively and qualitatively.
Presently, the Haddad lab is dissecting the role of a number of genes and genetic pathways in hypoxia tolerance in Drosophila melanogaster.