This Mentored Patient-Oriented Research Career Development Award (K23) will provide a promising early- stage investigator, Dr. Knudtson, with the knowledge and skills requisite to become an independent clinical- investigator in the field of endometriosis. Dr. Knudtson's interest is in applying novel, basic science findings into translational clinical research on the effects of the hyaluronic acid (HA) pathway, estrogen and progesterone in the development of the endometriotic lesion. Dr. Knudtson will actively participate in a variety of training activities in the learning of clinical investigation for prospective non-interventional studies and understanding of clinical trials including study design through statistical analysis. She will apply her knowledge and skills learned to the execution of an innovative research project on development of endometriosis from menstrual endometrium and the roles of HA/CD44, estrogen and progesterone. The training activities address gaps in Dr. Knudtson's knowledge and skills, and the research project addresses a significant gap in understanding of endometriosis. Endometriosis develops from menstrual endometrium and is a cause of pain and infertility. Differences exist in menstrual endometrium from women with and without endometriosis.
The specific aims of this proposed study are: (1) To determine the effect of oral contraceptive pills (OCPs) on the HA enzymes in women with endometriosis compared to women without endometriosis; (2) To establish the role of the CD44 variants, the primary receptor for HA, in menstrual endometrium versus the endometriosis lesion. These studies will pursue prospective, non-interventional trials and incorporate translational and clinical research. The training aims consist of: (1) developing expertise in prospective clinical studies using human tissues; (2) obtaining structured clinical research training through a Masters of Science in Clinical Investigation-Translational Science. Dr. Knudtson's primary mentor is Dr. Robert Schenken, a physician scientist, with a world renowned expertise in endometriosis. Her co-mentor is Dr. Randal Robinson, a physician scientist with expertise in clinical studies. The advising committee consists of Dr. Rajeshwar Tekmal (translational researcher), Dr. Joel Tsevat (physician scientist with previous K scholars), and Dr. Jonathan Gelfond (biostatistician). Dr. Knudtson's unique strengths include aptitude and experience in translational research, with clinical knowledge and desire to become a clinical investigator. The combined expertise and experience represented by the mentors and advising committee will enable her to achieve the career goals proposed and to become an independent physician scientist focused on patient oriented research in endometriosis.
( 3 sentences) Understanding the development of endometriosis from menstrual endometrium is key to improve treatment for women with endometriosis. These studies described will evaluate the novel concept that hyaluronic acid is involved in the development of the early endometriotic lesion, from endometrium to endometriosis, and that its action is exacerbated by estrogen and progesterone.
