Vladislav Dolgachev, Ph.D.
e-mail address: vdolgach@umich.edu

Mentor: Nicholas Lukacs , Ph.D. /Sem Phan , M.D., Ph.D.

Techniques Used:
Animal models of chronic airway diseases (in vivo experiments), Tissue culture (in vitro experiments), Protein and DNA electrophoresis, Western blots, RNA purification, Real time PCR, Thin layer chromatography, Spectrofluorimetry, Flow cytometry, Fluorescent microscopy, Determination of enzyme activity in vitro using radioactive and fluorescent substrates, Use of Radioisotopes


Research Description:

1) A Role of Stem Cell Factor (SCF) in Chronic Asthma, funded by the NIH, PI Nicholas W. Lukacs: We hypothesize that SCF production during allergic airway responses augments the progression of disease via eosinophil degranulation and production of profibrotic mediators leading to detrimental pathophysiology and airway remodeling. Blocking SCF-mediated activation within the airway using a monoclonal antibody indicates that this cytokine may represent a viable target for therapeutic intervention that could affect multiple aspects of allergen-induced immunopathology. The goal of project is to determine SCF signaling leading to eosinophil activation and specific profibrotic cytokine production. In addition, changes in airway physiology in normal and SCF deficient allergic mice would be assessed to elucidate the mechanism of SCF-induced eosinophil activation during disease development.

2) Bone marrow progenitor cells in lung fibrosis, funded by the Sandler Program for Asthma Research, PI Sem H. Phan, Co-PI Nicholas W. Lukacs. The goals of the project is to investigate a) whether fibroblast-like collagen producing cells involved in airway remodeling during chronic asthma may originate from bone marrow; b) whether previously observed beneficial effects of anti-SCF treatment on chronic asthma is due to the suppressed trafficking of bone marrow derived cells into the sites of airway remodeling.

Publications:

1. Dolgachev V, Ullenbruch MR, Lukacs NW, Phan SH. Role of stem cell factor and bone marrow derived fibroblasts in airway remodeling. The American Journal of Pathology. November 2008, Accepted for publication.

2. Dolgachev V, Berlin AA, Lukacs NW. Eosinophil activation of fibroblasts from chronic allergen-induced disease utilizes SCF for phenotypic changes. The American Journal of Pathology. 2008;172:68-76.

3. Dolgachev V, Thomas M, Berlin A, Lukacs NW. Stem cell factor-mediated activation pathways promote murine eosinophil CCL6 production and survival. Journal of Leukocyte Biology. 2007; 81(4):1111-1119.

4. Dolgachev V, Oberley LW, Huang TT, Kraniak JM, Tainsky MA, Hanada K, Separovic D. A role for manganese superoxide dismutase in apoptosis after photosensitization. Biochem Biophys Res Commun. 2005;332:411-4172.

5. Dolgachev V, Farooqui MS, Kulaeva OI, Tainsky MA, Nagy B, Hanada K, Separovic D. De novo ceramide accumulation due to inhibition of its conversion to complex sphingolipids in apoptotic photosensitized cells. J Biol Chem. 2004;279:23238-23249.

6. Dolgachev V, Nagy B, Taffe B, Hanada K, Separovic D. Reactive oxygen species generation is independent of de novo sphingolipids in apoptotic photosensitized cells. Exp Cell Res. 2003;288:425-436.

7. Molchan OV, Kim Iu V, Beliaeva TV, Dolgachev VA, Kovalev AE, Zinchenko VP, Volotovskii ID. The role of intracellular Ca(2+) pools in the regulation of protoplast volume. Effect of red light on the Ca(2+) mobilization in cytoplasm of Arabidopsis cells. Biofizika. 2001;46:642-646.

8. Dolgachev VA, Afanas'ev VN, Dolgacheva NN, Pechatnikov VA. Activation of poly(ADP-ribose)-polymerase inhibits apoptosis of thymocytes, caused by short-wave ultraviolet radiation. Biofizika. 2000;45:894-898.

9. Zinchenko VP, Mysiakin EB, Dolgachev VA, Dedkova EN, Safronova VG, Gapeev AB, Shebzukhov Iu V, Vaisbud M. Effect of structural analogs of platelet activating factor on the intracellular signal transduction in murine peritoneal neutrophils and macrophages of P388D1 line. Biofizika. 1997;42:1097-1105.

Honors and Awards:

1996: Russian Academy of Sciences, Puschchino’s Biological Center. Fellow Presentation Award.

1997: Russian Academy of Sciences, Puschchino’s Biological Center. Fellow Presentation Award.

2004: Wayne State University, The Eugene Applebaum College of Pharmacy and Health Sciences. Fellow Presentation Award.