Richard Albertini, M.D., Ph.D.
Research Professor Emeritus
Research Program: Genome Stability & Expression
VCC Membership Level: Member Scientist
Contact Information
Genetic Toxicology Lab
32 North Prospect Street
University of Vermont
Burlington, VT 05405
ph: (802) 656-8346
f: (802) 656-8333
Richard.Albertini@uvm.edu
Biography
Dr. Albertini received his M.D. from the University of Wisconsin Medical School in 1963 and his Ph.D. from the Department of Medical Genetics at the University of Wisconsin in 1972. Dr. Albertini joined the faculty of the UVM College of Medicine in 1974. In addition to his appointment in pathology, he is an adjunct member of the Department of Microbiology and Molecular Genetics.
Research
Dr. Albertini's research focuses on human somatic cell mutations. Somatic mutations arise in vivo in humans and can be measured and analyzed with precision. At the fundamental level, these mutations provide probes for investigating basic mutagenic mechanisms while, at the practical level, they provide biomarkers for assessing environmental health hazards. An important aspect of somatic mutations is their role in human diseases such as cancer.
The primary interest of Dr. Albertini's laboratory is somatic mutations that arise in vivo in human T-lymphocytes. They have developed a method for quantitating these events in the "reporter gene" hypoxanthine-guanine phosphoribosyltransferase (hprt) and have used it in a variety of human studies. One kind of study measures mutation induction in vivo in individuals exposed to environmental mutagens and carcinogens as a biomarker for assessing environmental cancer risks.
Mutant T-cells arising in vivo in humans can be isolated and characterized in vitro. Therefore, Dr. Albertini's laboratory has a major commitment in determining molecular mutational spectra. This has proved fruitful both for establishing basic mutagenic mechanisms and as a means for assessing the specificity of environmental mutagens/carcinogens.
Other studies of in vivo T-cell hprt mutations have revealed an unanticipated level of complexity. For example, in vivo mutations in T-lymphocytes arise preferentially in dividing as opposed to quiescent cells. Since most T-cells in vivo are in an arrested Go stage of the cell cycle, we have exploited this observation to detect immunologically relevant T-cells in individuals with autoimmune diseases. Such cells are more likely to be dividing, and thus more likely to have undergone mutation, than are quiescent cells.
Other studies have examined the role of development in somatic mutation. Lymphocyte mutations in the fetus, as determined in placental blood samples, are markedly different at the molecular level from those found in adults, indicating a fundamentally different mutational mechanism. This mechanism involves the differentiation of T-cells that results in rearrangement of their T-cell receptor (TcR) genes during thymic ontogeny. Rearrangement involves V(D)J recombinase which also induces illegitimate deletions in other genes, and may be an important fetal mutagenic mechanism in prenatal carcinogenesis.
Dr. Albertini's mutational studies in T-cells, therefore, include molecular analyses of TcR genes. Also, he is developing additional reporter genes. His laboratory has a concentrated effort in identifying individual susceptibiity to environmental mutagens and carcinogens as part of our overall interest in genetic predisposition to cancer. A major effort over the past two years has been the identification of T-lymphocytes with "mutator phenotypes" that arise in vivo in normal individuals.
Recent Publications
McDiarmid MA, Engelhardt SM, Dorsey C, Oliver M, Gucer P, Wilson PD, Kane R, Cermich A, Kaup B, Anderson D, Hoover D, Brown L, Albertini R, Gudi R, Squibb KS. (2008) Surveillance results of depleted uranium-exposed Gulf War I veterans: sixteen years of follow-up. J. Toxicol and Environmental Health Part A 72(1): 14-29
Swenberg JA, Fryar-Tita, E, Jeong YC, Boysen G, Starr T, Walker VE, Albertini RJ. (2008) Biomarkers in toxicology and risk assessment; informing critical dose-response relationships. Chem. Res. Toxicol. 21(1): 253-265
Berwick M, Albertini RJ. (2008) Biomarkers of mutation and DNA repair capacity. In Molecular Epidemiology of Chronic Diseases, Ed. Wild C, Vineis P, Garte S), John Wiley & Sons, Ltd, West Sussex, England. pp 127-139
Albertini MR, Macklin MD, Zuleger CL, Newton MA, Judice SA, Albertini RJ. (2008) Clonal expansions of 6-thioguanine resistant T-lymphocytes in the blood and tumor of melanoma patients. Environ. Mol. Mutagen. 49(9): 676-687
Albertini RJ, Sram RJ, Vacek PM, Lynch J, Nicklas JA, McDonald J, Swenberg JA (2007) Molecular epidemiological studies in 1,3-butadiene exposed Czech workers: female-male comparisons Chem. Bio. Interact. 166(1-3): 63-77
Sram RJ, Rossner P, Beskid O, Bavorova H., Ocadlikova D, Solansky I, Albertini RJ (2007) Chromosomal aberration frequencies determined by conventional methods: Parallel increases over time in the region of a petrochemical industry and throughout the Czech Republic. Chem. Bio. Interact. 166(1-3): 239-244
Himmelstein MW, Baan RA, Albertini RJ, Bird MG, Lewis JR (2007) Forward: International Symposium on the Evaluation of Butadiene and Chloroprene Health Risks. Chem. Bio. Interact. 166(1-3): 1-9
Albertini RJ, Sweeny LM (2007) Propylene Oxide: genotoxiticy profile of a rodent nasal carcinogen. Critical Reviews in Toxicology. 37: 1-32
McDiarmid MA, Engelhardt SM, Oliver M, Gucer P, Wilson PD, Kane R, Cernich A, Kaup B, Anderson L, Hoover D, Brown L, Albertini R, Gudi R, Jacobson-Kram D, Squibb KS (2007) Health surveillance of Gulf War I veterans exposed to depleted uranium: Updating the cohort. Health Physics 93 (1); 60-73
Bendre, SV, Shaddock, JG, Dobrovolsky, VN, Albertini, RJ, Heflich, RH (2007) Effect of chronic azathioprine treatment on germ-line transmission of Hprt mutation in mice. Environ. Mol. Mutagen. 48(9): 744-753
Albertini RJ, Bird MG, Doerrer NG, Needham LL, Robison SH, Zenick H (2006) Common principles for the use of biomonitoring data in exposure and human helath risk assessment Environ Health Persp. 114(11): 1755-1762
McDiarmid MA, Engelhardt SM, Oliver M, Gucer P, Wilson PD, Kane R, Kabat M, Kaup B, Anderson L, Hoover D, Brown L, Albertini RJ, Gudi R, Jacobson-Kram D, Thorne CD Squibb KS (2006) Biological Monitoring and Surveillance Results of Gulf War I Veterans Exposed to Depleted Uranium. Int Arch Occup Environ Health. 79(1): 11-21
Allegretta M, Ardell SK, Sullivan LM, Jacobson S, Mortreux F, Wattel E, Albertini RJ. HPRT mutations, TCR gene rearrangements, and HTLV-1 integration sites define in vivo T-cell clonal lineages. Environ Mol Mutagen 2005 Mar-Apr 45(2-3), 326-37.
O'Neill P, Nicklas J, Hirsch B, Jostes R, Hunter T, Sullivan L, Albertini R. In vitro studies of the genotoxicity of ionizing radiation in human G(0) T lymphocytes. Environ Mol Mutagen 2005 May 10.
Other Key Publications
Toraason M, Albertini R, Bayard S, Bigbee W, Blair A, Boffetta P, Bonassi S, Chanock S, Christiani D, Eastmond D, Hanash S, Henry C, Kadlubar F, Mirer F, Nebert D, Rapport S, Rest K, Rothman N, Ruder A, Savage R, Schulte P, Siemiatycki J, Shields P, Smith M, Tolbert P, Vermeulen R, Vineis P, Wacholder S, Ward E, Waters M, Weston A. Applying new biotechnologies to the study of occupational cancer--a workshop summary. Environ Health Perspect 2004 Mar 112(4), 413-6.
Kirman CR, Sweeney LM, Teta MJ, Sielken RL, Valdez-Flores C, Albertini RJ, Gargas ML. Addressing nonlinearity in the exposure-response relationship for a genotoxic carcinogen: cancer potency estimates for ethylene oxide. Risk Anal 2004 Oct 24(5), 1165-83.
Albertini RJ. Mechanistic insights from biomarker studies: somatic mutations and rodent/human comparisons following exposure to a potential carcinogen. IARC Sci Publ 2004 157), 153-77.
McDiarmid MA, Engelhardt S, Oliver M, Gucer P, Wilson PD, Kane R, Kabat M, Kaup B, Anderson L, Hoover D, Brown L, Handwerger B, Albertini RJ, Jacobson-Kram D, Thorne CD, Squibb KS. Health effects of depleted uranium on exposed Gulf War veterans: a 10-year follow-up. J Toxicol Environ Health A. 2004 Feb 27;67(4):277-96.
Albertini R, Clewell H, Himmelstein MW, Morinello E, Olin S, Preston J, Scarano L, Smith MT, Swenberg J, Tice R, Travis C. The use of non-tumor data in cancer risk assessment: reflections on butadiene, vinyl chloride, and benzene. Regul Toxicol Pharmacol 2003 Feb 37(1), 105-32.
McDiarmid MA, Engelhardt S, Oliver M, Gucer P, Wilson D, Kane R, Kabat M, Kaup B, Anderson L, Hoover D, Brown L, Handwerger B, Albertini RJ, Jacobson-Kram D, Thorne C, Squibb K. Health effects of depleted uranium on exposed Gulf War veterans: A ten-year follow-up. J Toxicol Environ Health 2003.
Albertini RJ, Sram RJ, Vacek PM, Lynch J, Nicklas JA, van Sittert NJ, Boogaard PJ, Henderson RF, Swenberg JA, Tates AD, Ward JB Jr, Wright M, Ammenheuser MM, Binkova B, Blackwell W, de Zwart FA, Krako D, Krone J, Megens H, Musilova P, Rajska G, Ranasinghe A, Rosenblatt JI, Rossner P, Rubes J, Sullivan L, Upton P, Zwinderman AH. Biomarkers in Czech workers exposed to 1,3-butadiene: a transitional epidemiologic study. Res Rep Health Eff Inst. 2003 Jun;(116):1-141; discussion 143-62.
Albertini RJ. Correspondence re: Czene et al., Analysis of DNA and hemoglobin adducts and sister chromatid exchanges in a human population occupationally exposed to propylene oxide: a pilot study. Cancer Epidemiol. Biomark. Prev., 11: 315-318, 2002. Cancer Epidemiol Biomarkers Prev. 2003 Apr;12(4):388; author reply 388-9.
Perera F, Hemminki K, Jedrychowski W, Whyatt R, Campbell U, Hsu Y, Santella R, Albertini R, O'Neill JP. In utero DNA damage from environmental pollution is associated with somatic gene mutation in newborns. Cancer Epidemiol Biomarkers Prev 2002 Oct 11(10 Pt 1), 1134-7.
Leoni V, Albertini R, Passi A, Abuja PM, Borroni P, D'Eril GM, De Luca G. Glucose accelerates copper- and ceruloplasmin-induced oxidation of low-density lipoprotein and whole serum. Free Radic Res 2002 May 36(5), 521-9.
Ballinger SW, Judice SA, Nicklas JA, Albertini RJ, O'Neill JP. DNA sequence analysis of interlocus recombination between the human T-cell receptor gamma variable (GV) and beta diversity-joining (BD/BJ) sequences on chromosome 7 (inversion 7). Environ Mol Mutagen. 2002;40(2):85-92.
Finette BA, Homans AC, Rivers J, Messier T, Albertini RJ. Accumulation of somatic mutations in proliferating T cell clones from children treated for leukemia. Leukemia 2001 Dec 15(12), 1898-905.
Albertini RJ. Validated biomarker responses influence medical surveillance of individuals exposed to genotoxic agents. Radiat Prot Dosimetry. 2001;97(1):47-54. Review.
Albertini RJ. HPRT mutations in humans: biomarkers for mechanistic studies. Mutat. Res. 2001 Oct; 489(1): 1-16.
Albertini RJ, Sram RJ, Vacek PM, Lynch J, Wright M, Nicklas JA, Boogaard PJ, Henderson RF, Swenberg JA, Tates AD, Ward JB Jr. Biomarkers for assessing occupational exposures to 1,3-butadiene. Chem. Biol. Interact. 2001 Jun 1; 135-136: 429-453.
Albertini RJ, Ardell SK, Judice SA, Jacobson S, Allegretta M. Hypoxanthine-guanine phosphoribosyltransferase reporter gene mutation for analysis of in vivo clonal amplification in patients with HTLV type 1-associated Myelopathy/Tropical spastic paraparesis. AIDS Res. Hum. Retroviruses 2000 Nov 1; 16(16): 1747-1752.
Albertini RJ, Anderson D, Douglas GR, Hagmar L, Hemminki K, Merlo F, Natarajan AT, Norppa H, Shuker DE, Tice R, Waters MD, Aitio A. IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety. Mutat Res 2000 Aug 463(2), 111-72.
Finette BA, Homans AC, Albertini RJ Emergence of genetic instability in children treated for leukemia. Science 2000 Apr 21; 288(5465): 514-517.
