Joseph H. Graziano, PhD

Academic Appointments

  • Professor of Environmental Health Sciences
  • Professor of Molecular Pharmacology and Therapeutics
Joseph H. Graziano, PhD
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).
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.

Departments and Divisions

  • Department of Molecular Pharmacology and Therapeutics
  • Department of Environmental Health Sciences

NIH Grants

  • EFFECT OF EARLY-LIFE EXPOSURE TO METAL MIXTURES ON LUNG FUNCTION AND MITOCHONDRIAL DNA IN CHILDREN (Federal Gov)

    Apr 2 2019 - Mar 31 2024

    LOW-LEVEL ARSENIC EXPOSURE AND CARDIOVASCULAR DISEASE IN MULTI-ETHNIC ADULTS (MESA AS) (Federal Gov)

    Aug 1 2018 - May 31 2023

    MANGANESE-RELATED NEUROTOXICITY IN ASYMPTOMATIC WELDERS (Federal Gov)

    Mar 1 2017 - Feb 28 2022

    METALS IN THE TRIAL TO ASSESS CHELATION THERAPY 2 (TACT2) (Federal Gov)

    Oct 1 2016 - Sep 30 2021

    HEALTH EFFECTS AND GEOCHEMISTRY OF ARSENIC (Federal Gov)

    May 16 2017 - Mar 31 2021

    UNDERGRADUATE RESEARCH PROGRAM TO PROMOTE DIVERSITY IN EHS (Federal Gov)

    Apr 2 2015 - Mar 31 2020

    UNDERGRADUATE RESEARCH PROGRAM TO PROMOTE DIVERSITY IN EHS (Federal Gov)

    Apr 2 2015 - Mar 31 2020

    HEALTH EFFECTS AND GEOCHEMISTRY OF ARSENIC (Federal Gov)

    Aug 15 2017 - Mar 31 2020

    ARSENIC EXPOSURE, IMPAIRED RESPIRATORY FUNCTION, AND IMMUNOSUPPRESSION (Federal Gov)

    Jun 15 2015 - Mar 31 2020

    ARSENIC EXPOSURE, IMPAIRED RESPIRATORY FUNCTION, AND IMMUNOSUPPRESSION (Federal Gov)

    Jun 15 2015 - Mar 31 2019

    ARSENIC EXPOSURE, IMPAIRED RESPIRATORY FUNCTION, AND IMMUNOSUPPRESSION (Federal Gov)

    Jun 15 2015 - Mar 31 2019

    CEHNM - ADMIN CORE (Federal Gov)

    Jul 1 1998 - Mar 31 2018

    CEHNM - ADMIN CORE (Federal Gov)

    Jul 1 1998 - Mar 31 2018

    CEHNM - ADMIN CORE (Federal Gov)

    Jul 1 1998 - Mar 31 2018

    INTERDISCIPLINARY TRAINING IN ENVIRONMENTAL HEALTH (Federal Gov)

    Jul 1 2000 - Jun 30 2017

    INTERDISCIPLINARY TRAINING IN ENVIRONMENTAL HEALTH (Federal Gov)

    Jul 1 2000 - Jun 30 2017

    HEALTH EFFECTS AND GEOCHEMISTRY OF ARSENIC AND MANGANESE - ADMINISTRATIVE CORE (Federal Gov)

    Jun 1 2000 - Mar 31 2017

    HEALTH EFFECTS AND GEOCHEMISTRY OF ARSENIC AND MANGANESE - ADMINISTRATIVE CORE (Federal Gov)

    Jun 1 2000 - Mar 31 2017

    HEALTH EFFECTS AND GEOCHEMISTRY OF ARSENIC AND MANGANESE - ADMINISTRATIVE CORE (Federal Gov)

    Jun 1 2000 - Mar 31 2017

    FOLIC ACID AND CREATINE AS THERAPEUTIC APPROACHES FOR LOWERING BLOOD ARSENIC (Federal Gov)

    May 5 2009 - Feb 28 2017

    SOUTHEAST ASIA REGIONAL CONFERENCE ON GROUNDWATER ARSENIC: MULTI-DISCIPLINARY APPROACHES TO PROTECTING THE HEALTH OF THE PUBLIC (Federal Gov)

    Jan 1 2016 - Dec 31 2016

    BIOMARKERSFOR ARSENIC TOXICITY: GENETICS, EPIGENETICS AND FOLATE (Federal Gov)

    Feb 1 2010 - Nov 30 2016

    CHEMOPREVENTION OF ARSENIC-INDUCED SKIN CANCER (Federal Gov)

    Dec 1 2006 - Jul 31 2015

    MOLECULAR AND CLINICAL ENDOCRINE IMPACTS OF ARSENIC EXPOSURE IN CHILDREN (Federal Gov)

    Aug 1 2014 - May 31 2015

    PERKIN-ELMER NEXION-300D INDUCTIVELY COUPLED MASS SPECTROMETER (ICP-MS) (Federal Gov)

    Apr 15 2014 - Apr 14 2015

    BUILDING CAPACITY TO REDUCE ARSENICOSIS IN BANGLADESH (Federal Gov)

    Sep 29 2001 - Feb 28 2013

    WATER-BORNE MANGANESE EXPOSURE AND MOTOR FUNCTION IN YOUNG A DULTS (Federal Gov)

    Apr 15 2008 - Jan 31 2012

    ANALYSIS OF URANIUM EXPOSURE IN THE EASTERN AGENCY OF NAVAJO NATION (Federal Gov)

    Aug 28 2007 - Feb 28 2011

    CHEMOPREVENTION OF ARSENIC-INDUCED SKIN CANCER (Federal Gov)

    Dec 1 2006 - Jul 31 2010

    DENTAL AMALGAMS AND NEUROPSYCHOLOGIC FUNCTION (Federal Gov)

    Apr 1 1997 - Jan 31 2001