2007: William F. Crowley, MD
Director of Clinical Research – Massachusuetts General Hospital
|William F. Crowley, MD
Professor of Medicine
Director of Reproductive Endocrine Sciences – Harvard Medical School
Chief of Reproductive Endocrine Unit – Department of Medicine
Director of Clinical Research – Massachusuetts General Hospital
Dr. Crowley is Professor of Medicine at Harvard Medical School, the Chief of the Reproductive Endocrine Unit of the Department of Medicine at Massachusetts General Hospital, and the Director of the Harvard-wide Reproductive Endocrine Sciences Center at Harvard Medical School.
In addition, he serves as the Director of Clinical Research for the Massachusuetts General Hospital, and is a member of the MGH General Executive Committee, Executive Committee on Research, and Chiefs Council. In these roles he has been working to focus the MGH’s efforts on clinical research, to provide infrastructure for translational research, and to build an infrastructure for both clinical trials and outcomes/epidemiology/disease management research.
Dr. Crowley’s laboratory has a remarkable track record of training pre- and post-doctoral fellows (48 as of 2003) for independent careers in academic medicine and biomedical research. Over 80% of these previous trainees remain in academic settings, nine are full Professors, two are Associate Professors, and 68% are women.
In recognition of his training record, Dr. Crowley was awarded the Mentor of the Year by Women in Endocrinology in the year 2000, the first time this award was given to a man. He will also be the recipient of the Endocrine Society’s top scientific award, the Fred Conrad Koch Award, at the June 2005 meeting in San Diego.
The overall goal of his laboratory over the past 25 years has been to improve the understanding and treatment of reproductive disorders affecting humans. We have focused on gaining insights into the neuroendocrine and genetic control of GnRH secretion, its impact upon gonadotropin secretion and gonadal physiology as well as it regulation by higher neural regulation. To accomplish these tasks, we use a wide spectrum of techniques and complementary approaches. These include using normal and disease models in the human; information from the Human Genome Project; and biochemical, cellular, genetic and animal approaches wherever appropriate.
Significant Contributions of The Laboratory
• Documentation of the ability of GnRH agonist to induce desensitization of pituitary gonadotropin secretion in the human (Crowley WF, et al, NEJM 1980;302:1052-57; Crowley WF, et al, LHRH in Hypogonadotropic Hypogonadism, PARFR Series on Fertility Recognition, Harper & Row 1981;321-33.
• The initial description of GnRH agonists for therapeutic effect in a human disease model (central precocious puberty) (Crowley WF, et al, JCEM 1981;52:370-72; Comite F, et al, NEJM 1981;305:1546-50).
• The first use of GnRH agonist-induced castration to examine the impact of sex steroids on the GH-IGF and skeletal axis (Mansfield MJ, et al, NEJM 1983;309:1286-90).
• The first documentation of the normal timing, onset, and progression of adrenarche in a longitudinal study of children with central precocious puberty during GnRHa therapy; (Wierman ME, et al, JCI 1986;77:121-26; Palmert MR, JCEM 2001;86(9):4536-42).
• The initial description of gonadotropin-independent sexual precocity and its cyclicity during GnRH agonist therapy of sexual precocity (Wierman MR, et al, NEJM 1985;312:65-72).
• The first FDA approval for use of GnRH agonists as a therapy for a human condition (central precocious puberty), for which it still remains the therapy of choice for this condition throughout the world (1988).
• The initial follow-up of a cohort of 140 children with CPP for 16 years and first report on their final heights, reproductive status, and body compositions (Jay N, et al, JCEM 1992;75:890-94; Palmert MR, JCEM 1999;84:4480-97).
• The initial description of induction of an LH surge, ovulation, and normal corpus luteum function with pulsatile GnRH administration in women with hypothalamic amenorrhea (Crowley WF, et al, JCEM 1980;51:173-75).
• The first FDA approval for the use of pulsatile GnRH for use in ovulation induction in Kallman’s Syndrome.
• The initial description of pulsatile progesterone secretion and progressive slowing of the GnRH pulse generator during the luteal phase in the human (Filicori M, et al, JCI 1984;72:1638-47).
• The accurate characterization of the frequency of GnRH secretion across the human menstrual cycle (Filicori M, et al, JCEM 1986;62:1136-44).
• The documentation of an abnormally high and sustained frequency of GnRH secretion in PCOD (Waldstreicher J, JCEM 1988;66:165-72).
• The first definition of the full spectrum of abnormalities of endogenous secretion causing hypothalamic amenorrhea.
• The documentation of >90% efficacy for a physiologically based frequency program and varying doses of GnRH in ovulation induction in women with eu- and hypogonadotropism (Santoro N, et al, Endo Review 1986;7:11-23; Santoro N, et al, JCEM 1986;62:109-16).
• The initial description of the economic impact of multiple gestations during IVF (Callahan TL, NEJM 1994;331:244-49).
• The ability to decrease GnRH secretion during the midcycle LH surge (Hall JE, et al, PNAS 1994;91:6894-98; Lavoie HB, et al, Neuroendocrinology 1998;76:363-69).
• The initial use of pulsatile GnRH therapy in women with hypogonadotropism following cranial irradiation (Hall JE, et al, JCEM, 1994;79(4):1166-72).
• The first documentation of the full morphologic and endocrine spectrum of normal ovulatory women with polycystic ovarian morphology only (Adams JM, et al. J. Clin. Endo. Metab. 2004 ;89(9):4343-4350.)
• The first to induce puberty in men with Idiopathic Hypogonadotropic Hypogonadism (IHH) using pulsatile GnRH administration (Hoffman AR & Crowley WF, NEJM 1982;307:1237-41; Crowley WF, et al, Rec. Prog Horm Res 1985;41:473-531).
• The initial descriptions of the dose- and frequency-responses of human pituitary LH, FSH & free alpha subunit to GnRH in men (Spratt DI, et al, JCEM 1987;64:1179-86; Spratt DI, et al, JCEM 1986;62:1136-44); Finkelstein JS, et al, JCI 1988;81:1725-33).
• The first use of free alpha subunit as a surrogate marker to GnRH action and endogenous secretion at the gonadotrope in the human and the rat (Whitcomb RW, et al, JCEM 1990;70:1654-61; Weiss J, et al, Endocrinology 1990;127:2364-71).
• The localization of the site of action and relative roles of testosterone and estradiol in the human hypothalamus and pituitary using the combined models of IHH and normals (Finkelstein JS, et al, JCEM 1991;72:609-20; Finkelstein JS, et al, JCEM 1991;72:621-28).
• The initial description that Inhibin B and its larger molecular weight precursors and not Inhibin A circulate in the human male (Lambert-Messerlian GM, et al, JCEM 1994;97:45-50; Lambert-Messerlian GM, et al, JCEM 1995;80:1541-47).
• Demonstrated that homologous desensitization of GnRH-induced stimulated LH secretion occurs within the duration of an endogenous LH pulse (Weiss J, et al, Endocrinology 1995;136:138-43).
• The identification of a hypothalamic site of estrogen negative feedback in men (Hayes FJ, et al, JCEM 2000;85:3027-35).
• The initial description of the adult-onset version of idiopathic hypogonadotropic hypogonadism IHH (Nachtigall LB, et al, NEJM 1997;336:410-15).
• The first chronicle of the longitudinal changes of Inhibin during sexual maturation in the male (Nachtigall LB, et al, JCEM 1996;81:3520-25; Seminara SB, et al, JCEM, 1996;81:3692-96).
• The description of excessive responsiveness of the free alpha subunit to GnRH in men and women with IHH (Pralong F, et al, JCEM 1995;850:3682-88; Lavoie HB, et al, JCEM 1998;83:241-42).
• The description that wide excursions of LH and of testosterone secretion outside the previously thought normal range occur in normal men (Spratt DI, et al, Am J Physiology 1998;254:E652-7).
• The first definition of the relative roles of sex steroids vs Inhibin B on FHS regulation and document the cortical importance of Inhibin tone on FSH feedback in men (Hayes FJ, et al, JCEM 2001;86:5541-46).
• The first mutation in the LH beta subunit gene in the human (Weiss J, et al, NEJM 1992;326:179-83).
• The description that X-linked Kallmann’s Syndrome accounts for the minority of cases of IHH and that both autosomal dominant and recessive forms of Kallmann’s are more common than X-linked (Waldstreicher J, et al, JCEM 1996;81:4388-93; Seminara SB, et al, Endo Rev. 1998;19:521-39).
• The first to localize a new gene responsible for non-anosmic IHH and human puberty (Acierno JS, et al, JCEM 2003;88:2947-50).
• The identification of GP54 as a major “gatekeeper” of human puberty (Seminara SB et al, NEJM 2003;349:1614-27).
In Clinical Research and Science Policy:
• The first to build a functioning clinical research infrastructure within an academic medical center (MGH) (Crowley, WF & Thier SO, Academic Medicine 1996;71:1154-63; Crowley WF & Thier SO, Academic Medicine 2001;76:700-06)
• The first to identify two ‘translational blocks’ in making basic research findings accessible to patient care (Sung N, et al, JAMA 2003;289:1278-87).
• The proposal of a funding solution for the current national crises in clinical research (Crowley WF Jr et al, JAMA 2004;291:1120-1126).
This information was copied from http://www.mgh.harvard.edu/reproendo/reu_Crowley.htm on October 14, 2006.