JoAnne S. Richards, Ph.D.
Department of Molecular and Cellular Biology
Ph.D.: Brown University, Providence
Postdoctoral training: University of Michigan, Ann Arbor
Ovarian Cell Differentiation, Ovulation and Cancer
The biological challenge to be met by the mammalian ovary is to maintain the continuous development of small follicles and, at the same time, to allow other follicles to ovulate and release a fertilizable egg. These dynamic events are orchestrated by many interwoven molecular, biochemical and hormonal signals. Ultimately less than 1 percent of the follicles in the ovary ovulate. Key regulators of ovarian follicle development and ovulation are follicle stimulating hormone (FSH) and luteinizing hormone (LH). My research interests focus on the molecular mechanisms by which these molecules regulate ovarian cell gene expression and alter cell function. Because each follicle is a developmental system unto itself, many of the genes regulated during this process are associated with ovarian cell fate decisions and involve specific signaling cascades including nuclear hormone receptors. Follicle growth also involves granulosa cell proliferation and differentiation; the latter being dependent on the induction of ovarian specific genes such as the LH receptor. Ovulation is a unique event during which the mature oocyte is released from the ovary and the follicular cells associated with this process acquire a vast new repertoire of expressed genes. Our recent novel observations indicate that cumulus cells surrounding the ovulated oocyte express specific immune cell-related genes. To understand the role of these ovarian specific genes, mutant mouse models, gene profiling and primary cell culture systems are being used. Our goal in the next decade is to understand how the ovary is formed, what endocrine signals and genes regulate follicular growth and follicular cell function and how ovulation occurs. Current research also focuses on several ovarian cancer models. A major issue facing women today is the detection and successful elimination of ovarian cancer. Mouse models for ovarian cell surface epithelial (OSE) cancer and granulosa cell tumors (GCT) are being developed to understand and cure these insidious diseases. Most specifically, we have generated a mouse model that mimics human ovarian serous adenocarcinomas. Using these mouse models we should be able to determine how steroids hormones impact ovarian cancer progression and metastases.
Baylor College of Medicine
One Baylor Plaza, DeBakey M525A
Houston, TX 77030
- Mullany LK, Richards JS (2012). Minireview: Animal models and mechanisms of ovarian cancer development. Endocrinology 153:1585-1592.
- Mullany LK, Liu Z, King ER, Wong KK, Richards JS (2012) Wild type tumor repressor protein 53 (TRP53) promotes ovarian cancer cell survival. Endocrinology 153:1638-1648.
- Fan HY, Liu Z, Johnson PF, Richards JS (2011) CCAAT/enhancer-binding proteins (C/EBP)- and – are essential for ovulation, luteinization and the expression of key target genes. Mol Endocrinol 25:253-268.
- Mullany LK, Fan HY, Liu Z, White LD, Marshall A, Creighton C, Richards JS (2011). Molecular and Functional Characteristics of Ovarian Surface Epithelial Cells Transformed by KrasG12D and loss of Pten in a Mouse Model in vivo. Oncogene 30: 3522-3536.
- Richards JS, Fan H-Y, Liu Z, Tsoi M, Lague MN, Boyer A, Boerboom D (2011). Either Kras activation or Pten loss similarly enhance the dominant-stable CTNNB1- induced genetic program to promote granulosa cell tumor development in ovary and testis. Oncogene 31:1504-1520.
- Liu Z, Fan HY, Wang Y, Richards JS. (2010). Targeted Disruption of Mapk14 (p38MAPKα) in Granulosa Cells and Cumulus Cells Causes Cell-Specific Changes in Gene Expression Profiles that Rescue Cumulus Cell-Oocyte Complex Expansion and Maintain Fertility. Mol Endocrinol 24:1794-1804.
- Fan HY, O'Connor A, Shitanaka M, Shimada M, Liu Z, Richards JS. (2010). β-Catenin (CTNNB1) Promotes Preovulatory Follicular Development but Represses LH-Mediated Ovulation and Luteinization. Mol Endocrinol 24: 1529-1542.
- Richards JS and Pangas SA. (2010). The ovary: basic biology and clinical implications. J Clin Invest 120:963-972.
- Fan HY and Richards JS. (2010). Physiological and pathological actions of RAS in the ovary. Mol Endocrinol 24:286-298 (A Minireview).
- Fan HY, Liu Z, Shimada M, Sterneck E, Johnson PF, Hedrick SM, Richards JS. (2009). MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science: 324:938-941.