Felicia V. Nowak, M.D.,Ph.D.

     The organization and ultimate normal function of the adult mammalian brain reflects the orchestration of extensive cellular migration, selective survival and differentiation during development.  Many neuronal cells have the potential to display a seemingly endless array of phenotypes and thus retain a degree of functional plasticity throughout life.  Understanding the roles of individual gene products, including neuropeptides, in this process will enhance our understanding of normal brain development and our capacity to manipulate brain function in disease states.

     My laboratory is focused on studying the functions and mechanisms of action of two neuropeptide genes, the preoptic regulatory factors, PORF-1 and PORF-2.  These genes give rise to two unique peptides which are expressed in the mammalian brain and whose expression is regulated by age, gender and hormonal status in a brain region dependent manner.  Areas of special interest include the hypothalamus, a major regulatory region for neuroendocrine and metabolic functions and the hippocampus, a key area in learning and memory.  PORF-1 and PORF-2 may be involved in gender specific development and function of these brain regions.

     Current work in the laboratory is concentrated in three specific areas of inquiry. First, what are the 5' promoter and regulatory regions in the porf-1 and porf-2 genes responsible for the observed hormonal effects on region dependent expression? Second, what are the effects of overexpression of PORF-1 and PORF-2 on growth and survival of cultured non neural and neural cells, including undifferentiated neuronal precursor cells, and what are the subcellular locations of the expressed peptides? Third, what are the phenotypic effects of knocking out expression of the porf-1 and porf-2 genes in vivo and in vitro?

Selected References:

• Nowak, F.V. Torres, G.O., and Hu, S.-B. 1999 Differential gene expression response to gonadal hormones by preoptic regulatory factors 1 and 2 in the female rat brain. Neuroendocrinology 69:191-201.

• Nowak, F.V. and Gore, A.C. 1999 Perinatal developmental changes in expression of the neuropeptide genes preoptic regulatory factor-1 and ­2, neuropeptide Y and GnRH in rat hypothalamus. Journal of Neuroendocrinology 11:951-958.

• Nowak, F.V.  1997   Modulation of preoptic regulatory factor 2 (porf-2) messenger RNAs by castration and hypophysectomy. Endocrine, 6:57-64.

• Hu, S.-B. and Nowak, F.V.  1995 Sex-specific changes in preoptic regulatory factor-1 and preoptic regulatory factor-2 mRNA expression in the rat brain during development.   Endocrine, 3:421-424.

• Hu, S.-B. and Nowak, F.V. 1994  Regional distinction in age-related changes of preoptic regulatory factor-1 and preoptic regulatory factor-2 mRNA expression in the rat brain.   Molecular and Cellular Neurosciences, 5:376-381.