Dr. Miller received his undergraduate and graduate training at Dartmouth College and Dartmouth Medical School with Prs WO Berndt, G Mudge, V Ferm and W Layton in Pharmacology/Toxicology /Teratology. He also did post graduate training at Jefferson Medical College with Prs RL Brent and T Koszalka in Developmental Biology /Teratology. In 1974, he joined the Depts of Obs/Gyn at the University of Rochester under Pr HA Thiede and of Pharm/Toxicol under Pr L Lasagna as an Assistant Pr. He is currently Professor of Obs/Gyn, of Environmental Med and of Pathology and Clin Lab Med.
During this time, he has been involved with the leadership of the NIEHS Environmental Health Sciences Ctr, as well as Associate Chair for Research in Obs/Gyn. In 1987, he began the Perinatal Environmental and Drug Consultation Service (PEDECS) (now known as MotherToBaby UR Medicine) in Obs/Gyn and is its Director. This service provides advice concerning exposures during pregnancy or before pregnancy to environmental, occupational and therapeutic exposures to the women and/or famiies. He also has been co-Director of the New York State Ctr of Excellence in Children's Environmental Health at the U of Rochester.
Dr. Miller is Past President of the Teratology Society and has been active with Natl and Intl concerns involving vitamins and herbals as well as environmental exposures.
He is actively involved with OTIS, Organization of Teratology Information Specialists, with their Committees on Occupational Exposures and on Research. He is currently Chair of the Intl Committee on Research for OTIS and ENTIS, and the Society of Toxicology as Chair of its Research Funding Committee. Also he has been Scientific Director of the NIH sponsored Women's Reproductive Health Research Scholars Program for training Obs/ Gyns as Clinical Scientists at the U of Rochester from 1999-2010.
Dr. Miller is editing the 3rd ed. of "Drugs During Pregnancy and Lactation - Treatment Options and Risk Assessment".
Dr. Miller is a member of the Scientific Board of TERIS as well as a Dysmorphologist and Scientific Board Member for the US Ribavirin Pregnancy Registry and the Genentech MoTHER Pregnancy Registry.
He has been involved with a number of research programs with the National Toxicology Program (Scientific Board), the FDA, NIH, Merck, Roche, Centecor, Eastman Kodak, Johnson and Johnson and other partners. He has trained more than 25 fellows and graduate students, who are providing leadership in Academia, Government and Industry.
His funding does and has come from NICHHD, NIAID, NIAAA, NCI, NIEHS, FDA, NCS, US Israel Binational Fdn, Goode Fdn and industry partners. He was the recipient of the Bock Prize for Developmental Biology and Child Health in 2011 and received the Distinguished Service Award from the Teratology Society in 2013.
For 2013-14, he has spoken or is speaking at
• Alumni Grand Rounds Speaker, Obstetrics/Gynecology Grand Rounds, University of Rochester School of Medicine and Dentistry, Rochester, New York 2014.
• Symposium Speaker, European Network of Teratology Information Services (ENTIS) and the Organization of Teratology Information Services (OTIS) Joint Meeting II - Toronto, Canada, 2014.
• Plenary Speaker, International Federation of Placenta Association 2014 Meeting, Paris, France, 2014.
• Symposium Speaker, Teratology Society, Bellevue, Washington, 2014
• Plenary Speaker, NIH- National Children's Study Steering Committee Meeting, Bethesda, MD 2013
• Faculty, 9th NIH CICHR Summer Institute on Obstetrical Pharmacology (Toronto), 2013
• Symposium Speaker, Applied Mathematics, Modeling and Computational Science Intl. Conference -2013, Mathematics of Human Placenta: A Window into Fetal Origins of Adult Disease Waterloo, Canada, 2013
• Symposium Speaker, Teratology Society Education Course, 53rd Meeting of the Teratology Society, Tucson, AZ 2013
Perinatal Toxicology and Placentology are the foci of this laboratory. How viruses, metals (cadmium, arsenic, lead and mercury), anti-HIV therapy, and vitamins (A, B12, C and E), nanoparticles, and hyperthermia affect normal development of the embryo/ fetus are being investigated. In particular, the role of the placenta as the anchor, controller, and conduit during pregnancy as well as a site for toxic action is examined.
Placental Toxicology and Pathology.
Cadmium can be a placental toxin in rodents by producing fetal death and placental necrosis. Using an in vitro dually perfused human placenta model, cadmium also produced necrosis. Pharmacokinetic studies in both rodent and human studies demonstrated the role of the placenta as a site for control of passage and intoxication. The response of the cell to cadmium toxicity may be regulated by metallothionein and calmodulin. Different isoforms of metallothionein are being identified via cDNA isolation and in situ hybridization for determination of metallothionein distribution and indelibility in placentae from women exposed during pregnancy to environmental metals (gadolinium, cadmium, arsenic, lead and mercury). Currently gene environment interactions during development are being pursued in an animal model of diabetes mellitus.
Placental Pathology and the relationship to in utero development and adult disease is being evaluated. Focus is on specific evaluations of shape, size and vascular structure of the placenta and an understanding of the underlying pathology. These investigations are being pursued as part of an NIH National Children's Study Formative Research Study
Pregnancy loss due to implantation failures is being examined using an in vitro model consisting of both human trophoblast and endometrium to study the biology of attachment and invasion as well as the influence of hormones, xenobiotics and disease (antiphospholipid syndrome, pre-eclampsia). Additional investigations are examining the effects of plasticizers - phthalates and bisphenol A on human placental function to understand the relationship between plasticizer exposures and miscarriages.
Vertical transmission of HIV.
Why do only 25-40% of the babies of HIV positive mothers become infected? Why not all the babies? What controls infectivity of the fetus in utero? These are questions being explored in patients who are pregnant and HIV positive. In vitro models of human placenta are used to study how the placenta may modulate HIV infection in utero. Certain strains of HIV-1 can selectively infect the human placenta, while others do not. Molecular techniques are being used - Real Time - PCR, ISPCR - to determine which cells are being infected. With these models we can test how anti-HIV therapies may best prevent the vertical transmission of HIV as well as produce toxicity in the human placenta.
Preeclampsia is a major contributor to adverse pregnancy outcomes for both mother and baby. A major difficulty is diagnosing the illness before the conditions are too severe. Previous studies have demonstrated that placental growth factor and vascular endothelial growth factor levels are reduced in women who will develop severe preeclampsia. Current investigations are underway examining the clinical possibilities of early diagnosis of preeclampsia in hopes that treatment modalities will then be possible to prevent the disease.
Other investigations examine the pharmacokinetics of antiseizure, anti-HIV, ACE inhibitors, anticoagulants, nanomedicines and biotech products concerning maternal/ fetal exposures.
Barbaux S, Erwich JJ, Favaron PO, Gil S, Gallot D, Golos TG, Gonzalez-Bulnes A, Guibourdenche J, Heazell AE, Jansson T, Laprévote O, Lewis RM, Miller RK, Monk D, Novakovic B, Oudejans C, Parast M, Peugnet P, Pfarrer C, Pinar H, Roberts CT, Robinson W, Saffery R, Salomon C, Sexton A, Staff AC, Suter M, Tarrade A, Wallace J, Vaillancourt C, Vaiman D, Worton SA, Lash GE. "IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction." Placenta. 2015 Apr; 36 Suppl 1:S5-10. Epub 2015 Feb 12.
Ornoy A, Reece EA, Pavlinkova G, Kappen C, Miller RK. "Effect of maternal diabetes on the embryo, fetus, and children: Congenital anomalies, genetic and epigenetic changes and developmental outcomes." Birth defects research. Part C, Embryo today : reviews. 2015 Mar; 105(1):53-72. Epub 2015 Mar 16.
Kravchenko J, Darrah TH, Miller RK, Lyerly HK, Vengosh A. "A review of the health impacts of barium from natural and anthropogenic exposure." Environmental geochemistry and health. 2014 Aug; 36(4):797-814. Epub 2014 May 21.
Nanes JA, Xia Y, Dassanayake RM, Jones RM, Li A, Stodgell CJ, Walker CK, Szabo S, Leuthner S, Durkin MS, Moye J, Miller RK, . "Selected persistent organic pollutants in human placental tissue from the United States." Chemosphere. 2014 Jul; 106:20-7. Epub 2014 Jan 31.
2014 May 1
Ergaz Z, Guillemin C, Neeman-Azulay M, Weinstein-Fudim L, Stodgell CJ, Miller RK, Ornoy A. "Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat." Toxicology and applied pharmacology. 2014 May 1; 276(3):220-30. Epub 2014 Mar 01.