Research Microbiologist — Genetic and Molecular Toxicology

Vasily Dobrovolsky, Ph.D.
(870) 543-7121
NCTRResearch@fda.hhs.gov  

Back to NCTR Principal Investigator page

About  |  Publications  |  Lab Members

Background

Dr. Vasily Dobrovolsky received an M.S. in biotechnology in 1988 from the Moscow Institute of Physics and Technology and a Ph.D. in molecular biology in 1994 from the Institute of Bioorganic Chemistry at the Russian Academy of Sciences. Vasily joined NCTR in 1994 for postdoctoral training with Dr. Robert H. Heflich designing in vitro and in vivo models that detect mutation in endogenous and transgenic reporter genes; in 1998, he became an FDA Staff Fellow, and subsequently, a Research Microbiologist in NCTR’s Division of Genetic and Molecular Toxicology (DGMT). He oversees a group consisting of NCTR scientists, students and support personnel who are involved in research projects aimed at developing novel methodologies for basic and applied genetic toxicology.

Dr. Dobrovolsky has published over 60 book chapters and articles in peer-reviewed publications. He is a member of US Environmental Mutagenesis and Genomics Society; he has served as a Guest Editor to Special Issues of Environmental and Molecular Mutagenesis and Mutagenesis. He participated in working groups of the International Life Sciences Institute-Health and Environmental Sciences Institute, and International Workgroup on Genotoxicity Testing that dealt with integrating genetox assays into general toxicology protocols, quantitative analysis of genetic toxicology data and the Pig-a in vivo gene mutation assay. Awarded FDA Critical Path funding to develop a human Pig-a assay for use during clinical trials, 2008; awarded funding from the FDA Office of Women’s Health to study the Tk KO phenotype as a model of the autoimmune disease, lupus erythematosus.

Research Interests

Dr. Dobrovolsky is at the forefront of DGMT efforts in finding solutions to the complex problems faced by regulatory science in our modern technological society. Over the years he earned recognition for development and evaluation of tools for the assessment of safety and identification of potential hazards (i.e., carcinogens) among the products regulated by the U.S. Food and Drug Administration. His research interests involve the use of genetic engineering and various high throughput methodologies for designing in vitro and in vivo models capable of detecting and analyzing mutation. Dr. Dobrovolsky has used transgenic technology extensively for detecting hazards to the human genome. He designed a knockout mouse model for detecting mutation in the endogenous Tk locus. The model has been used to evaluate the mutagenicity of antiretroviral drugs. Anther model using a transgenic reporter, green fluorescent protein, has bridged the biology of mutation identification and high throughput scoring methodology using flow cytometry. The future use of targeted genome editing for therapeutic purposes (e.g., activating or deactivating endogenous genes or inserting transgenes using the Crispr/Cas9 system) warrants understanding potential negative side effects of the new therapy using various in vitro and in vivo models. Dr. Dobrovolsky was a co-inventor of the model for detecting mutation in the endogenous Pig-a gene and an enthusiastic promoter of its use in regulatory non clinical research. The Pig-a model uses flow cytometry for detecting cells having a mutant phenotype. The essential contributions of Dr. Dobrovolsky include extending the in vivo Pig-a model to species other than rodents and to in vitro cell cultures, as well as proving that the mutant phenotype measured by flow cytometry truly reflects mutation in the Pig-a gene. The rodent Pig-a model is at an advanced stage of acceptance for regulatory use. Yet, certain aspects of the Pig-a based model of mutation detection remain to be fully characterized. The model has translation potential as it is compatible with the detection of mutation in humans. Understanding the limitations and applicability of detecting Pig-a mutation in human patients for diagnostic and monitoring purposes will require further refinement in instrumental approaches and multiple testing the methodology in clinical trials. Recently, massive parallel sequencing, known as next generation sequencing or NGS, became an affordable and powerful tool in biomedical research. A group of scientists led by Dr. Dobrovolsky is exploring approaches for using NGS in regulatory genetic toxicology safety assessments. NGS complements the in vivo Pig-a gene model by making a quantitative leap in the ability to characterize mutations and build mutational spectra. Looking forward, NGS is poised to revolutionize the field of genetic toxicology by detecting mutation in any gene of any tissue of any species. In order to fully realize this potential, novel approaches in NGS sequencing chemistry and computational analyses of massive data arrays are developed by the group.

Professional Societies/National and International Groups

Environmental Mutagen and Genomics Society
Member
1996 – Present

International Life Sciences Institute (ILSI) Health And Environmental Sciences Institute (HESI) Workgroup To Develop The Pig-A Assay As An In Vivo Genotoxicity Test
Member
2014 – Present

International Workgroup On Genotoxicity Testing (IWGT) Committee On The Pig-A In Vivo Gene Mutation Assay
Member
2012 – 2014 

OECD Working Group On Developing An OECD TG For The Pig-A Assay
Member
2015 – Present

Select Publications

Publication titles are linked to text abstracts on PubMed.

Mutation Analysis With Random DNA Identifiers (MARDI) Catalogs Pig-A Mutations In Heterogeneous Pools Of CD48-Deficient T Cells Derived From DMBA-Treated Rats.
Revollo JR, Crabtree NM, Pearce MG, Pacheco-Martinez MM, Dobrovolsky VN.
Environ Mol Mutagen. 2016, 57(2):114-24.
 

The In Vivo Pig-A Assay: A Report Of The International Workshop On Genotoxicity Testing (IWGT) Workgroup.
Gollapudi BB, Lynch AM, Heflich RH, Dertinger SD, Dobrovolsky VN, Froetschl R, et al.
Mutat Res Genet Toxicol Environ Mutagen. 2015, 783:23-35.
 

CD48-Deficient T-Lymphocytes From DMBA-Treated Rats Have De Novo Mutations In The Endogenous Pig-A Gene.
Dobrovolsky VN, Revollo J, Pearce MG, Pacheco-Martinez MM, Lin H.
Environ Mol Mutagen. 2015, 56(8):674-83.
 

Confirmation Of Pig-A Mutation In Flow Cytometry-Identified CD48-Deficient T-Lymphocytes From F344 Rats.
Revollo J, Pearce MG, Petibone DM, Mittelstaedt RA, Dobrovolsky VN.
Mutagenesis. 2015, 30(3):315-24.
 

Monitoring Humans For Somatic Mutation In The Endogenous Pig-A Gene Using Red Blood Cells.
Dobrovolsky VN, Elespuru RK, Bigger CA, Robison TW, Heflich RH.
Environ Mol Mutagen. 2011; 52(9):784-94.
 

Evaluation Of Macaca mulatta As A Model For Genotoxicity Studies.
Dobrovolsky VN, Shaddock JG, Mittelstaedt RA, Manjanatha MG, Miura D, Uchikawa M, et al.
Mutat Res. 2009, 673(1):21-8.
 

Development Of An In Vivo Gene Mutation Assay Using The Endogenous Pig-A Gene: I. Flow Cytometric Detection Of CD59-Negative Peripheral Red Blood Cells And CD48-Negative Spleen T-Cells From The Rat.
Miura D, Dobrovolsky VN, Kasahara Y, Katsuura Y, Heflich RH.
Environ Mol Mutagen. 2008, 49(8):614-21.
 

On The Use Of The T-Rex Tetracycline-Inducible Gene Expression System In Vivo.
Dobrovolsky VN, Heflich RH.
Biotechnol Bioeng. 2007, 98(3):719-23.
 

Effect Of Arylformamidase (Kynurenine Formamidase) Gene Inactivation In Mice On Enzymatic Activity, Kynurenine Pathway Metabolites And Phenotype.
Dobrovolsky VN, Bowyer JF, Pabarcus MK, Heflich RH, Williams LD, Doerge DR, et al.
Biochim Biophys Acta. 2005, 1724(1-2):163-72.
 

Detection Of Mutation In Transgenic CHO Cells Using Green Fluorescent Protein As A Reporter.
Dobrovolsky VN, McGarrity LJ, Morris SM, Heflich RH.
Mutat Res. 2002, 518(1):55-64.
 

7,12-Dimethylbenz[A]Anthracene-Induced Mutation In The Tk Gene Of Tk(+/-) Mice: Automated Scoring Of Lymphocyte Clones Using A Fluorescent Viability Indicator.
Dobrovolsky VN, Shaddock JG, Heflich RH.
Environ Mol Mutagen. 2000, 36(4):283-91.
 

Tk+/- Mouse Model For Detecting In Vivo Mutation In An Endogenous, Autosomal Gene.
Dobrovolsky VN, Casciano DA, Heflich RH.
Mutat Res. 1999, 423(1-2):125-36.
 

Lab Members

Contact information for all lab members:
(870) 543-7121
NCTRResearch@fda.hhs.gov

Mason Pearce, MS
Microbiologist

Javier Revollo, Ph.D.
Staff fellow