My research focuses on the potential health effects of environmental and occupational exposure to asbestos fibers,metallic nanoparticles, and carbon nanomaterials. My laboratory has developed a murine model of asbestos induced malignant mesothelioma that reproduces the morphologic and molecular characteristics of the human disease. I also collaborate with Dr. Robert Hurt in the School of Engineering to identify the physical and chemical parameters of engineered nanomaterials relevant for toxicity.

MECHANISMS OF ASBESTOS CARCINOGENESIS
Asbestos fibers persist in the lungs and cause chronic inflammation, pulmonary and pleural fibrosis, lung cancer, and malignant mesothelioma after latent periods of 20-40 years. Recent experimental evidence based on animal models using genetically-engineered mice have provided new insight about the mechanistic links between chronic inflammation, fibrosis, and cancer. Recruitment and activation of inflammatory cells in response to biopersistent fibers is accompanied by release of reactive oxygen species leading to oxidant stress, DNA damage, and mutations. Inflammatory cells can release cytokines and growth factors that stimulate stromal remodeling and angiogenesis. It is hypothesized that reciprocal activation of tumor and stromal cells facilitates growth and invasion of diffuse malignant mesothelioma. In vitro, ex vivo, and in vivo assays using well-characterized, transplantable murine mesothelial cell lines will be used to test this hypothesis. Newly-developed technologies including laser capture microdissection, cDNA microarrays, and quantitative analysis of gene expression provide powerful tools for this experimental approach.

NANOTECHNOLOGY AND NANOTOXICOLOGY
Nanotechnology is an emerging discipline with promising applications for environmental remediation at Superfund and other toxic waste sites. Airborne nanosize dusts are produced as combustion by-products and have been identified as a major contributor of adverse health effects of air pollution. New engineered nanomaterials are being developed for use as environmental sensors, in-situ catalysts for detoxification of chemical wastes, and diagnostic and drug delivery devices. The potential human health effects of occupational and environmental exposure to nanomaterials is unknown. Agnes Kane, Professor of Medical Science, and Robert Hurt, Professor of Engineering, are collaborating on an interdisciplinary research project investigating the toxicology of nanomaterials. They are working with an interdisciplinary research team of scientists, postdoctoral fellows and graduate students to synthesize and characterize model nanoparticles and to develop short-term screening assays to assess their potential toxicity.

Ongoing Research Support 
P42 ES013660 Boekelheide (PI)                                             04/18/05-06/30/15 (no cost extension)          NIH/NIEHS                                                                                                                                                  
Superfund Basic Research Program – Reuse in RI: A State-based Approach to Complex Exposures
This program has 8 research projects and 6 cores.
Role: Leader of Research Project 2 and the Training Core. The goal of Project 2 is to explore mechanisms of toxicity and genotoxicity of metallic nanoparticles and carbon nanotubes containing nickel.

T32 ES007272  Kane (PI)                                                                              07/01/02-06/30/17      NIH/NIEHS                                                                                                                                                  
Training in Environmental Pathology
The major goal of this training grant is to prepare our predoctoral and postdoctoral trainees for research careers in environment pathology and toxicology.

P200A090076 Hurt (PI), Kane (Co-PI)                                                         08/15/09-08/14/15     
US Department of Education                                                                                                                       
DOE: GAANN-Interdisciplinary Training in Applications and Implications of Nanotechnology
The goal of this training grant is to develop, administer, and evaluate a new interdisciplinary Ph.D. training program in nanotechnology, nanotoxicology, and nanomedicine.

CBET 1344097 Hurt (PI), Kane (Co-PI)                                                       11/01/13-/10/31/16
NSF
INSPIRE Track1: Computational Design for the Safe Development of High-Aspect Ratio Nanomaterials
The goal of this grant it to identify the fundamental design rules that will allow the safe development of high-aspect ratio nanomaterials.

MA-2014-01684 Boekelheide (PI), Kane and Morgan (Co-I)                       11/26/14-11/25/15
Unilever
Developing fit-for-purpose predictive biology platforms for in vitro toxicity testing
This research agreement between Brown University and Unilever support the further development and validation of unique 3-dimensional in vitro predictive biology platforms for toxicity testing.

Completed Research Support
RD-833862201 Hurt (PI) Kane (Co-PI)                                                         08/01/08-07/31/11     
EPA                                                                                                                           
Bioavailability, Environmental Transformation, and Detoxification of Core/Shell Nanomaterials
The goal of this grant was to develop and validate chemical screening assays for bioavailability assessment, data on environmental degradation, and toxicant release throughout product lifecycle.  Practical protocols for material detoxification were developed.

RO1 ES016178  Kane (PI), Hurt (Co-PI)                                                       09/20/07-05/31/12     
NIH/NIEHS                                                                                                                                                  
Chemical, Structural, and Superstructural Determinants of Nanocarbon Toxicity
The goal of this grant was to determine the properties of nanomaterials responsible for production of lung granulomas and fibrosis.

100028-D NIH Grand Opportunity Grant (RC2)                                         
Elder and Oberdorster (Co-PIs), Kane (Brown U. PI)                                    09/30/09-09/29/12     
University of Rochester (National Institute of Health)                                              
Hazard Assessment and Risk Estimation of Inhaled Nanomaterials
The goal of this grant is to address long-term consequences associated with human occupational exposures to engineered nanomaterials.

ECCS – 1057547 Hurt (PI), Kane and Pennell (Co-PIs)                                09/01/10-08/31/13      NSF                                                                                                                                                              
Exposure Pathways, Dissolution Kinetics, and Fate of Nanosilver in the Environment
The goal of this grant was to assess fate, transport, and bioaccumulation of silver nanoparticles in the aquatic environment.

CBET 1132446 Hurt (PI), Kane (Co-PI)                                                       07/01/11 – 06/30/14
NSF
Cellular and Biomolecular Interactions of Graphene-Family Nanomaterials
This interdisciplinary research project will characterize adsorption of micronutrients to a panel of well-characterized graphene-family materials and their interactions with macrophages as initial target cells using generation of reactive oxygen species and GSH depletion as endpoints.

Gulf of Mexico Research Initiative John (PI)                                                 10/01/11 – 09/30/14
Tulane University
Kane and Hurt (Co-PIs, subcontract to Brown University)
The Science and Technology of Dispersants as Relevant to Deep Sea Oil Releases
The Brown subcontract will develop novel particle-based alternatives to chemical dispersants and evaluate their potential toxicity to marine organisms.

Qiu Y, Wang Z, Owens AC, Kulaots I, Chen Y, Kane AB, Hurt RH: Antioxidant chemistry of graphene-based materials and its role in oxidation protection technology. Nanoscale 6(20): 11744-55 (2014).

Grosse Y, Loomis D, Guyton KZ, Lauby-Secretan B, El Ghissassi F, Douvard V, Benbrahim-Tallaa L, Guha N, Scoccianti C, Mattock H, Straif K; International Agency for Research on Cancer Monograph Working Group and Kane AB, Debia M, Dion C, Moller P, Savolainen K, Canu IG, Jaurand MC, Comba P, Fubini B, Kobayashi N, Morimoto Y, Tsuda H, Yu IJ, Vermeulen R, Bugge MD, Bateso TF, Kuempel ED, Morgan DL, Pinkerton KE, Sargent LM, Stayner L: Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes. Lancet Oncol. 15(13): 1427-8 (2014).

Rodd AL, Creighton MA,  Vaslet CA, Rangel-Mendez JR, Hurt RH, Kane AB:  Effects of surface-engineered nanparticle-based dispersants for marine oil spills on the model organism Artemia franciscana.  Environ Sci Technol. 48: 6419-6427 (2014).

Wang Z, von dem Bussche A, Kabadi PK, Kane AB, Hurt RH: Biological and environmental transformations of copper-based nanomaterials. ACS Nano. 7: 8715-8727 (2013).

Nel AE, Nasser E, Godwin H, Avery D, Bahadori T, Bergeson L, Beryt E, Bonner JC, Boverhof D, Carter J, Castranova V, Deshazo JR, Hussain SM, Kane AB, Klaessig F, Kuempel E, Lafranconi M, Landsiedel R, Malloy T, Miller MB, Morris J, Moss K, Oberdorster G, Pinkerton K, pleus RC, Shatkin JA, Thomas R, Tolaymat T, Wang A and Wong J: A muti-stakeholder perspective on the use of alternative test strategies for nanomaterial safety assessment. ACS Nano. 7:6422-6433 (2013).

Li Y, Yuan H, von dem Bussche A, Creighton M, Hurt RH, Kane AB, Gao H: Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites. Proc Natl Acad Sci U S A 110:12295-12300 (2013).

Creighton M, Rangel-Mendez R, Huang J, Kane AB, Hurt RH:  Graphene induced adsorptive and optical artifacts during in vitro toxicology assays . Small 9:1921-1927 (2013).

Sanchez VC, Jachak A, Hurt RH, Kane AB:  Biological interactions of graphene-family nanomaterials:  an interdisciplinary review.  Chem Res Toxicol.  25:15-34 (2012).

Liu J, Wang Z, Liu FD, Kane AB, Hurt RH:  Chemical transformations of nanosilver in biological environments.  ACS Nano. 6:9887-9899 (2012).

Jachak A, Creighton M, Qui Y, Kane AB, Hurt RH:  Biological interactions and safety of graphene materials.  MRS Bulletin 37:1307-1313 (2012).

Chen Y, Guo F, Jachak A, Kim SP, Datta D, Liu J, Vaslet C, Jang HD, Huang J, Kane A, Shenoy VB, and Hurt RH: Aerosol synthesis of cargo-filled graphene nanosacks. Nano Lett. 12: 1996-2002 (2012).

Sanchez VC, Jachak A, Hurt RH and Kane AB: Biological interactions of graphene-family nanomaterials: An interdisciplinary review. Chem. Res. Toxicol. 25:15-34 (2012).

Sanchez VC, Weston P, Yan A, Hurt RH, and Kane AB: A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials. Part Fibre Toxicol, 8, 17 (2011).

Liu X, Sen, S Liu, J Kulaots, I, Geohegan, D. Kane A, Puretzky, A, Rouleau, C, More, K, Palmore, G, and Hurt, R: (2011) Antioxidant deactivation on graphenic nanocarbon surfaces. Small 7: 2775-2785 (2011).

Shi X, von dem Bussche A, Hurt RH, Kane AB and Gao H: Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation. Nat. Nanotechnol. 6: 714-719 (2011).

Pietruska JR, Liu X, Smith A, McNeil K, Weston P, Zhitkovich A, Hurt R and Kane AB: Bioavailability, intracellular mobilization of nickel, and HIF-1α activation in human lung epithelial cells exposed to metallic nickel and nickel oxide nanoparticles. Toxicol. Sci. 124:138-148 (2011)

Broaddus VC, Everitt JI, Black B, Kane AB: Non-Neoplastic and neoplastic pleural endpoints following fiber exposure, J. Toxicol. Environ. Health, Part B Crit. Rev. 14: 153-178 (2011)

Liu X, Hurt RH, Kane AB. Biodurability of single-walled carbon nanotubes depends on surface functionalization. Carbon 48: 1961-1969 (2010).

Sarin L, Sanchez VC, Yan A, Kane AB and Hurt RH: Selenium-carbon bifunctional nanoparticles for the treatment of malignant mesothelioma. Advanced Materials. 10: 5207-5211 (2010)

Pietruska JR, Johnston T, Zhitkovich A, Kane AB: XRCC1 deficiency sensitizes human lung epithelial cells to genotoxicity by crocidolite asbestos and Libby amphibole. Environ. Health Perspect.118: 1707-1713 (2010)

Straif K, Benbrahim-Tallaa L, Baan R, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Guha N, Freeman C, Galichet L, Cogliano V: A review of human carcinogens - part C:metals, arsenic, dusts, and fibres. WHO International Agency for Research on Cancer Monograph Working Group. Lancet Oncol. 10:453-454 (2009).

Altomare DA, Menges CW, Pei J, Zhang L, Skele-Stump KL, Carbon M, Kane AB, Testa JR: Activated TNF-alpha/NF-kappaB signaling via down-regulation of fas-assocaited factor 1 in asbestos-induced mesothelioma from Arf knockout mice. Proc Natl Acad Sci U S A. 106:3420-3425 (2009).

Sanchez, VC, Pietruska JR, Miselis NR, Hurt RH, and Kane AB: Biopersistence and potential adverse health impacts of fibrous nanomaterials; what have we learned from asbestos? Wiley Interdiscip Rev, Nanomed Nanobiotechnol 1: 511-529 (2009)

Liu X, Guo L, Morris D, Kane AB, Hurt, RH: Targeted removal of bioavailable metal as a detoxification strategy for carbon nanotubes. Carbon 46: 489-500 (2008).

Miselis N, Wu Z, Van Rooijen N, Kane AB: Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesotheliomas. Mol. Cancer Ther. 7:788-799 (2008).

Guo L, von dem Bussche A, Buechner M, Kane AB, Hurt RH: Adsorption of essential micronutrients by carbon nanotubes and its implications for nanotoxicitiy testing. Small 4:721-727 (2008).

Kane AB and Hurt RH: Nanotoxicology: The asbestos analogy revisited. Nat. Nanotech. 3: 378-379 (2008).

Hoover E, Brown P, Averick M, Kane AB and Hurt R: Teaching small and thinking large: Effects of including social and ethical implications in an interdisciplinary nanotechnology course. J. of Nano Education 1: 1-10 (2008).

Guo L., Liu X., Sanchez V., Vaslet C., Kane AB., and Hurt RH: A window of opportunity: designing carbon nanomaterials for environmental safety and health. Mater. Sci. Forum 544/545:511-516 (2007).

Guo L., Morris DG., Liu X., Vaslet C., Hurt RH., Kane AB: Iron bioavailability and redox activity in diverse carbon nanotubes samples. Chem. Mater. 19:3472-78 (2007).

Pietruska JR and Kane AB: SV40 oncoproteins enhance asbestos-induced DNA double-strand breaks and abrogate senescence in murine mesothelial cells. Cancer Res. 67:3637-45 (2007).

Yan A, von dem Bussche, A, Kane AB, Hurt RH: Tocopheryl polyethylene glycol succinate as a safe, antioxidant surfactant for processing carbon nanotubes and fullerenes. Carbon 45:2463- 70 (2007).

Yan A, Lau BW, Weissman B, Kulaots I, Yang NYC, Kane AB and Hurt RH: Biocompatible, hydrophilic, supramolecular carbon nanoparticles for cell delivery. Advanced Materials. 18:2373-2378 (2006).

Kane AB: Animal models of malignant mesothelioma. Inhalation Toxicol. 18: 1001-1004 (2006).

Hurt RH, Monthioux M and Kane A: Toxicology of carbon nanomaterials: Status, trends, and perspectives on the special issue. Carbon 44:1028-1033 (2006).

Liu X., Gurel V., Morris D., Murray, D., Zhitkovich A., Kane AB., Hurt R.H. Bioavailability of nickel in single-wall carbon nanotubes. Advanced Materials 19:2790-96 (2006).

Altomare DA, Vaslet CA, Skele KL, DeRienzo A, Devarajan K, Jhanwar SC, McClatchey AI, Kane AB and Testa JR: A mouse model recapitulating molecular features of human mesothelioma. Cancer Res 65:8090-8095 (2005).

35. Altomare DA, Ramos-Nino ME, Xiao G-H, Wang HQ, Skele KL, DeRienzo AD, Mossman BT, Kane AB and Testa JR: The AKT/PKB pathway is frequently activated in human murine mesotheliomas and can be targeted to inhibit mesothelioma cell growth. Oncogene 24: 6080-6089 (2005).

Vaslet, Charles A., Messier, Norma J., and Kane, Agnes B. Accelerated progression of asbestos-induced mesotheliomas in heterozygous p53 +/- mice. Toxicological Sciences 68: 331-338 (2002).

Kane, Agnes B. Oncogenes and tumor suppressor genes in the carcinogenicity of fibers and particles. Inhalation Toxicology 12: 133-140 (2000).

Goodglick LA, Vaslet CA, Messier NJ and Kane AB, Growth factor responses and protooncogene expression of murine mesothelial cell lines. Toxicologic Pathology 25:565-573 (1997).

Macdonald JL and Kane AB. Mesothelial cell proliferation and biopersistence of wollastonite and crocidolite asbestos fibers. Fundam. Appl. Toxicol. 38:173-183 (1997).

Goodglick LA and Kane AB: Cytotoxicity of long and short crocidolite asbestos fibers in vitro and in vivo. Cancer Res. 50:5153-5163 (1990).

Moalli PA, Macdonald JL, Goodglick LA and Kane AB: Acute injury and regeneration of the mesothelium in response to asbestos fibers. Am. J. Path. 128:426-445 (1987).

Goodglick LA and Kane AB: The role of reactive oxygen metabolites in crocidolite asbestos toxicity to macrophages. Cancer Res. 46:5558-5566 (1986).

Graduated with Distinction, Swarthmore College, 1968
Phi Beta Kappa; Sigma Xi Research Society, 1968
Lucretia Mott Graduate Fellowship, 1969-1971
University Fellow of Temple University, 1971-1973
Research Career Development Award, National Institutes of Health, 1981-1986
Distinguished Teaching Award, Brown University Medical School Graduating Class, 1986, 1987
Mary Putnam-Jacobi Award, Brown University Women in Medicine, 1986
Senior Citation, Brown University Medical School Graduating Class, 1988
Honorary Citation, Brown University Association of Women Medical Faculty and the Office of Women in Medicine, 1996
Associate Editor for The American Journal of Pathology, 1992-1996
Burroughs Wellcome Visiting Professorship in the Basic Medical Sciences, 1998
Temple University School of Medicine Alumni Achievement Award, 1999
Dean's Teaching Excellence Award, Brown Medical School, 2001, 2003- 2010
De Trana Endowed Lectureship in Pathology, University of Illinois Medical School, 2004
Brown University and Women & Infants' Hospital National Center of Excellence in Women's Health, Outstanding Faculty Mentor Award, 2008
Fellow, American Association for the Advancement of Science, 2011

1993-1996 Mine Health Research Advisory Committee, National Institute of Occupational Safety and Health
1995 Scientific Advisor, International Agency for Research on Cancer, World Health Organization
1995 Invited Participant, Workshop on Chronic Inhalation Toxicity and Carcinogenicity: Testing of Respirable Fibrous Particles, U.S. Environmental Protection Agency
1996 Vice-Chair, IARC Working Group on Silica, Some Silicates, Coal Dust and Para-Aramid Fibrils
1998-1999 Invited Participant, Subcommittee on Manufactured Vitreous Fibers, Committee on Toxicology, National Academy of Sciences, National Research Council
1999 Invited Participant, IARC Working Group on the Evaluation of Foreign Bodies, Surgical Implants and Prosthetic Devices
1996-2005 Editorial Board, Toxicology and Applied Pharmacology
1996-2003 Editorial Board, The American Journal of Pathology, Toxicologic Pathology
2000 Chair, NIOSH Review Committee on Effects of Mixed Dusts on Pulmonary Inflammation, Reactivity and Susceptibility of Pulmonary Infection
2001 Chair, IARC Working Group on Man-Made Vitreous Fibres
2003 Invited Participant, Workshop on Genetically Modified Rodent Models for Cancer Hazard Identification, National Toxicology Program
2004 Invited Participant, Nanotoxicology Workshop, NSF, EPA, and NTP
2004-2005 Invited Participant, Committee on Asbestos, Institute of Medicine
2003-2007 Member of the Environmental Health Sciences Review Committee, National Institute of Environmental Health Sciences
2005 Guest Editor, Carbon
2005-present Editorial Board, The International Journal of Nanomedicine
2005 Phase I and Phase II Reviewer for Superfund Basic Research Program Grants
2005-06 Member, Committee on Asbestos: Selected Health Effects, Institute of Medicine
2006-2012 Member of the U.S. Environmental Protection Agency Science Advisory Board
2007-2008 Chair, IARC Working Group on Burden of Cancer Caused by Asbestos, World Health Organization
2007 Invited Participant, International Council on Nanotechnology (ICON) Panel to establish priorities for nanotechnology research, Zurich, Switzerland, June 5-7, 2007
2007 NanoBusiness Alliance Public Policy Tour, Washington, D.C., January 30-31, 2007
2008 Co-Chair and Organizer, Symposium on Environmental and Human Health Impacts of Nanomaterials, 236th National Meeting of the American Chemical Society, Philadelphia, Pennsylvania, August 20, 2008
2008-2012 Member of the editorial boards of Particle Fibre Toxicology and Chemical Research in Toxicology
2009 Invited Speaker, Symposium on Present and Future Directions in Nanotechnology, AAAS Annual Meeting, Chicago, February 12-16,2009
2009 Invited participant, IARC Working Group for Monograph Volume 100C on Metals, Arsenic, Dusts, and Fibres
2010 Invited Speaker and Session Chair, International Conference on Biomedical and Environmental Sciences & Technology, Beijing, China
2011 Invited Participant, Gordon Research Conference on Environmental Nanotechnology, Waterville Valley, NH
2011 Invited Participant, NSF Workshop on Nanomaterials and the Environment: The Chemistry and Materials Perspective, Arlington, VA
2011 Invited Participant, Nano Carb 11: Carbon Nanotubes and Related Materials- From Physico-Chemical Properties to Biological and Environmental Effects, Acquafredda di Maratea, Italy
2011 Distinguished Scientist Seminar Series, Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA

I am the Director of the Training Program in Environmental Pathology at Brown University, now in its 27th year of funding from the National Institute of Environmental Health Sciences. I also direct the Training Core for the Superfund Basic Research Program at Brown. In 2009, a GAANN Training Grant on Interdisciplinary Training in Applications and Implications of Nanotechnology was awarded to Brown by the U.S. Department of Education. This training grant facilitates interdisciplinary education and research for graduate students supervised by co-mentors who are actively engaged in research on the nano-bio interface, nanoscale imaging and tissue engineering, as well as the environmental and human health impacts of nanotechnology. Dr. Robert Hurt serves as Director and Dr. Agnes Kane is Co-Director. Through these training grants and my collaborative research, we are developing strategies to build new interdisciplinary research and educational initiatives in nanotechnology and nanotoxicology at Brown University. I am co-course leader with Dr. Luba Dumenco for the General Pathology course required for all first year medical students.