Dr. Sana Salih's Laboratory

Molecular Determinants of Oocyte Development, Fertilization, and Early Embryogenesis in Humans.

Research overview: Research in my laboratory seeks to identify novel mechanisms to improve fertility and reproductive health outcomes in women. In particular, we are investigating the molecular mechanisms and signaling pathways that are involved in oogenesis, folliculogenesis, fertilization, and early embryonic development in humans. Advanced age, genetic factors, environmental toxins, and exposure to chemo- and radiations therapy lead to perturbed follicular developments. This translates into poor oocyte quality and interferes with the orderly and intricate process of oocyte maturation, ovulation, fertilization, implantation, and early embryonic development, thus culminating in poor reproductive health outcomes. This is particularly relevant to girls and women that are diagnosed with cancer.

We are currently looking at the following aspects of human reproduction:

1. Germ cell differentiation and development: Identifying factors that regulate gametogenesis, folliculogenesis, oocyte development and maturation, and early embryonic development in humans. We utilize computer bioinformatics and sequence alignment tools to identify structural, functional, and evolutionary conserved homologous genes that are essential in reproduction in other model organisms such as the fly, the worm, and nonhuman primates. We hypothesize that evolutionary conserved genes will have similar function in human reproduction. We use the mouse model as well as human tissues to further study candidate genes with infertility and reproductive failure traits and phenotypes in order to ascertain their role in reproduction. In addition, we are investigating the feasibility of utilizing stem cell-derived germ cell and gametes as a model system to further elucidate key factors that are essential for gametogenesis and for cell therapy.
   
   
2. Fertility preservation in cancer patients: Our lab is working on identifying the multidrug resistant (MDR) phenotype and signaling pathways that could lead to molecular shielding of the ovary from chemotherapy and radiation therapy. We are also building interdisciplinary clinical research within the institution to enhance reproductive health and fertility preservation in cancer patients. Cancer and cancer therapeutics lead to premature gonadal failure and sterility, hypothalamic/pituitary insufficiency, failure to achieve spontaneous and normal puberty and optimal growth potential in children, sexual dysfunction, infertility, and poor pregnancy outcomes with increase spontaneous abortion, preterm labor, and delivery of low birth weight infants. The ultimate goal of this project will be to identify therapies that could assist cancer patients achieve genetically related healthy offspring as naturally as possible.
   
   
3. Role of estrogen metabolites and estrogen metabolizing enzymes in human reproduction and endometrial carcinogenesis.

Selected References:

1. Ofili EO, Mayberry R, Alema-Mensah E, Saleem S, Hamirani K, Jones C, Salih S, Lankford B, Oduwole A, Igho-Pemu P.. Gender differences and practice implications of risk factors for frequent hospitalization for heart failure for urban center serving predominantly African-American patients. American Journal of Cardiology. 1999;83(9):1350 5.
   
   
2. Salih S, H Taylor. HOXA10 gene expression in human fallopian tube and ectopic pregnancy. American Journal of Obstetrics and Gynecology. 2004;190(5):1404-6.
   
   
3. Klien Klein RD, Salih S, Bessoni J, Bale AE. Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic laboratory. Genetics in Medicine. 2005;7(2):131-8.
   
   
4. Salih SM, Salama SA, Fadl AA, Nagamani M, Al-Hendy A. Expression and cyclic variations of catechol-O-methyl transferase in human endometrial stroma. Fertil Steril. 2007;4.
   
   
5. Salih SM, Jamaluddin M, Salama SA, Fadl AA, Nagamani M, Al-Hendy A. Regulation of catechol-O-methyltransferase expression in granulosa cells: a potential role for follicular arrest in polycystic ovary syndrome. Fertil Steril. 2007;3.
   
   
6. Salih S, Xu X, Veenstra TD, Duleba AJ, Fouad H, Nagamani M, Al-Hendy A. Lower levels of urinary 2-hydroxyestrogens in polycystic ovary syndrome. J Clin Endocrinol Metab. 2007.
   
   
7. Salih S, Salama S, Jamaluddin M, Fadl A, Blok L, Burger C, Nagamani M, Al-Hendy A. Progesterone-mediated regulation of Catechol-O-Methyl Transferase expression in endometrial cancer. Reprod Sci. 2007.
   
   
8. Salama A, Kamel M; Concepcion A; Xu X; Veenstra T; Salih S; Blotting S; and Kumar R. Effect of TNF-? on estrogen metabolism and endometrial cells: potential physiological and pathological relevance. Accepted for J Clin Endocrinol Metab (October, 2008).