Richard K. Miller, Ph.D.

Professor R.K. Miller received his A.B. degree in Biology in 1968 from Dartmouth College, New Hampshire and his Ph.D. degree in Pharmacology and Toxicology in 1973 from the Dartmouth Medical School.

He spent two years as a postdoctoral fellow in Developmental Biology and Teratology at the Jefferson Medical College with Professors Robert L. Brent and Thomas Koszalka. He joined the University of Rochester in 1974 and is a faculty member in the Departments of Obstetrics and Gynecology, of Environmental Medicine, and of Pathology and Laboratory Medicine. In 1987, Dr. Miller became the Director of the Perinatal Environmental and Drug Consultation Service (PEDECS - a New York State Teratogen Information Service); Scientific Director of the NIH WRHR Scholars Program since 1999; he has been director of the Division of Research at the University of Rochester since 1978. In 2007, Dr. Miller was named co-Director of the New York State funded Rochester Regional Children's Environmental Health Center. From 1999 until 2006, he was Associate Chair for Research in Obstetrics and Gynecology.  In 1983, Dr. Miller was a Senior International Fogarty Scholar at the University of Paris VI, France. In 1988, Dr. Miller was named a Fulbright Distinguished Professor.

Dr. Miller is past President of the Teratology Society, founding Editor of Trophoblast Research, founding secretary of the International Federation of Placenta Associations, and is active on many NIH, NAS/NRC committees and scientific societies.

Current areas of interest:

Teratogenesis and Placental Toxicology: Reproductive and perinatal toxicology is one focus of activity of the laboratory. Teratology studies include both animal investigations concerning diabetes mellitus and ultrasound exposures as well as clinical studies identifying patient populations at risk for birth defects as part of the OTIS research consortium, e.g., isotretinoin.  Normal development of the embryo/fetus and how viruses, anti-HIV therapy, metals, and vitamins (A, B12) affect this process are being investigated.  In particular, the role of the placenta as the anchor, controller, and conduit during pregnancy as well as site for toxic action is being examined. Previous studies have demonstrated that cadmium can be a placental toxin in rodents by producing fetal death and placental necrosis. Further investigation has proven that cadmium is toxic in the human placenta using an in vitro dually perfused human placental preparation that functions well for periods of 24 hours or more. This human preparation has provided the opportunity to study the pharmacokinetics and toxicity of a number of compounds directly on the human placenta without placing either the mother or baby at risk. The objects of studies have included novel biotech molecules, immunoglobulins, ACE inhibitors, ultrasound contrast agents, nanoparticles and anticonvulsants. Investigations examined the toxicity and pharmacokinetics of other metals (arsenic, manganese, selenium, mercury, and lead) by utilizing magnetic resonance imaging/MRI and atomic absorption.  Investigations have studied the response of the cell to cadmium, a toxicity that is regulated by a metal-binding protein, metallothionein, as well as by competition with selenium and zinc. Different isoforms are being identified via cDNA isolation and in situ hybridization for determination of metallothionein distribution and inducibility in placentae from women exposed during pregnancy to environmental metals. Investigations have examined the control of cell cycle and how cadmium interferes with calmodulin in the regulation of the trophoblast cell division.

Dr. Miller has just co-edited a comprehensive text involving medicinal products both international and in the USA as well as herbal and industrial products potentially used during pregnancy.  (Drugs during Pregnancy and Lactation – Treatment Options and Risk Assessment).

HIV Vertical Transmission and Therapy:Utilizing in vitro human placental models developed in the laboratory and clinical studies in both Rochester, New York and Caracas, Venezuela, investigations of how HIV-1 infects the human placenta and how this infectivity relates to infection in the newborn are being pursued. In addition, these models are being utilized to determine which anti-HIV therapies may be most effective in reducing the vertical transmission of the HIV from mother to baby. Additional investigation has been determining not only the pharmacokinetics but also the toxicity of anti-HIV therapies and Ethanol.

Implantation Biology: Pregnancy loss due to implantation failures is another major research program. An in vitro model using human trophoblast and endometrium has been developed in this laboratory. This human model is being used to study the biology of attachment and invasion as well as the influence of hormonal therapy and xenobiotics especially metals, retinoids, phthalates and antiphospholipid antibodies / thromophilia.

Preeclampsia: Additional investigations have developed biomarkers for pre-eclampsia risk before any symptoms have appeared in the patient. Reductions of both placental growth factor and vascular endothelial growth factor in patients between 16-19 weeks of gestation are predictive of developing pre-eclampsia. Studies are initiated to study in this high risk population early in pregnancy for developing pre-eclampsia and fetal growth restriction.

Thus, this laboratory and its investigators have been concentrating their efforts upon unraveling the mechanisms by which viruses, drugs, immune responses and environmental chemicals may be producing adverse effects in the embryo/fetus, mother and especially the placenta in hopes of reducing the incidence of pregnancy loss and birth defects.

How to contact Dr. Miller:
E-Mail Address: RichardK_Miller@urmc.rochester.edu
Phone: (585) 275-2520
Link to: Environmental Medicine

Current research and publications:

• Ch. Schaefer, P. Peters and RK Miller (editors)  Drugs During Pregnancy and Lactation – Treatment Options and Risk Assessment. Academic Press, 2007.
• H Hess, RK Miller.  Herbal Medicines during Pregnancy in Ch. Schaefer, P. Peters, RK Miller (eds), Drugs during Pregnancy and Lactation,  Academic Press, pp. 485-501, 2007.
• R. K. Miller, P. Peters and P McElhatton, Occupational Industrial and Environmental Agents: Exposures during Pregnancy,  Drugs during Pregnancy and Lactation,  Academic Press. pp. 561 -608, 2007.
•   CM Salafia, J Zhang, RK Miller, AK Charles, P Shrout, W Sun.  Placenta Growth Patterns Affect Birth Weight for Given Placental Weight, Birth Defects Research A  79: 281-288, 2007
• RK Miller, P Peters, C Schaefer, General commentary on drug therapy and drug risks in pregnancy, in Ch. Schaefer, P. Peters, RK Miller (eds),   Drugs during Pregnancy and Lactation, Academic Press, pp. 2-27, 2007.
• S.D. Dertinger, R.K. Miller, K Brewer, T Smudzin, D K. Torous, D J. Roberts, S L. Avlasevich, SM Bryce, S Sugunan, and Y Chen. Automated Human Blood Micronucleated Reticulocyte Measurements for Rapid Assessment of Chromosomal Damage,  Mutation Research, 626: 111-119, 2007.
• L Trasande; J Boscarino, R Falk,  N Graber; C Schechter, G Dunkel; J Geslani;  J Moline, E Kaplan-Liss; RK Miller; K  Korfmacher,  D Carpenter; M Casalino; D Laraque; P Landrigan The Environment in Pediatric Practice: A Study of New York Pediatricians’ Attitudes, Beliefs, and Practices towards Children’s Environmental Health,  J Urban Health, 83:760-772, 2006.
• J Robertson, JE Polifka, M Avner C Chambers, G Delevan, , G Koren, S Lavigne, LP Martinez, RK. Miller, JC Carey, Failures in Isotretinoin Risk Management Programs.  Birth Defects Research A. 73: 881-887, 2005.
• RK Miller,  Does the Placenta Protect Against Insult or Is It At Target?  In Teratology Primer,  pp22-26, 2005.
• RK Miller, O Genbacev, J Aplin, M Turner, I Caniggia, B Huppertz,  Human Placental Explants in Culture: Approaches and Assessments, Placenta 26:439-48, 2005.
• SD Dertinger, K Camphausen, JT MacGregor, ME Bishop, DK Torous, S Avlasevich, S Cairns, CR. Tometsko, C Menard, T Muanza, Y Chen, RK Miller, K Cederbrant, K Sandelin, I Poten, G Bolscfoldi. Three-color labeling method for flow cytometric measurement of cytogenetic damage in rodent and human blood. Environ. Mol. Mutagenesis 44:  427-425, 2004.
• G. Ginsberg, D. Hattis, RK Miller and B Sonawane, Pediatric Pharmacokinetic Data:  Implications for Environmental Risk Assessment for Children, Pediatrics 113, 973-983, 2004.
• A Ornoy, L Chen, RM Silver and RK Miller. Maternal Autoimmune Diseases and Immunologically - Induced Embryonic and Feto-Placental Damage. Birth Defects Research A 70:371-381, 2004.
• S. Dertinger, RK Miller, C Tometsko, Micronucleated CD71-Positive Reticulocytes: A Blood-Based Endpoint of Cytogenetic Damage in Humans, Mutation Research 542: 77-87, 2003.
• G. Ginsberg, D. Hattis, RK Miller and B Sonawane, Pediatric Pharmacokinetic Data: Implications for Environmental Risk Assessment for Children, Pediatrics 113, 973-983, 2004.
• MM Miller, RK Miller, LF Battaglia, WC Dewey, MJ Edwards, WL Nyborg, C.Cox, JS Abramowicz, the D T thermal dose concept 1: in vivo teratogenesis. J. Thermal Biol. 29: 141-149, 2004.
• RK Miller, Environmental and Occupational Exposures Involving Reproduction, in P. Leppert (eds), Primary Care for Women, 2nd Edition, Lippincott, New York, 2004.
• A. Ornoy, S. Yacobi, S. Tartakover- Matalon, M Blank, Z Blumenfeld, R.K Miller, and Y.Shoenfeld. The effects of antiphospholipid antibodies obtained from women with SLE/APS and associated pregnancy loss on rat embryos and placental explants in culture. Lupus 21: 573-578, 2003.
• R.K. Miller, K. Mace, B. Polliotti, R. DeRita, W. Hall, and G. Treacy, Marginal Transfer of ReoPro™ (Abciximab) Compared with Immunoglobulin G (F105), Insulin and Water in the Perfused Human Placenta in vitro. Placenta 24: 727-738, 2003.
• R.K. Miller, K. Mace, B. Polliotti, R. DeRita, W. Hall, and G. Treacy, Marginal Transfer of ReoPro™ (Abciximab) Compared with Immunoglobulin G (F105), Insulin and Water in the Perfused Human Placenta in vitro. Placenta 24: 727-738, 2003.
• B.M. Polliotti, A.G. Fry, D.N. Saller, Jr., R.A. Mooney, C. Cox and R.K. Miller, Second-trimester maternal serum cytokines for predicting severe, early-onset pre-eclampsia. Obs/Gyn, 101:1266-1274, 2003.
• J.R. Woods, J.L. Cavanaugh, E.P. Norkus, M.A. Plessinger, and R.K. Miller, The effect of labor on maternal and fetal Vitamins C and E, Amer. J. Obs/Gyn. 187:1179-83, 2002.
• S. Yacobi, A. Ornoy, A. Blumenfeld, and R.K. Miller, The effects of sera from women with Systemic Lupus Erythematous or Antiphospholipid Syndrome and recurrent abortions on human placental explants in culture. Teratology, 66:300-308, 2002
• B.M. Polliotti, S. Gnall-Sazenski, T.S. Laughlin and R.K. Miller, Inhibitory effects of human chorionic gonadotropin (hCG) preparation on HIV infection of Human Placenta in vitro. Placenta 23: S102-106, 2002.
• R.K. Miller and L. Myatt eds, Placenta Pathobiology: HIV, Oxidant Stress and Perinatal Disease. Harcourt Press, London, UK, 2001.
• J.R. Woods, M.A. Plessinger, and R.K. Miller, Vitamins C and E: Missing links in preventing preterm premature rupture of membranes? Amer. J. Obstet. Gynecol 185:5-10, 2001.
• C.D. Chambers, S.R. Braddock, G.G. Briggs, A. Einarson, Y.R. Johnson, R.K. Miller, J. Polifka, L. K. Robinson, K. Stepanuk, K.L. Jones, Post-Marketing Surveillance for Human Teratogenicity: A Model Approach, Teratology 64;252-261. 2001
• D.A. Calhoun, N. Chegini, B.M. Polliotti, J.A. Gersting, R.K. Miller and D. Christensen. Granulocyte Colony-Stimulating Factor in preterm and term pregnancy, parturition and intra-amniotic infection. Obstetrics and Gynecology, 97(2), 229-234, 2001.
• G. Desoye, C. Sibley and R.K. Miller eds., Cell Biology and Immunology of the Placenta, Harcourt Publishers, 2000.
• O. Genbacev, R.K. Miller. Post-implantation differentiation and proliferation of cytotrophoblast cells: in vitro models--a review. Placenta 21:S45-9, 2000.
• A.U. Sheikh, B.M. Polliotti, R.K. Miller. In situ PCR detection of HIV expression in the human placenta. Methods Mol Biol. 137:75-86, 2000.
• M.A. Plessinger, J.R. Woods Jr, R.K. Miller. Pretreatment of human amnion-chorion with vitamins C and E prevents hypochlorous acid-induced damage. Am J Obstet Gynecol. 2000 Oct;183(4):979-85.
• R.K. Miller, B. Polliotti, A. Shiekh, Y. Ding, S. Reddy, K. Lord, M. Carneiro, S. Gnall, and T. Laughlin, The Role of the Placenta in the Vertical Transmission of HIV. Teratology 61: 391-4, 2000.
• A. Sheikh, B. Polliotti, and R.K. Miller. HIV Infection: In Situ PCR Localization in Human Placentae Following In Utero and In Vitro Infection. Amer. J. Obstet. Gynecol. 182: 207-13,2000.
• T.D. Zadorozhnaja, R.E. Little, R.K. Miller, N.A. Mendel , T.R. Jaylor , B.J. Presley , B.C. Gladen. Concentrations of arsenic, cadmium, copper, lead, mercury, and zinc in human placentas from two cities in Ukraine . J Toxicol Environ Health A. 61: 255-63, 2000.

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Updated July 10, 2007