630 West 168th Street, College of Surgeons and Physicians Vanderbilt clinic, 11-215 Tel: (212) 305-3911 Fax: (212) 305-3229 At my most recent position at the Department of Radiation Oncology I was working at the scientific project jointly sponsored by DOE and NASA. Using global gene expression approaches such as Microarray and qPCR analysis we were studying dama ging effects of ionizing radiation on cell metabolism: differentiation, prolifer ation and gene expression. In our research program we used a wide spectrum of ex perimental models such as cell lines, peripheral blood cells and 3-dimensional t issue models reconstructed from the primary cells. We were the first who charact erized role of the transcription factor HNF4A in radiation response and identifi ed 38 novel biomarkers of ionizing radiation. We also designed and tested a real istic and tractable quantitative models for studies of individual tracks in 3-di mensional tissue model have provided insights into structural tissue remodeling caused by single HZE particles. Our main goal at this project was to provide spo nsors our expertise of possible health risks of ionizing radiation to the astron auts on the incoming space missions. Working at this project, I became an expert in detection and quantification of DNA damages and identification of genes that they have been caused. I have obtained my university degree in Biochemistry, which has prepared me for research at the interface of experimental and theoretical biology. My training a t the University included learning the existing techniques and design of new bio assays for separation of biomolecules. The School made me a highly trained profe ssional in the fields of protein purification, enzymology and protein chemistry. The classes were filled with an extensive analytical work, methods of quantitat ive analysis, enzyme kinetics, electrophoresis and chromatography. At least a ha lf of our lab work was dedicated to protein analysis. My PhD. work in the field of Molecular cloning was aimed at developing the simpl est model of NAD+-dependent catalysis. At this project, I established the proced ures for expression, purification and detection of proteins with different mutat ions in the active center. Moreover, I characterized these proteins by the metho ds of enzyme kinetics and compared their catalytic mechanisms. The results of th is work let us formulate the molecular mechanism of action of bacterial formate dehydrogenase. My postdoctoral included training in Medical genetics, Molecular Pharmacology, D ermatology and Radiation Oncology. I participated in the discovery of new signal ing molecules and molecular basis of lysosomal storage diseases. Working in Dr. Schwartzman's lab we described a new proinflammatory pathway in the cornea. Part icularly, we identified 12(R)-HETrE as a mediator of new proinflammatory pathway and CYP 4B1 as the enzymes that synthesizes 12(R)-HETrE from arachidonic acid. For the period less than 5 years, we followed 12(R)-HETrE signaling mechanism do wnstream to the step of transcriptional activation, cloned CYP 4B1 gene and isol ated promoter. Working at lysosomal storage diseases in St. Justine's hospital o ur group shed light at origination of galactosialidosis. We identified proteolyt ic degradation as the main reason of sialidase deficiency in the patient's cells and demonstrated that it was caused by a point mutation in its binding partner Cathepsin A. I anticipate that my new position will help me in my professional growth by shar pening my experimental and managerial skills. I have years of training in protei n biochemistry, molecular and cellular biology, pharmacology and radiation oncol ogy and familiarity with different experimental models such as primary cells, ce ll lines, peripheral blood cells and tissue samples. I am able to purify and cha racterize proteins from animal tissues and recombinant proteins expressed in COS cells, yeast and E.coli. I believe that my broad academic experience and years of training in protein chemistry make me perfect candidate for this role.
Thank you for your consideration,
Alexandre V. Mezentsev, PhD (845) 664-8532 mesentsev@yahoo.com