2020 LIFETIME ACHIEVEMENT HONOREE

DR. WALTER MILLER

Walter Miller is Distinguished Professor of Pediatrics, Emeritus, at the University of California, San Francisco, and was Chief of Endocrinology at the UCSF Benioff Children’s Hospital from 2000-2014. He also holds appointments in the Center for Reproductive Sciences and the Institute for Human Genetics. Dr. Miller received his S.B. in Philosophy from MIT in 1965 and his M.D. from Duke in 1970. After two years of pediatrics at the Massachusetts General Hospital and two years of endocrinology at the NIH, he moved to UCSF to complete his residency and do fellowships in biochemistry and pediatric endocrinology. He was appointed to the faculty in 1978, rose to Professor in 1987, was named Division Chief in 2000 and Distinguished Professor in 2005. Over his career he has published more than 430 research papers, reviews, and chapters.

Dr. Miller’s research began cloning bovine growth hormone and prolactin, but in 1983, he began studying the molecular biology of steroid hormone biosynthesis and its disorders. His group cloned the bovine gene for 21-hydroxylase, the human cholesterol side-chain cleavage enzyme, and its electron-transfer cofactors, 17-hydroxylase/17,20 lyase, and the factors responsible for placental steroidogenesis. 

His laboratory showed that gene conversion is the predominant mechanism causing congenital adrenal hyperplasia and discovered the tenascin-X gene overlapping 21-hydroxylase, and showed that Tenascin-X deficiency causes severe, recessive Ehlers-Danlos syndrome. They determined the genetic basis of congenital lipoid adrenal hyperplasia, 17-hydroxylase deficiency, isolated 17,20 lyase deficiency, and P450 oxidoreductase deficiency. His laboratory cloned the vitamin D 1-hydroxylase (CYP27B1) and showed that its mutations cause vitamin D-dependent rickets.

He collaborated in discovering activating mutations of the vasopressin receptor causing the syndrome of inappropriate antidiuresis, and in describing the first defects in the alternative ‘backdoor pathway’ of androgen synthesis showing that two pathways of androgen synthesis are needed for normal male development. 

 

More than 80 students, fellows and visiting scientists have worked in Dr. Miller’s laboratory, and another 37 have trained in Pediatric Endocrinology under his direction. Dr. Miller has received numerous awards, including the UCSF Distinguished Faculty Clinical Research Lectureship, the Duke University School of Medicine Distinguished Alumnus Award, the Judson J. VanWyk Prize for Career Achievement from The Pediatric Endocrine Society, the International Award from the European Society for Paediatric Endocrinology and the Fred Conrad Koch Award for Lifetime Achievement from the Endocrine Society. In 2018, UCSF created a Distinguished Professorship named in his honor.

2020 VISIONARY HONOREE

DR. JESUS ARGENTE

Jesús Argente is Full Professor and Chairman of Pediatrics and Pediatric Endocrinology at the University Autónoma de Madrid, Madrid, Spain and is Chief of Pediatric Endocrinology and Director of the Laboratory of Research at the University Hospital Niño Jesús in Madrid, Spain. He also holds appointments in the Institute of Food (IMDEA) and in the Biomedical Research Center on Obesity (CIBEROBN) where he is the Director of the childhood obesity program. Dr. Argente received his M.D. from the University of Zaragoza, Spain in 1980 (First in Class Award, Summa cum Laude) and his Ph.D from the University of Alcalá de Henares, Spain in 1985 (First Award of Doctoral Thesis, Summa cum Laude).

 

After four years of pediatric residency at the University Hospital Ramón y Cajal in Madrid and three years of pediatric endocrinology at the Hospital Saint-Vincent de Paul in Paris, France, he spent two years at the University of Virginia in Charlottesville as a Fulbright Postdoctoral Fellow to complete his training in endocrinology and pediatric endocrinology. He then moved to the University of Washington in Seattle where he spent two years to continue his training in molecular biology techniques applied to growth hormone regulation. He was appointed as Associate Professor at the University Autónoma de Madrid in 1989, rose to Full Professor in 2003, was named Chairman of Pediatrics & Pediatric Endocrinology in 2001.

 

Over his career, he has published more than 500 research papers, reviews, and chapters. 

During his fellowship, Dr. Argente’s research began by showing the existence of sexual dimorphism in the expression of somatostatin and growth hormone-releasing hormone in the hypothalamus of the rat during development and that somatostatin mRNA levels in the paraventricular nucleus are increased by testosterone through activation of the androgen receptor and not by aromatization to estradiol.

After returning to Madrid in 1989 and setting up a research laboratory, he was involved in the identification of patients with alterations in genes involved in human growth regulation, including GH1, GHRHR, POU1F1, PROP1, GHR, and IGFALS. His laboratory was involved in the identification of a novel class of Pseudoautosomal Region 1 deletion downstream of SHOX associated with Léri-Weill Dyscondrosteosis, as well as SHOX/PAR1duplications in the same syndrome. Later on, he discovered the first mutations in the RNPC3 gene that resulted in defective minor spliceosome activity associated to GH deficiency. Recently, his group discovered the first mutations in the metalloproteinase PAPP-A2, which selectively exerts its proteolytic activity on IGFBP-3 and IGFBP-5, which results in a new syndrome affecting growth. These patients have been shown to have an excellent response when treated with recombinant human IGF1. He collaborated in discovering mutations in the MRNK3 and DLK1 genes in Spanish patients with central precocious puberty, developing a national database of patients with this pathology in Spain. In recent years his group has developed the “Madrid Childhood Obesity Cohort” with 1,300 children with severe early-onset obesity, analyzing the molecular bases of these children and discovering new genes involved in childhood obesity. 

More than 200 hundred students, fellows, and visiting scientists have worked in Dr. Argente’s laboratory and clinic. In particular, many fellows from Spain, Mexico, Brazil, Argentina, Chile, Colombia, Bolivia, Peru, Guatemala, France, Portugal, Italy, among other countries, have trained in Pediatric Endocrinology under his direction. 

Dr. Argente has received numerous awards, including the European Society for Paediatric Endocrinology (ESPE) Henning Andersen Prize on three occasions (Vienna, Austria, 1989; Milan, Italy, 2013 and Barcelona, Spain, 2015), the ESPE Young Investigator Award (San Francisco, 1993), the Andrea Prader Award (Vienna, Austria, 2019) and many prizes from the Spanish Society for Pediatric Endocrinology (SEEP), the Spanish Society of Endocrinology (SEEN) and the Spanish Association of Pediatrics. He was inducted into the Spanish Real Academy of Medicine in 2018. 

Dr. Argente has had many lectures in more than 30 countries in Europe, America, Africa & Asia and he is ESPE Past-President (2002) and Past-President of the Spanish Society for Pediatric Endocrinology (2004-2008).