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:
- Fertility preservation in cancer patients: Cancer and cancer chemotherapy lead to premature ovarian failure and sterility as a result of direct damage to the ovary or as a result of hypothalamic/pituitary insufficiency. Premature ovarian insufficiency causes failure to achieve spontaneous normal puberty and optimal growth potential in girls, and lead to sexual dysfunction, infertility, and poor pregnancy outcomes in women. We are building interdisciplinary clinical research within the institution to enhance reproductive health and fertility preservation in cancer patients. In addition, my 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. The long-term goal of my research is to identify drug therapy to prevent ovarian toxicity and assist in preserving fertility and reproductive health in female cancer patients. The objectives of my research are focused on identifying the molecular signaling pathways that result in chemotherapy-induced primordial follicle depletion, and selectively intercepting these signaling pathways at various levels and as early as possible to prevent DNA damage and ovarian toxicity in cancer patients. A novel approach to preserve fertility and reproductive health in cancer survivors is to selectively enhance the resistance of normal ovarian tissues to chemotherapy-induced toxicity by enhancing the ovary’s own defense mechanisms against chemotherapy. Enhancing chemotherapy defense in the ovary could be performed at various steps of chemotherapy metabolism. Chemotherapy metabolism involves drug accumulation trafficking and transactivation, nuclear translocation, DNA binding, and induction of cell death and apoptosis. These steps are executed by defined signaling pathways that include drug metabolizing enzymes (DMEs), proteasome transporters, DNA repair genes, apoptosis, and cell cycle machinery. My lab is investigating the utilization of these signaling pathways in protecting the ovary from chemotherapy toxicity. 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.
- Germ cell differentiation and oocyte development: This research aims at identifying factors that regulate gametogenesis, folliculogenesis, oocyte development and maturation, and early embryonic development in humans. My lab in collaboration with other investigators is working on utilizing 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 and cow 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.
- Composite images from spectral confocal microscopy collecting images every 10 nm from 575-700 nm, span the emission profile of DXR (graph). Representative images from 4 and 48 hours post-DXR injection reveal different subcellular accumulation patterns of the drug in stroma and granulosa cells. DXR becomes concentrated in perinuclear structures only in the granulosa cells.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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
- Will Klein
- Samet Albayrak
- Sarah Horak