Message From The Chair

Donna Ferriero, MD, MS

Children give us joy in the present and hope for the future. Here in the UCSF Department of Pediatrics, we make sure that future is as bright as possible for every infant, child and young adult struggling with illness.

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Walter L. Miller, MD



Professor Emeritus of Pediatrics

Chief, Division of Pediatric Endocrinology

Contact Info

wlmlab@ucsf.edu

Education

  • Massachusetts Institute of Technology, SB, 1965
  • Duke University, MD, 1970
  • Massachusetts General Hospital, Boston MA, PL-1 and PL-2 (Pediatrics), 1970-72
  • University of California, San Francisco, PL-3 (Pediatrics), 1974-75
  • National Heart & Lung Institute, NIH, Bethesda MD, endocrinology fellowship, 1972-74
  • University of California, San Francisco, biochemistry fellowship,1975-77
  • University of California, San Francisco, pediatric endocrinology fellowship,1977-78  

Board Certification

  • American Board of Pediatrics, 1975

Clinical Expertise

  • Pediatric endocrinology, especially adrenal and gonadal disorders of steroidogenesis

Research Interests

  • Molecular biology of steroid hormone synthesis and its disorders

UCSF Program Affiliations

  • UCSF Institute of Human Genetics
  • UCSF Biomedical Sciences Program
  • UCSF Pediatric, Adult, and Reproductive Endocrinology Training Programs
  • KURe UCSF Dept of Urology K12 Program
  • KiDS Pediatric Diabetes K12 Program

Biography

Dr. Walter L. Miller is professor emeritus of pediatrics and former chief of endocrinology at the University of California, San Francisco (UCSF). He has been an innovative international leader in pediatric endocrinology, illuminating the field of molecular steroidogenesis by integrating basic research with clinical observation. 

Dr. Miller graduated from the Massachusetts Institute of Technology in philosophy and biology in 1965. After a year working in a research lab at the Massachusetts General Hospital (MGH), he graduated from Duke University School of Medicine in 1970. He did two years of pediatric residency at the MGH (1970-72) and two years of endocrinology at the NIH in the US Public Health Service (1972-74). He then moved to UCSF where he completed his third year of residency in pediatrics (1974-75), two years of fellowship in the Department of Biochemistry and Biophysics (1975-77), and a year of fellowship in Pediatric Endocrinology (1977-78). He joined the faculty in 1978 as an assistant pofessor of pediatrics, was promoted to associate professor in 1983, to professor in 1987 and to distinguished professor in 2005. 

Dr. Miller has lectured throughout the world and served on many editorial boards, including the Journal of Clinical Endocrinology and Metabolism, DNA and Cell Biology, Endocrinology, Journal of Endocrinology, and Molecular Genetics and Metabolism.  He has been a member of NIH’s Biochemical Endocrinology Study Section and the Basil O’Connor Starter Scholar Research Award Committee of the March of Dimes, and the Board of Scientific Counselors of the National Institute of Child Health and Human Development.  He has published more than 370 papers and book chapters and, according to the Institute for Scientific Information, his work has been cited nearly 16,000 times.  He has received many awards and honors, including the Ross Research Award from the Western Society for Pediatric Research (1982), the Edwin B. Astwood Award from the Endocrine Society (1988), the Albion O. Bernstein Award from the New York State Medical Society (1993), the Clinical Endocrinology Trust Medal from the British Endocrine Societies (1993), Henning Andersen Prize from the European Society for Paediatric Research (1993), the Samuel Rosenthal Foundation Prize for Excellence in Academic Pediatrics (1999), the Clinical Investigator Award from The Endocrine Society (2006), the UCSF Distinguished Clinical Research Lectureship (2009) and the Duke University School of Medicine Distinguished Alumnus Award (2010). Dr. Miller is a member of the Society for Pediatric Research, the American Pediatric Society, the American Society for Clinical Investigation, the Association of American Physicians, the Endocrine Society, the American Society for Human Genetics, the Lawson Wilkins Pediatric Endocrine Society, and is a Fellow of the American Association for the Advancement of Science. 

http://profiles.ucsf.edu/ProfileDetails.aspx?Person=5144707

http://www.ucsf.edu/news/2011/02/8352/walter-miller-receives-dukes-distinguished-alumnus-award

http://medalum.duke.edu/modules/medalum_awards/index.php?id=34

http://www.youtube.com/watch?v=umXC0wNu1Vc

http://humgen.medschool.ucsf.edu/distinguished-memberships-honors-and-awards

http://pediatrics.medschool.ucsf.edu/millerlab/

http://nazareth.patch.com/articles/blue-eagle-foundation-inducts-four-into-wall-of-fame#photo-790

 

Current Research

Dr. Miller is internationally known for his landmark studies of the molecular biology of human steroid biosynthesis and its disorders.  His laboratory was first to clone many of the human steroidogenic enzymes, and ultimately delineated the molecular basis of several diseases, including the severe, recessive form of Ehlers-Danlos syndrome, classic and late-onset forms of congenital lipoid adrenal hyperplasia, pseudo vitamin D-deficient rickets, 17,20 lyase deficiency, P450scc deficiency, the syndrome of inappropriate antidiuresis, P450 oxidoreductase deficiency (Antley-Bixler syndrome) and a novel disorder of fetal androgen synthesis involving two AKR1C enzymes.

Dr. Miller cloned P450c17, which catalyzes both 17-hydroxylase activity (needed for cortisol synthesis) and 17, 20 lyase activity (needed for sex steroid synthesis).  By identifying the first mutations causing isolated 17,20 lyase deficiency he showed that the differential regulation of these two activities of this one enzyme is regulated by electron transfer to P450c17.  His group showed that this electron transfer is regulated post-translationally by phosphorylation of P450c17 itself and by the allosteric action of cytochrome b5.  This work explains how adrenal glucocorticoid and androgen synthesis are regulated independently, and has had an important impact on current views of the pathogenesis of the polycystic ovary syndrome. They also showed that cellular steroidogenic capacity is determined by the transcription of the gene for P450scc, the first and rate-limiting enzyme, identified the role of IGF-2 in fetal adrenal growth and discovered the extracellular matrix protein Tenascin-X as a novel gene overlapping the gene for steroid 21-hydroxylase.

The steroidogenic acute regulatory protein (StAR) mediates the acute steroidogenic response. Dr. Miller’s laboratory showed that congenital lipoid adrenal hyperplasia, a rare and severe disorder of steroidogenesis, is the human knockout of StAR, establishing its biological role.  He formulated and proved the two-hit model of this disease, explaining its baffling clinical findings.  His biophysical and cell biological analyses showed that StAR acts transiently on the outer mitochondrial membrane to facilitate the movement of cholesterol from the outer to the inner mitochondrial membrane, and that this activity requires a conformational change. His group also cloned the long-sought vitamin D-1a hydroxylase and showed that its mutations cause type 2 vitamin D-dependent rickets, discovered genetic disorders in P450scc, and, in collaboration with Drs. SM Rosenthal and SE Gitelman in UCSF Pediatric Endocrinology, discovered activating mutations in the vasopressin receptor causing the ‘syndrome of inappropriate antidiuresis’. 

Dr. Miller’s group discovered P450 oxidoreductase (POR) deficiency, a new form of congenital adrenal hyperplasia.  Miller’s group found POR mutations in patients with a broad spectrum of disease, from infants with the Antley-Bixler skeletal malformation syndrome to phenotypically normal adults with infertility. They have defined the normal human variations in POR and shown how these may affect drug metabolism. This work has established an unanticipated link between steroidogenesis, skeletal development, and pharmacogenetics. 

With a group of Swiss collaborators, Dr. Miller described the first mutations in AKR1C2 and AKR1C4, two enzymes that participate in a novel, alternative pathway of androgen synthesis. This work established, for the first time, that two separate pathways of androgen biosynthesis are required for normal male sexual development, and established a new form of disordered sexual development (DSD). 

Recent Publications (PubMed)

Last updated 10-07-2014