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Joseph H. Graziano, Ph.D.
Associate Dean for Research, Professor of Environmental Health Sciences; Professor of Pharmacology
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Research
Summary
Dr. Joseph Graziano’s research career has been devoted to understanding the consequences of exposure to metals, both on the molecular and population levels. Human exposure to metals occurs via a number of different scenarios that include exposure in the workplace; in the home, such as lead paint, or arsenic in drinking water, or outdoors; due to airborne emissions from industry or transportation vehicles. In the past, Dr. Graziano’s research was almost entirely devoted to lead poisoning, which has contributed to understanding the adverse effects of lead exposure on childhood development. As a pharmacologist, his laboratory developed the oral drug that is now used to treat children with lead poisoning. More recently, Dr. Graziano’s work has taken him to Bangladesh, where his current research is aimed at understanding the consequences of arsenic exposure on the Bangladeshi population, and on devising strategies to reduce toxicity and provide arsenic-free drinking water, a problem that spans beyond the political borders of Bangladesh, to much of South Asia, from India to Vietnam. Recent findings that both arsenic and manganese, both elevated in Bangladesh drinking water, are associated with cognitive deficits in children, add urgency to solving this enormous public health and environmental problem.
RESEARCH:
Areas of interest include: a new drug for childhood lead poisoning; environmental lead, arsenic and manganese exposure, pregnancy outcome and infant development; metal metabolism and neurodegenerative diseases.
Many diseases result from gene-environment interactions. Metals--both essential minerals and non-essential heavy metals--appear to be involved in many disease processes, most notably in the central nervous system (CNS). Dr. Graziano's laboratory is primarily interested in the consequences of metal exposure on the CNS, and is involved in studies of both early childhood development and neurodegenerative diseases in the elderly. A basic premise is that drugs and/or diet can be utilized to alter disease processes attributable to metals.
For example, his laboratory developed a highly effective oral medication for the treatment of childhood lead poisoning. The drug, 2,3-dimercaptosuccinic acid (DMSA, or Succimer), was approved by the Food and Drug Administration in 1991. Other studies concerning environmental lead exposure encompass the field of environmental epidemiology, and have elucidated the consequences of lead exposure (and of iron deficiency) on pregnancy outcome and early childhood development. Other work has utilized the technique of stable isotope dilution to experimentally determine in humans the bioavailability and toxicokinetics of lead from a variety of dietary and environmental matrices.
Dr. Graziano's lab also spent time exploring the general hypothesis that genetic or environmentally induced alterations in essential mineral metabolism may play a role in neurodegenerative diseases such as Parkinson's Disease and Alzheimer's Disease. In collaboration with Dr. Richard Mayeux, a neuroepidemiologist and Director of the Sergievsky Center, case-control studies of these diseases explored the environmental and genetic components of disease.
Current Research
1. Health Effects and Geochemistry of Arsenic and Manganese
The major goals of this project are to determine how the geochemistry of arsenic (As) and manganese (Mn) affect human exposure and examine whether such exposure is associated with adverse human health outcomes.
This proposal seeks to obtain new knowledge, and train multi-disciplinary pre- and post-doctoral students, concerning the bioavailability and/or geochemistry of As and Mn at two Superfund sites in the U.S., and areas of New Hampshire and Maine with naturally occurring As. It also encompasses epidemiologic and geochemistry studies of As and Mn in drinking water in Bangladesh which focus on carcinogenic, reproductive and childhood effects of As exposure. A Training Core coordinates multi- disciplinary education and interaction among pre- and post-doctoral trainees, who are supported by this proposal as well as another training grant. National Institute of Environmental Health Sciences (4/2006-3/2011).
2. Building Capacity to Reduce Arsenicosis in Bangladesh
The major goal of this project is to establish a multidisciplinary training program for scholars from Bangladesh to build research capacity to reduce arsenic problems.
Fogarty International Center (5/2007-2/2012).
http://www.mailmanschool.org/msphfacdir/profile.asp?uni=jg24
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Selected Publications:
1. Factor-Litvak, P, Wasserman, G, Kline, JK, Graziano, J. (1999) The Yugoslavia prospective study of environmental lead exposure. Environ Health Perspect
107:9-15
2. Wasserman, G, Factor-Litvak, P, Liu, X, Todd, AC, Kline, J, Slavkovich, V, Popovac, D, Graziano, JH. (2003) The relationship between blood lead, bone lead and child intelligence. Child Neuropsychol
9:22-34
3. Factor-Litvak, P, Hasselgren, G, Jacobs, D, Begg, M, Kline, J, Geier, J, Mervish, N, Schoenholz, S, Graziano, J. (2003) Mercury derived from dental amalgams and neuropsychological function. Environ Health Perspect
111:719-723
4. Wasserman, G, Liu, X, Parvez, F, Ahsan, H, Factor-Litvak, P, van Geen, A, Slavkovich, V, LoIacono, N, Cheng, Z, Hussain, I, Momotaj, H, Graziano, JH. (2004) Water arsenic exposure and children’s intellectual function in Araihazar, Bangladesh. Environ Health Perspect
112:1329-1333
5. Gamble, MV, Liu, X, Ahsan, H, Pilsner, JR, Ilievski, V, Slavkovic, V, Parvez, F, Levy, D, Factor-Litvak, P, Graziano, JH. (2005) Folate, homocysteine and arsenic metabolism in Bangladesh. Environ Health Perspect
113:1683-1888
6. Wasserman, G.A., Liu, X., Parvez, F., Ahsan, H., Levy, D., Factor-Litvak, P., Kline, J., van Geen, A., Slavkovich, V., LoIacono, N.J., Cheng, Z., Zheng, Y., Graziano, J.H. (2006) Water manganese exposure and children's intellectual function in Araihazar, Bangladesh. Environmental Health Perspectives
114:124-129
7. Hall, M, Chen, Y, Ahsan, H, Slavkovich, V, van Geen, A, Parvez, F, Graziano, J. (2006) Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study. Toxicology
225:225-233
8. Gamble, MV, Liu, X, Ahsan, H, Pilsner, JR, Ilievski, V, Slavkovich, V, Parvez, F, Chen, Y, Levy, D, Factor-Litvak, P, Graziano, JH. (2006) Folate and arsenic metabolism: A double-blind placebo-controlled folate supplementation trial in Bangladesh. Amer J Clin Nutr
84:1093-1101
9. Hall, M, Gamble, MV, Liu, X, Slavkovich, S, Levy, D, Cheng, Z, van Geen, A, Yunus, M, Rahman, M, Pilsner, JR, Graziano, J. (2007) Determinants of arsenic metabolism: Blood arsenic metabolites, plasma folate, B12 and homocysteine concentrations in maternal-newborn pairs. Environ Health Perspect
115:1503-1509
10. Gamble, MV, Liu, X, Slavkovich, V, Pilsner, JR, Ilievski, V, Factor-Litvak, P, Levy, D, Alam, S, Parvez, F, Ahsan, H, Graziano, J. (2007) Folic acid supplementation lowers blood arsenic. Amer J Clin Nutr
86:1202-1209
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