Michael T. Kleinman


Adjunct Professor, Center for Occupational and Environmental Health (COEH)
School of Medicine


M.S., Polytechnic Institute of Brooklyn, Biochemistry
Ph.D. (Environmental Health Sciences), New York University

Phone: (949) 824-4765
Fax: (949) 824-2070
Email: mtkleinm@uci.edu

University of California, Irvine
FRF 100
Mail Code: 1825
Irvine, CA 92697-182
Research Interests
Inhalation toxicology, oxidative stress and cardiopulmonary diseases.
Academic Distinctions
NY State Regents Scholarship; UCI Committee of 1000 Award
Research Abstract
My current research uses a well-understood model of cardiovascular disease, the apoE-/- mouse to study the role of inhaled contaminants including cigarette smoke, wildfire smoke, 'vaping' and ambient particles on the development of atherosclerosis and on changes in heart rate, heart rate variability, arrhythmias and blood pressure. Our findings have clearly indicated that the ultrafine fraction of ambient particulate matter which is highly enriched in organic constituents might be better able to promote atherosclerotic changes in arteries than larger ambient particles. To test hypotheses about the role of organic constituent we, in collaboration with colleagues at USC, developed a method to expose mice under field conditions to ambient particles from which the organic fraction was removed using a thermal denuding device in parallel with mice exposed to untreated ambient particles or purified air. These studies showed that removing the organics reduced the ability of the particles to generate free radicals and also to significantly reduce the rate of development of atherosclerotic plaque in the mice exposed to denuded particles compared to those exposed to un-denuded particles.
Short Biography
I have extensive experience in inhalation exposure studies and in the generation of test aerosols for inhalation studies and in the collection and analysis of contaminant aerosols and gases for organic constituents, including carbonyls and polycyclic organic compounds and for trace metals. My laboratory has an extensive history of performing whole body and nose-only exposure studies under field and laboratory conditions to examine effects of short term and chronic exposures to inhaled contaminants on immunological function and cardiopulmonary disease progression. Our findings have identified, in addition to adverse effects on cardiac physiology, significant evidence of tissue inflammation and oxidative stress including evidence of lipid peroxidation and free radical generation in arteries that correlate with development of atherosclerotic plaques. As part of the UCI Extension program I have, in the past, organized and conducted training programs in occupational and environmental health for firefighters, nurses and police. I co-chaired a National Research Council committee to evaluate our national preparedness for protecting US land and naval forces from chemical and biological weapons attacks, including efficacy of detection, PPE and decontamination systems. I have also served on EPA CASAC panels for PM, NO2 and CO, was a co-author of the WHO indoor air quality guidelines for CO (now in draft), and I am a member of the Scientific Review Pane for Toxic Substances which advises the California EPA and serve as a member of the Board of Scientific Counselors for the US EPA.
Publications
Kleinman MT, Mueller GR, Stevenson E, Alvarez R, Marchese AJ, Allen D. 2016. Emissions from oil and gas operations in the united states and their air quality implications. J Air Waste Manag Assoc 66:1165-1170.

125. Kleinman, M. T., et al. (2016). "Can reduced exposure to organic constituents of ambient particles prevent PM-induced acceleration of atherosclerosis and heart disease?" Toxicology Letters 259: S49-S50.


126. Kleinman, M. T., et al. (2016). "Emissions from oil and gas operations in the United States and their air quality implications." J Air Waste Manag Assoc 66(12): 1165-1170.

127. McCracken, A. N., et al. (2017). "Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation." Leukemia 31(3): 669-677

128. Kleinman, M. T. and J. G. Watson (2017). "Air quality measurements From rubber bands to tapping the rainbow." Journal of the Air & Waste Management Association 67(6): 635-636.

129. Kleinman, M. T., et al. (2017). "Air quality measurements-From rubber bands to tapping the rainbow." Journal of the Air & Waste Management Association 67(11): 1159-1168.

130. Ljubimova, J. Y., Kleinman, M.T.., et al. (2018). "Coarse particulate matter (PM2.5-10) in Los Angeles Basin air induces expression of inflammation and cancer biomarkers in rat brains." Scientific Reports 8: 5708 DOI:10.1038/s41598-018-23885-3.

131. Navarro, K. M., Kleinman, M.T., Mackay, C.E, Reinhardt, T.E., Balmes, J.R., Broyles, G.A., Ottmar, R.D., Naher, L.P., Domitrovitch, J.W. (2018) "Wildland firefighter smoke exposure and risk of lung cancer and cardiovascular disease mortality." Environ Res 173: 462-468.

132. OG Aztatzi-Aguilar, A Valdes-Arzate, Y Debray-Garcia, ES Caldero´n-Aranda, M Uribe-Ramirez, L Acosta-Saavedra, ME Gonsebatt, JA Maciel-Ruiz, P Petrosyan, V Mugica-Alvarez, MC Gutierrez-Ruiz, LE Gomez-Quiroz, A Osornio-Vargas, J Froines, MT Kleinman, and A De Vizcaya-Ruiz, (2018) "Exposure to ambient particulate matter induces oxidative stress in lung and aorta in a size- and time-dependent manner in rats", Toxicology Research and Application 2:1-15.

133. Araujo, J. E., Jorge, S., Santos, H.M., Chiechi, A.,Galstyan, A., Lodiero, C., Diniz, M., Kleinman, M.T., Ljubimova, J.Y., Capelo, J.L. (2019). "Proteomic changes driven by urban pollution suggest particulate matter as a deregulator of energy metabolism, mitochondrial activity, and oxidative pathways in the rat brain." Sci Total Environ 687: 839-848.

134. Capelo-Martinez, J. Ljubimova, J., Kleinman, M.T., et al., (2019) Proteomic changes driven by urban pollution suggest particulate matter as a deregulator of energy metabolism, mitochondrial activity, and oxidative pathways in the rat brain, Science of the Total Environment 687:839-848.

135. Perraud, V., Lawler, M., Malecha, K., Johnson, R., Herman, D., Staimer, N., Kleinman, M., Nizkorodov. and Smith, J. (2019). "Chemical characterization of nanoparticles and volatiles present in mainstream hookah smoke." Aerosol Science and Technology 53(9): 1023-1039.

136. Herman, D. A., Wingen, L.M., Johnson, R.M., Keebaugh, A.J., Renusch, S.R., Hasen, I., Ting, A.,Kleinman, M.T. (2020). "Seasonal effects of ambient PM2.5 on the cardiovascular system of hyperlipidemic mice." J Air Waste Manag Assoc 70(3): 307-323.

137. Independent Particulate Matter Review, P., Frey, H.C., Adams, P.J., Adgate, J.L., Allen, G.A., Balmes, J., Boyle, K., Chow, J.C., Dockery, D.W., Felton, H.D., Gordon, T., Harkema, J.R., Kinney, P., Kleinman, M.T., McConnell, R., Poirot, R.L., Sarnat, J.A., Sheppard, L., Turpin, B., Wyzga, R. (2020). "The Need for a Tighter Particulate-Matter Air-Quality Standard." N Engl J Med A 383(7): 680-683, DOI: 10.1056/NEJMsb2011009.

138. Ramanathan, G., Craver-Hoover B., Arechavala, R.J., Herman, D.A., Chen, J.H., Lai, H.Y., Renusch, S.R., Kleinman, M.T., Fleischman, A.G. (2020). "E-Cigarette Exposure Decreases Bone Marrow Hematopoietic Progenitor Cells." Cancers (Basel) 12(8).

139. Kemp, J. A., Keebaugh, A., Edson, J.A., Chow, D., Kleinman, M.T., Chew, Y.C., McCracken, A.N., Edinger, A.L., Kwon, Y.J. (2020). "Biocompatible Chemotherapy for Leukemia by Acid-Cleavable, PEGylated FTY720." Bioconjugate Chemistry 31(3): 673-684.

140. Altshuler, S. L., Zhang, Q., Kleinman, M.T., Garcia-Mendez, F., Moore, C.T.T., Hough, M.L., Stevenson, E.D., Chow, J.C., Jaffe, D.A., Watson, J.G. (2020). "Critical Review Discussion: Wildfire and prescribed burning impacts on air quality in the United States." J Air Waste Manag Assoc.

141. Kleinman, M. T., Arechavala, R.J., Herman, D., Shi, J., Hasen,I., Ting, A., Dai, W., Carreno, J., Chavez, J., Zhao, L. and Kloner, R.A. (2020). "E-cigarette or Vaping Product Use-Associated Lung Injury Produced in an Animal Model From Electronic Cigarette Vapor Exposure Without Tetrahydrocannabinol or Vitamin E Oil." J Am Heart Assoc: e017368.
 
140. Altshuler, S. L., Zhang, Q., Kleinman, M.T., Garcia-Mendez, F., Moore, C.T.T., Hough, M.L., Stevenson, E.D., Chow, J.C., Jaffe, D.A., Watson, J.G. (2020). "Critical Review Discussion: Wildfire and prescribed burning impacts on air quality in the United States." J Air Waste Manag Assoc.
 
139. Kemp, J. A., Keebaugh, A., Edson, J.A., Chow, D., Kleinman, M.T., Chew, Y.C., McCracken, A.N., Edinger, A.L., Kwon, Y.J. (2020). "Biocompatible Chemotherapy for Leukemia by Acid-Cleavable, PEGylated FTY720." Bioconjugate Chemistry 31(3): 673-684.
 
138. Ramanathan, G., Craver-Hoover B., Arechavala, R.J., Herman, D.A., Chen, J.H., Lai, H.Y., Renusch, S.R., Kleinman, M.T., Fleischman, A.G. (2020). "E-Cigarette Exposure Decreases Bone Marrow Hematopoietic Progenitor Cells." Cancers (Basel) 12(8).
 
137. Independent Particulate Matter Review, P., Frey, H.C., Adams, P.J., Adgate, J.L., Allen, G.A., Balmes, J., Boyle, K., Chow, J.C., Dockery, D.W., Felton, H.D., Gordon, T., Harkema, J.R., Kinney, P., Kleinman, M.T., McConnell, R., Poirot, R.L., Sarnat, J.A., Sheppard, L., Turpin, B., Wyzga, R. (2020). "The Need for a Tighter Particulate-Matter Air-Quality Standard." N Engl J Med A 383(7): 680-683, DOI: 10.1056/NEJMsb2011009.
 
136. Herman, D. A., Wingen, L.M., Johnson, R.M., Keebaugh, A.J., Renusch, S.R., Hasen, I., Ting, A.,Kleinman, M.T. (2020). "Seasonal effects of ambient PM2.5 on the cardiovascular system of hyperlipidemic mice." J Air Waste Manag Assoc 70(3): 307-323.
 
135. Perraud, V., Lawler, M., Malecha, K., Johnson, R., Herman, D., Staimer, N., Kleinman, M., Nizkorodov. and Smith, J. (2019). "Chemical characterization of nanoparticles and volatiles present in mainstream hookah smoke." Aerosol Science and Technology 53(9): 1023-1039.
 
134. Capelo-Martinez, J. Ljubimova, J., Kleinman, M.T., et al., (2019) Proteomic changes driven by urban pollution suggest particulate matter as a deregulator of energy metabolism, mitochondrial activity, and oxidative pathways in the rat brain, Science of the Total Environment 687:839-848.
 
Li, N., Harkema, J. R., Lewandowski, R. P., Wang, M., Bramble, L. A., Gookin, G. R., Ning, Z., Kleinman, M. T., Sioutas, C. and Nel, A. E. 2010 Ambient ultrafine particles provide a strong adjuvant effect in the secondary immune response: implication for traffic-related asthma flares. Am J Physiol Lung Cell Mol Physiol 299: L374-383.
 
Wu J, Edwards R, He XE, Liu Z, Kleinman M. 2010 Spatial analysis of bioavailable soil lead concentrations in Los Angeles, California. Environ Res 110(4): 309-317.
 
Simkhovich BZ, Kleinman MT, Kloner RA. 2009. Particulate air pollution and coronary heart disease. Current Opinion in Cardiology 24(6): 604-609.
 
Campbell A, Araujo JA, Li HH, Sioutas C, Kleinman M. 2009. Particulate Matter Induced Enhancement of Inflammatory Markers in the Brains of Apolipoprotein E Knockout Mice. Journal of Nanoscience and Nanotechnology 9(8): 5099-5104.
 
Kleinman MT, Araujo J, Nel A, Sioutas C, Campbell A, Cong PQ, Li A, Bondy SC, Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways, Toxicol Lett 178, 127-130, 2008.
 
Simkhovich BZ, Kleinman, MT, Kloner RA, Air pollution and cardiovascular injury: epidemiology, toxicology and mechanisms, J. Amer. Coll. Cardiol. 52:719-726, 2008.
 
Kleinman, MT, Sioutas, C, Froines, J, Fanning, E, Hamade, A, Meacher, D and Oldham, M., Inhalation of concentrated ambient particulate matter near a heavily trafficked road stimulates antigen-induced airway responses in mice: relevance of particle composition and size, Inhal. Toxicol., 19 Suppl 1: 117-126, 2007
 
Kleinman, M.T., Hyde, D., Bufalino, C., Basbaum, C., Bhalla, D.K. and Mautz, W.J Toxicity of Chemical Components of Fine Particles Inhaled by Aged Rats: Effects of Concentration. J. Air and Waste Management Assoc.53: 1080-1087, 2003.
 
Kleinman, M.T., Chang, M, Sioutas, C. and Cassee, F. Fine and coarse ambient particles suppress macrophage function. Toxicol. Letters 151-158, 2003.
 
Hall JV; Winer AM; Kleinman MT; Lurmann FW; Brajer V; Colome SD. Valuing the health benefits of clean air. Science, 1992 Feb 14, 255(5046):812-7.
 
Kleinman, M.T., Chang, M, Sioutas, C. and Cassee, F. 2002, Fine and coarse ambient particles suppress macrophage function. Toxicol. Letters 3:197-208.
 
Kleinman, M.T., Bufalino, C, Rasmussen, R. Hyde, D., Bhalla, D.K. and Mautz, W.J. Toxicity of chemical components of ambient fine particulate matter (PM2.5) inhaled by aged rats. J. Appl. Toxicol. 357-364, 2000.
 
Kleinman, M.T. Health Effects of Carbon Monoxide, in Environmental Toxicants, 2nd Edition M. Lippmann, ed. Van Nostrand Reinhold, publishers, New York, Jan. 2000.
 
Solomon, C., Christian, D. L., Chen, L. L., Welch, B. S., Kleinman, M. T., Dunham, E., Erle, D. J. and Balmes, J. R. Effect of serial-day exposure to nitrogen dioxide on airway and blood leukocytes and lymphocyte subsets. European Respiratory Journal 15:922-928, 2000.
 
Bondy, S.C., Ali, S.F. and Kleinman, M.T. Exposure of mice to tobacco smoke attenuates the toxic effects of methamphetamine on dopamine systems. Toxicol. Letters 118:43-46, 2000.
 
Chen Y, Douglass T, Jeffes EW, Xu Q, Williams CC, Arpajirakul N, Delgado C, Kleinman M, Sanchez R, Dan Q, Kim RC, Wepsic HT, Jadus MR. Living T9 glioma cells expressing membrane macrophage colony-stimulating factor produce immediate tumor destruction by polymorphonuclear leukocytes and macrophages via a "paraptosis"-induced pathway that promotes systemic immunity against intracranial T9 gliomas. Blood 100:1373-1380, 2002.
 
Jenkins, B.M., Mehlschau, J.J., Williams, R.B., Solomon, C., Balmes, J., Kleinman, M. And Smith, J. Rice Straw Smoke Generation System for Controlled Human Inhalation Exposures. Aerosol Sci. And Technol. 37: 437-454, 2003.
 
Opperhuizen, A., Buringh, E. And Kleinman, M.T. Compliance with PM standards in the European Union: A Netherlands case study. Environ. Management 53: 24-32, 2003
Grants
NIEHS 1R01ES027232-01, National Institute of Environmental Health Sciences09/01/2016-08/31/2021 Kleinman, Michael (PI) $1,050,041 Vapor and particulate phase smoke components and cardiovascular dysfunction $1,050,041 We will use state of the art chemical and physical analytical methods to determine how changes in waterpipe components and smoking patterns alter smoke chemistry as a function of particle size. Awe will use a combination of in-vitro and in vivo bioassays to test the toxicity of vapor and particle phase components and to determine the degree to which particle size and size-dependent composition variations affects toxicity. Role: PI 10%
CA-EPA 18RD012, California Air Resources Board01/01/2019 – 12/31/2022 Kleinman, Michael (UCI PI) White Paper to Review the Scientific Basis for a 1-hr PM2.5 Ambient Air Quality Standard?$50,000 Role: PI 20%
NHLBI F/HMRI 6085-18-01 09/14/2018-08/31/2023 Kloner R. HMRI PI; Kleinman UCI PI The effect of electronic cigarettes on young versus old normal hearts and pathologic hearts $859,500? The objectives of this study are to determine if chronic exposures in young, healthy animals increases health risks of smoking to a greater or lesser extent than does smoking in older animals. Role: PI UCI 7%
NHLBI Huntington 6075-18-01 09/18/2018-08/31/2023 Kloner R. HMRI PI; Kleinman UCI PI The effect of cigarette smoking and vaping on acute myocardial infarction $859,500? The objectives of this study are to determine if chronic exposures to vaping alters damage from MIs in animals with healthy and diseased cardiovascular systems.. Role: PI UCI 7%
Professional Societies
New York Academy of Sciences
American Chemical Society
American Association for Aerosol Research
Air and Waste Management Association
Society of Toxicology
Other Experience
Industrial hygiene and exposure assessment
Environmental Radiochemistry

Inhalation Toxicology


Graduate Programs
Environmental Toxicology

Environmental Health Sciences

Research Centers
UCI Comprehensive Cancer Center
Center for Occupational and Environmental Health
Last updated
10/21/2020