Costa Lab

Costa_photo

Max Costa, Ph.D.

Professor, Department of Environmental Medicine (Chair) and Biochemistry and Molecular Pharmacology

Program Director of the Environmental and Molecular Carcinogenesis Program, NYU Cancer Institute  

Contact Info:

Address: 57 Old Forge Road, Tuxedo, NY 10987
Phone: 845-731-3515
Email: Max.Costa@nyumc.org

 

Key Interests

Epigenetics, Metal Carcinogenesis, Histone Modifications, Histone demethylases, ssUVR

Biographic Details:

Graduate Education: 1976 Ph.D. in Pharmacology from the University of Arizona Medical School, Tuscon, AZ, Graduate Education

Postdoctoral Training: 1976-1977 University of Arizona Medical School in Tuscon

Academic Appointments:

1977-79 Assistant Professor of Laboratory Medicine, University of Connecticut School of Medicine, Farmington, CT

1979-80 Assistant Professor, Department of Pharmacology and Toxicology, College of Medicine, Texas A & M University, College Station, TX

1980-81 Assistant Professor, Department of Pharmacology, The University of Texas Medical School, Houston, TX

1985-86 Associate Professor (with tenure), Department of Pharmacology, The University of Texas Medical School, Houston, TX

1985-86 Professor (with tenure), Department of Pharmacology, The University of Texas Medical School, Houston, TX

1986-93 Deputy Director, Institute of Environmental Medicine, New York University Medical Center

1986- Professor of Environmental Medicine and Pharmacology (with tenure), New York University Medical Center

1993- Professor and Chairman, Department of Environmental Medicine, NYU School of Medicine

Major Responsibilities:
Train graduate students, conduct extramurally funded research and Chair the Department of Environmental Medicine.

Major Honors:

Recipient of the Kenneth Morgareidge Award in 1984.  This award is given for an outstanding contribution to toxicology by individuals under the age of 36 who are working in academic, government or industrial institutions throughout the world (includes a $5,000 cash prize).  Sponsored by the International Life Sciences Institute

Medical College of Wisconsin, Distinguished Speaker for the Cancer Center, Milwaukee, WI, June, 1994

Burroughs Welcome Visiting Professor in the Basic Medical Sciences and Distinguished Scientist Speaker, University of South Alabama, College of Medicine, January, 1996

Recipient of a medal from the President of the University of Modena, Modena, Italy in recognition of scientific achievement (1997)

Recipient of Lifetime Achievement award from the Metals Specialty Section of the Society of Toxicology, Salt Lake City 2010

Research Interests:

Water insoluble nickel compounds vary in their carcinogenic potency due to a selectivity in the ability of the particles to be phagocytized by target cells. In the acidified phagosomes, ionic nickel is released, ultimately making its way into the nucleus.  Ni ions cause an increase in DNA methylation we believe by inhibiting Fe dependent histone demethylases such as those responsible for demethylating H3K9 mono and dimethyl.  This results in gene silencing.  Nickel ions also inhibit the Jarid-1 family of histone demethylases which result in an increase in H3K4 trimethylation causing genes to be turned on.  The dioxygenase superfamily of enzymes are the major targets for nickel ions in cells and one member of this family are the prolyl hydroxylases that cause hypoxia inducible factor (HIF-1 alpha) to be degraded.  Inhibition of these dioxygenases by nickel ions stabilizes HIF-1 alpha and turns on or off all HIF-1 alpha dependent genes.  We have used ChIP-on-chip as well as ChIP-seq to map the H3K4 trimethylation changes in the genome and correlated this with RNA expression using RNA-seq.  We have determined the binding constant of JHDM2A for Ni ions to be 1.7uM which is three times better than that for Fe which is bound to the active site of the enzyme.  Using X-ray photo-electron spectroscopy we have determined that Ni ions bind in place of Fe to exactly the same ligands as Fe in the active site of the enzyme.  Knockdown of JHDM2A as well as nickel ion treatment results in the transformation of BEAS-2B cells to anchorage independent growth.  Sprly2 and Cldn1 are down regulated by Ni inhibition of JHDM2A and these genes remain silenced after nickel is removed and in the nickel transformed cells. Forced expression of Sprly2 prevents ni ion induced cell transformation and tranfection of Cldn1 reverses cell transformation induced by nickel ions.  Our goal of these studies is to prove that the inhibition of a histone demethylase JHDM2A by Ni ions is responsible for cell transformation.

Selected Publications:

Wu F, Sun H, Kluz T, Clancy HA, Kiok K, Costa M. Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol 2012;258(2):166-175. PMCID: PMC3259276

Chervona Y and Costa M. Hexavalent Chromium and Cancer. In: Encyclopedia of Metalloproteins, Uversky VN, Kretsinger RH, Permyakov EA (eds). Springer Science 2012

Arita A, Niu J, Qu Q, Zhao N, Ruan Y, Nadas A, Chervona Y, Wu F, Sun H, Hayes RB, Costa M. Global levels of histone modifications in peripheral blood mononuclear cells of subjects with exposure to nickel. Environ Health Perspect. 2012:120(2):198-203. PMCID: PMC3279455

Muñoz A, Costa M. Elucidating the mechanisms of nickel compound uptake: A review of particulate and nano-nickel endocytosis and toxicity. Toxicol Appl Pharmacol. 2012;260(1):1-16. PMCID: PMC3306469

Wojcik OP, Koenig KL, Zelenich-Jacquotte A, Pearte C, Costa M, Chen Y. Serum taurine and risk of coronary heart disease: a prospective, nested case-control study. Eur J Nutr. 2012 Feb 10. [Epub ahead of print] 2013;52(1):169-78. PMCID: PMC3920833

Chervona Y, Costa M and Dai W. Epigenomics: Pioneering a New Frontier in Cancer Research. Pharmacogenom Pharmacoproteomics 2012;3:1

Chervona Y, Arita A and Costa M. Carcinogenic metals and the epigenome: understanding the effect of nickel, arsenic, and chromium. Metallomics 2012;4:619-627. PMCID: PMC3687545

Clancy HA, Sun H, Passantino L, Kluz T, Muñoz A, Zavadil J, Costa M. Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer. Metallomics. 2012;4(8):784-93. PMCID: PMC3563094

Arita A, Shamy MY, Chervona Y, Sun H, Hall MN, Gamble MV, and Costa M. The effect of exposure to carcinogenic metals on histone tail modifications and gene expression in human subjects. ISTERH Conference Proceedings; J Trace Elem Med Biol 2012;2:174-178

Chervona Y and Costa M. Carcinogenic metals alter histone tail modifications. Toxicology and Epigenetics First Edition. Edited by Saura C. Sahu. John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

Zuo Z, Ouyang W, Li J, Costa M, and Huang C. Cyclooxygenase-2 (COX-2) Mediates Arsenite Inhibition of UVB-Induced Cellular Apoptosis in Mouse Epidermal C141 Cells. Curr Cancer Drug Targets 2012;12:607-616

Khodeir M, Shamy M, Alghamdi M, Zhong M, Sun H, Costa M, Chen L-C, Maciejczyk P. Source apportionment and elemental composition of PM2.5 and PM10 in Jeddah City, Saudi Arabia. Atmos Pollut Res 2012;3 331-340

Chervona Y, Costa M. The control of histone methylation and gene expression by oxidative stress, hypoxia and metals. Free Radic Biol Med 2012;53 1041-1047. PMCID: PMC3432141

Chervona Y, Hall MN, Arita A, Wu Y, Sun H, Tseng H-C, Ali E, Uddin MN, Liu X, Zoroddu MA, Gamble MV, Costa M. Association Between Arsenic Exposure and Global Post-translational Histone Modifications Among Adults in Bangladesh. Cancer Epidemiol, Biomarkers Prev 2012;21:2252-2260. PMCID: PMC3518638

Arita, A. and Costa, M. Current Technology for Assessing Epigenetic Marks and their Utilization in the Study of Metal Carcinogenesis. In: Subhrangsu S. Mandal (Ed.) Recent Trends in Gene Expression, pp. 239-258, Nova Publishers 2012

Clancy, H. and Costa, M. Nickel A Pervasive Carcinogen. Future Oncology Vol 8 pp1507-1509 (2012)

Sun H, Shamy M, Kluz T, Muñoz AB, Zhong M, Laulicht F, Alghamdi MA, Khoder MI, Chen LC, Costa M. Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia. Toxicol Appl Pharmacol. 2012;265(2):147-57. PMCID: PMC3883356

Arita A, Muñoz A, Chervona Y, Niu J, Qu Q, Zhao N, Ruan Y, Kiok K, Kluz T, Sun H, Clancy HA, Shamy M, Costa M. Gene expression profiles in peripheral blood mononuclear cells of chinese nickel refinery workers with high exposures to nickel and control subjects. Cancer Epidemiol Biomarkers Prev 2013;22(2):261-9. PMCID: PMC3565097

Passantino L, Costa M and Matsui M (2013). Skin Cancer Prevention Strategies. In: Highlights in Skin Cancer, Dr. Pierre Vereecken (Ed.), ISBN: 978-953-51-1073-6, InTech, Available from: http://www.intechopen.com/books/highlights-in-skin-cancer/skin-cancer-prevention-strategies

Giri NC, Passantino L, Sun H, Zoroddu MA, Costa M, Maroney MJ. Structural Investigations of the Nickel-Induced Inhibition of Truncated Constructs of the JMJD2 Family of Histone Demethylases Using X-ray Absorption Spectroscopy. Biochemistry. 2013;52:4168-4183. PMCID: PMC3746964

Brocato, J. and Costa, M. Basic mechanics of DNA methylation and the unique landscape of the DNA methylome in metal-induced carcinogenesis. Crit Rev Toxicol 2013:43:493-514. PMCID: PMC3871623

Muñoz, A and Costa M. Nutritionally Mediated Oxidative Stress and Inflammation. Oxid Med Cell Longev 2013;2013:610950. PMCID: PMC3697417

Passantino, L, Muñoz, AB, and Costa M. Sodium metavanadate exhibits carcinogenic tendencies in vitro in immortalized human bronchial epithelial cells. Metallomics 2013;5(10):1357-1367. PMCID: PMC3982314

Sun H, Shamy M and Costa M. Nickel and Epigenetic Gene Silencing. Genes 2013;4:583-595. PMCID: PMC3927569

Vuskovic M, Barbuti AM, Goldsmith-Rooney E, Glassman L, Bovin N, Pass H, Tchou-Wong K-M, Chen M, Yan B, Niu J, Qu Q, Costa M, and Huflejt M. Plasma Anti-Glycan Antibody Profiles Associated with Nickel level in Urine. J Proteomics Bioinform 2013;6: 302-312. PMCID: PMC3984841

Costa M. Dioxygenases as Targets of Metals, Hypoxia and Oxidative Stress during Carcinogenesis. J Mol Genet Med 2013, 7:3

Brocato J, Chervona Y and Costa M. Molecular Responses to Hypoxia-Inducible Factor 1α and Beyond. Mol Pharmacol 2014;85:651-657. PMCID: PMC3990019

Brocato J, Costa M. 10th NTES Conference: Nickel and arsenic compounds alter the epigenome of peripheral blood mononuclear cells. J Trace Elem Med Biol 2014 Apr 19. pii: S0946-672X(14)00057-1. doi: 10.1016/j.jtemb.2014.04.001. [Epub ahead of print]. PMCID: PMC4201979

Yao Y, Des Marais TL and Costa M. Chromatin memory in the development of human cancers. Gene Technol 2014;3(2):114. PMCID: PMC4297643

Yao Y and Costa M. Toxicogenomic effect of nickel and beyond. Arch Toxicol 2014;88:1645-1650. PMCID: PMC4134377

Davidson T, Ke Q and Costa M. "Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity." In: Nordberg GF, Fowler BA and Nordberg M eds. Handbook on the Toxicology of Metals. Fourth ed. Vol. I. Waltham, MA: Academic Press, 2015. 173-196

Laulicht F, Brocato J, Ke Q and Costa M. "Carcinogenicity of Metal Compounds." In: Nordberg GF, Fowler BA and Nordberg M eds. Handbook on the Toxicology of Metals. Fourth ed. Vol. I. Waltham, MA: Academic Press, 2015. 351-378

Langård S and Costa M. "Chromium." In: Nordberg GF, Fowler BA and Nordberg M eds. Handbook on the Toxicology of Metals. Fourth ed. Vol. II. Waltham, MA: Academic Press, 2015. 717-742

Klein C and Costa M. "Nickel." In: Nordberg GF, Fowler BA and Nordberg Meds. Handbook on the Toxicology of Metals. Fourth ed. Vol. II. Waltham, MA: Academic Press, 2015. 1091-1111

Des Marais TL and Costa M (October 2014) Genotoxicity and Epigenetic Modifications in Response to Atmospheric and Engineered Nanoparticles. In: Encylopedia Life Sci (eLS). John Wiley & Sons, Ltd: Chichester. DOI: 10.1002/9780470015902.a0025833

Brocato J, Fang L, Chervona Y, Chen D, Kiok K, Sun H, Tseng H, Xu D, Shamy M, Jin C, and Costa M. Arsenic Induces Polyadenylation of canonical histone mRNA by down regulating stem-loop binding protein gene expression. J Biol Chem 2014;289(46):31751-31764. PMCID: PMC4231654

Cartularo L and Costa M. Role of Iron in Epigenetic Regulation of Gene Expression. In: Ho E and Domann F eds. Nutrition and Epigenetics. Boca Raton: CRC Press, 2014. 253-271

Arita A and Costa M. Oxidative Stress and the Epigenome in Human Disease. J Genet Genome Res 2014;1:2

Brocato J, Sun H, Shamy M, Kluz T, Alghamdi MA, Khoder MI, Chen LC, Costa M. Particulate matter from Saudi Arabia induces genes involved in inflammation, metabolic syndrome and atherosclerosis. J Toxicol Environ Health A 2014;77(13):751-766. PMCID: PMC4233653

Brocato J and Costa M. SATB1 and 2 in Colorectal Cancer. Carcinogenesis 2015;36:186-191. PMCID: PMC4400443

Xiao C, Xie C, Tu W, Xia Y, Costa M and Zhou X. Cadmium induces histone H3 lysine methylation by inhibiting histone demethylase activity. Toxicol Sci 2015 Feb 10. pii: kfv019. PMCID: PMC4833035

Niu Y, Des Marais T, Tong Z, Yao Y, Costa M. Oxidative stress alters global histone modification and DNA methylation. Free Radical Biol Med 2015;82:22-28. PMCID: PMC4464695

Muñoz A, Chervona Y, Hall M, Kluz T, Gamble MV, Costa M. Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water. Toxicol Appl Pharmacol http://dx.doi.org/10.1016/j.taap.2015.02.025. PMCID: PMC4410068

Gesumaria L, Matsui MS, Kluz T, Costa M. Solar-simulated ultraviolet radiation induces histone 3 methylation changes in the gene promoters of matrix metalloproteinases 1 and 3 in primary human dermal fibroblasts. Exp Dermatol 2015;24(5)384-5. PMCID: PMC4471858

Brocato J, Chen D, Liu J, Fang L, Jin Chunyuan, Costa M. A potential new mechanism of arsenic carcinogenesis: depletion of stem-loop binding protein and increase in polyadenylated canonical histone h3.1 mRNA. Biol Trace Elem Res 2015 Apr 21. [Epub ahead of print] PMCID: PMC4470754

Laulicht F, Brocato J, Cartularo L, Vaughan J, Wu F, Kluz T, Sun H, Oksuz BA, Shen S, Peana M, Medici S, Zoroddu MA, Costa M. Tungsten-induced carcinogenesis in human bronchial epithelial cells. Toxicol Appl Pharmacol. 2015 Jul 9;288(1):33-39. doi: 10.1016/j.taap.2015.07.003. PMCID: PMC4579035. [Available on 2016-10-01]

See All Publications

Lab Members:

Hong Sun
Thomas Kluz
Jason Brocato
Laura Cartularo
Yana Chervona
Freda Laulicht
Alexandra Munoz
Lisa Passantino