-- Department of Environmental Medicine --
Program in Toxicology
Post-doctoral fellows are supported by a National Institute of Environmental Health Sciences training
grant as well as by research grants.
Consult Dr. Ned Ballatori
about the current availability of these positions.
Current Postdocs |
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Radha Aras B.S. 1995, M.S. 1996 (Maharaja Sayajirao University of Baroda, India); Ph.D. 2006 (University of Southern California) E-Mail: radha_aras@urmc.rochester.edu  |
Glial–neuronal interaction: astrocytes modulate neurodegeneration in models of Parkinson’s disease The contribution of environmental toxicants to neurodegenerative diseases has been a focus of biomedical research for many years, but much remains to be learned about how these chemicals are delivered to their site of action, how their concentrations are regulated, and how they exert their neurotoxic effects in the brain. In recent years, it has increasingly been recognized that the abundance of astrocytes, their strategic organization, and close proximity to neurons provide good opportunities for intercellular exchange of molecules between these two cell types. However, the mechanism and the extent to which astrocytes are involved in regulating the levels of neurotoxic cations and thereby affecting neurodegeneration are currently unknown. The primary goal of my project is to test the hypothesis that astrocytes play a dual role in preventing and inducing neurodegeneration by regulating the levels of toxic cations available to neurons using models of Parkinson’s disease. Advisor: Kim Tieu, Ph.D. |
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Sangwoon Chung B.S. 1999, M.Sc. 2003 (Pusan National University, South Korea); Ph.D. 2007 (Kanazawa University, Japan). E-Mail: sang_chung@urmc.rochester.edu  |
Role of NIK in NF-κB signaling and chromatin remodeling Activation of nuclear factor (NF)-κB/Rel family plays a pivotal role in inflammatory response which is controlled by NF-κB-inducing kinase (NIK). NIK forms a complex with and phosphorylates IκB kinase (IKK)1 and IKK2, subsequently leading to the phosphorylation of IκB and translocation of NF-κB to the nucleus. NF-κB activation can be controlled by at two separate pathways, the canonical and non-canonical pathways, which are activated by distinct stimuli via distinct IKK complexes. Among these pathways, non-canonical pathway stimulates a complex of NIK and IKKα, resulting in the phosphorylation-coupled proteolysis of 100 κDa NF-κB2 to form the activated 52 kDa NF-κB2-RelB complex. We hypothesized that cigarette smoke, oxidants and aldehydes via NIK, activate IKK1 which, though interaction with CREP-binding protein (CBP), is able to induce histone H3 acetylation-chromatin modifications on pro-inflammatory promoters. This acetylation allows the RelA/p65 to bind DNA and transcribe pro-inflammatory cytokines. Also, we are investigating whether RelB pathway contribute to histone acetylation and chromatin modifications in a variety of cells, e.g. lymphoid B & T cells, macrophages and lung epithelial cells by cigarette smoke. Advisor: Irfan Rahman, Ph.D. |
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Mei Cui M.D. 2002 (Shanxi Medical University, China) Ph.D. 2006 (Neurology, Fudan University, China) E-Mail: mei_cui@urmc.rochester.edu  |
Assessment of function and gene-environment interaction of mutant parkinsonian genes. In recent years several genetic mutations have been discovered in Parkinson’s disease. Our aim is to create stable cell lines with inducible over-expression of these mutated genes and their wild type counterparts. These stable cells will be used to assess how the mutated genes induce neuronal dysfunction and neurodegeneration in the presence or absence of environmental neurotoxicants. I will also determine how these diverse forms of mutations would lead to the common type of dopaminergic cell death as seen in Parkinson’s disease. Advisor: Kim Tieu, Ph.D. |
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Christine Hammond B.S. 1998 (Allegheny College); Ph.D. 2004 (University of Rochester) E-Mail: christine_hammond@urmc.rochester.edu  |
Mechanisms of glutathione transport. The initial step in reduced glutathione (GSH) turnover in all mammalian cells is its transport across the plasma membrane into the extracellular space; however, the mechanisms of GSH transport are not clearly defined. GSH export is required for the delivery of its constituent amino acids to other tissues, detoxification of drugs, metals, and other reactive compounds of both endogenous and exogenous origin, protection against oxidant stress, and secretion of hepatic bile. Abnormal intracellular GSH levels that may arise from increased or decreased GSH transport have been associated with a variety of human diseases. For example, some cancerous tumors are known to have elevated GSH levels, and in diseases where increased apoptosis is observed—such as Alzheimer’s disease, Parkinson’s disease, and a variety of autoimmune disorders—low levels of intracellular GSH are observed in affected cells. Currently, our studies are focused on determining the mechanism behind GSH export during apoptosis. Our hypothesis is that MRP1, a known GSH transporter, is responsible for the drastic reduction in GSH during apoptosis. Increasing our understanding of GSH extrusion during apoptosis may help determine why certain cell populations are vulnerable to disease and help prevent or treat these diseases. Advisor: Ned Ballatori, Ph.D. |
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Jae-woong Hwang B.S. 2000; Ph.D. 2008 (Seoul National University, South Korea). E-Mail: jae-woong_hwang@URMC.rochester.edu  |
Role of SIRT1 in cigarette smoke-induced autophagy. Human sirtuin (SIRT1) is essential for maintaining silent chromatin via the deacetylation of proteins including non-histones and histones. SIRT1 plays an important role in a wide variety of processes, including stress resistance, metabolism, apoptosis, senescence, differentiation, and aging. SIRT1 regulates cigarette smoke-induced inflammation, and cigarette smoke causes oxidative stress which is now known to be responsible for triggering inflammatory events and apoptosis in the lungs of smokers/COPD patients. Oxidative stress is implicated in autophagy and SIRT1 has a role in regulation of autophagy. Autophagy is a general term for the degradation of cytoplasmic components within lysosomes and is important for various physiological and pathophysiological processes. My research interest is to study the role of SIRT1 in role of cigarette smoke-induced autophagic cell death in lung cells, and its relevance to human COPD. Advisor: Irfan Rahman, Ph.D. |
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Hiromi Ishitobi B.A. 2001; Ph.D. 2003 (University of Tokyo) E-Mail: hiromi_ishitobi@urmc.rochester.edu  |
Neurotoxic effects of prenatal joint exposure to methylmercury and inorganic mercury. Mercury toxicity is the focus of substantial public concern. Many populations are exposed to more than one form of mercury. However, how different species of mercury act in combination is not known. The two predominant forms of mercury in our environment, methylmercury from fish, and inorganic mercury in the form of mercury vapor, are both neurotoxicants. We are investigating the effects on neurodevelopment of joint exposure during the prenatal period to these two mercury species, based on the proposition that such joint exposures have the potential to modify the developmental neurotoxicity of exposure to either species in isolation. Advisor: Bernard Weiss, Ph.D. |
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Guangbi Jin B.S. 1987 (Bethune Medical University, Changchun, China); Ph.D. 2003 (University of Tokyo) E-Mail: guangbi_jin@urmc.rochester.edu  |
Role of aryl hydrocarbon receptor (AhR) activation in antigen-presenting cell function. My research interest is the role of aryl hydrocarbon receptor (AhR) activation in antigen-presenting cell function that results in diminished clonal expansion and differentiation of influenza virus-specific CD8+ T cells. AhR is a ligand-activated transcription factor that is expressed in cells of the immune system. The pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is the most potent AhR agonist known, and is also a well known immune suppressant. However, the precise molecular mechanism remains unclear. We have previously shown that AhR activation by TCDD suppresses the proliferation and differentiation of influenza virus-specific CD8+ T cells. However, TCDD does not affect CD8+ T cells directly, suggesting that defects in other cells essential for activating CD8+ T cells are affected by AhR activation. I am currently testing the hypothesis that exposure to TCDD will affect the functions of dendritic cells. Advisor: B. Paige Lawrence, Ph.D. |
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Michael D. Laiosa B.S. 1997 (SUNY-Geneseo); Ph.D. 2002 (Upstate Medical University) E-Mail: michael_laiosa@urmc.rochester.edu  |
Immune system modulation by environmental toxicants. My research concerns how toxic agents in the environment interact with our genes to modulate normal biological outcomes, particularly those pertaining to the immune system, autoimmunity, and cancer. Currently, the heavy metal mercury is serving as a model to interrogate lymphocyte signaling, death and regulation of self tolerance. We have found that mercury modulates T-lymphocyte activation and apoptosis in response to antigenic challenge in vivo. Moreover, we have genetic and toxicological evidence supporting a role for the death receptor pathway CD95 in these processes. Advisor: Michael J. McCabe, Jr., Ph.D. |
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Geniece Lehmann, Ph.D. B.A. 1998 (St. John Fisher College); Ph.D. 2006 (University of Rochester) E-Mail: geniece_mccollum@urmc.rochester.edu  |
Environmental ligands, autoimmunity and adipogenesis in the human orbit. A common complication of Graves’ hyperthyroidism is Graves’ ophthalmopathy (GO). In GO, activated T cells are recruited to the orbit, where they release proinflammatory cytokines and prostaglandins. These mediators activate orbital fibroblasts, resulting in extraocular muscle hypertrophy, extracellular matrix deposition and accumulation of fat. The increased volume of the orbital tissue forces the eyeball to protrude from the bony orbit, resulting in undesirable consequences to eye function. Fibroblasts within the orbital tissue of patients with Graves’ disease, major mediators of GO, are exquisitely sensitive to activation by T cell infiltration, peroxisome proliferator-activated receptor (PPAR)-gamma stimulation, and exposure to cigarette smoke extract and aryl hydrocarbon receptor (AhR) ligands, both exogenous and endogenous. The sensitivity of Graves’ orbital fibroblasts to cigarette smoke, which contains AhR ligands, is especially interesting because Graves’ patients who smoke are more likely to develop GO, and the course of their disease tends to be more severe than that of non-smokers. The present studies utilize T cells and orbital fibroblasts from normal humans and those with Graves’ hyperthyroidism to address the hypothesis that cigarette smoke and other sources of environmental AhR ligands exaggerate the response of Graves’ orbital fibroblasts to T cell infiltration and PPAR-gamma stimulation, resulting in the increased accumulation of fatty tissue that is seen in GO patients. Advisor: Richard Phipps, Ph.D. |
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Betina J. Lew B.A. 1988 (São Paulo State University, Brasil); M.Sc. 1993 (The Hebrew University of Jerusalem, Israel); Ph.D. 2005 (São Paulo State University and Michigan State University) E-Mail: betina_lew@urmc.rochester.edu  |
Toxicology in mammary gland development and lactation I am studying the physiological, morphological, and molecular mechanisms by which pollutants alter mammary gland development during pregnancy and how these changes affect lactation in mammals. Specific focus is currently on the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin — TCDD or dioxin. This development is a complex and tightly orchestrated process involving numerous hormones, growth factors, extra cellular matrix (ECM) components, and other molecules produced locally in the mammary gland as well as in other glands and tissues. Dioxins bind and activate the aryl hydrocarbon receptor (AhR). AhR activation impairs mammary development during pregnancy, thereby blocking normal gland function during lactation. Advisor: B. Paige Lawrence, Ph.D. |
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Ravikumar Manickam B.V.Sc., 1992; M.V.Sc., 1994, Madras Veterinary College, Chennai, India; Ph.D. 2006, Roslin Institute, Edinburgh, United Kingdom E-Mail: ravikumar_manickam@urmc.rochester.edu  |
TCDD impairs mammary gland differentiation and lactogenesis 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD/Dioxin) has recently been reported to affect the mammary gland differentiation and lactogenesis in mice. However, very little is known about the cellular and molecular mechanism by which TCDD affects mammary gland differentiation and lactogenesis. Dioxin binds with high affinity to the aryl hydrocarbon receptor (AhR) and translocates to the nucleus, affecting gene expression and cellular function. The AhR and its partner the AhR nuclear translocator (ARNT) are also present in the mammary tissues. This leads to the hypothesis that AhR activation during pregnancy might disrupt the normal cellular signaling that directs pregnancy-associated mammary gland development and milk proteins gene expression, resulting in impaired mammary epithelial cells differentiation and lactation. I’m currently involved in elucidating the cellular and molecular mechanisms by which TCDD impairs milk proteins gene expression, and identifying the role of AhR in altered mammary epithelial cells differentiation and function. Advisor: B. Paige Lawrence, Ph.D. |
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Saravanan Rajendrasozhan B.S. 1999 (University of Madras, India); Ph.D. 2006 (Annamalai University, India) E-Mail: saravanan_rajendrasozhan@urmc.rochester.edu  |
Role of sirtuin (SIRT1) in cigarette smoke-mediated lung injury and inflammation. Chronic Obstructive Pulmonary Disease (COPD) continues to cause a heavy health and economic burden both in the United States and around the world. Cigarette smoke is a important trigger of oxidative stress and inflammation in COPD by a mechanism mediated via pro-inflammatory gene transcription. Histone acetylatases are the key regulators of the specificity and duration of this gene transcription. In our lab, we found out that class III histone deacetylases (sirtuin) were decreased in reasponse to cigarette smoke exposure both in vitro and in vivo. This was correlated with the increased release of pro-inflammatory cytokines. My research concerns how sirtuin is decreased in response to cigarette smoke exposure and how it regulates the pro-inflammatory cytokine release. Moreover, we are investigating whether regulation of sirtuin can control the progression of inflammation/COPD, which is measured both in vitro, with human airway epithelial cells and macrophages, and in vivo, with genetic sirtuin knockout mice. Advisor: Irfan Rahman, Ph.D. |
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Amber Rinderknecht B.A. 1998 (Emory University ); Ph.D. 2005 (University of California, Irvine) E-Mail: amber_rinderknecht@urmc.rochester.edu  |
Translocation and toxicological effects of inhaled nanoparticles. Nanotechnology is a burgeoning field and includes the use of nanoparticles for biomedical, industrial, and consumer applications. Because of the large surface area and vast underlying vasculature offered by the lung epithelium, particle accessibility to systemic circulation following pulmonary exposure generates great concern. However, little focus has been given to the toxicological and inflammatory responses that result from exposure to these nanoengineered particles. My research studies how particle surface-functionalization, size and dose greatly influence sight-specific inflammation, whole-body translocation, and cardiovascular injury after exposure through the respiratory system. Advisor: Günter Oberdörster, Ph.D. |
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Isaac Kirubakaran Sundar B.Sc. 2000 (University of Madras, India); M.Sc. 2002, (Periyar University, India); Ph.D. 2007 (Pondicherry University, India) E-Mail: isaac_sundar@urmc.rochester.edu  |
Epigenetic regulation of lung inflammation. Epigenetics is the term used to describe heritable changes in gene expression that are not coded in the DNA sequence itself but by post-translational modifications in DNA and histone proteins. These modifications include histone acetylation, deacetylation and methylation. Aging, diet, environmental exposures and other stresses can cause epigenetic alterations, resulting in cancer or other chronic inflammatory diseases, such as COPD, asthma, and pulmonary fibrosis. The aim of our research is to determine the molecular mechanisms of epigenetic alterations via IKKalpha and MAP kinase pathways in response to environmental oxidants, such as cigarette smoke (CS). Understanding the intracellular signaling pathways involved in epigenetic regulation of lung inflammation will allow us to identify therapeutic targets for many chronic inflammatory lung diseases and cancer. Advisor: Irfan Rahman, Ph.D. |
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Hongwei Yao Master of Medicine 2000; Ph.D. 2003 (Zhejiang University, China) E-Mail: hongwei_yao@urmc.rochester.edu  |
Role of NADPH oxidase in cigarette smoke–induced inflammation in mice. Increased oxidative stress, due to either inhaled or endogenously-generated oxidants, occurs in cigarette smoke-induced lung injury and inflammation. NADPH oxidase is the main cellular source of reactive oxygen species (ROS) in mononuclear and granulocytic leukocytes. It is composed of five subunits, p40phox (phox for phagocytic oxidase), p47phox, p67phox, p22phox, and gp91phox. We hypothesized that targeted ablation of components of NADPH oxidase (p47phox-/- and gp91phox-/-) would protect lungs against detrimental effects of cigarette smoke (CS) by not generating endogenous ROS. To test the hypothesis, we are studying the effects of CS (acute and chronic exposures) and assessing the oxidative and inflammatory responses in lungs of these mice. Advisor: Irfan Rahman, Ph.D. |