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Elena Paskaleva

Elena Paskaleva

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About Me

I got a Master's degree in Molecular and Cell Biology from the Faculty of Biology at the Sofia University working on in vitro expression system for Calcitonin - a small peptide hormone which protects against bone loss. My Ph.D. project studied the genetic basis for the inter-individual expression levels of the enzymes from the CYP3A family with a view of developing personalized medications. Otherwise put, I tried to figure out why one and the same pill has a different effect on different patients by looking at the genetic makeup of the patients, as well as the epigenetic modifications of their liver enzymes. Once in the States, I worked in the field of molecular virology and AIDS research. One topic of my work was to study how the practically impermeable blood-brain barrier (BBB) allows HIV to penetrate into the brain and cause the irreversible HIV-associated dementia (HAD). Another line of research was HIV entry inhibitors of natural origin. Once in the body, HIV integrates with the human DNA - and cannot be removed, and remains there forever. Most all of the current AIDS medications are reverse transcription inhibitors, acting after the infection has already set in. We decided to look for potential therapeutics that prevent the virus from infecting in a first place - either to stop the cell-to-cell spread in already exposed patients, or as part of pre-exposure prophylaxis (PrEP). Also, knowing that the currently available drugs often have considerable side effects, we focused the work on identifying treatments of natural origin that were likely to be more agreeable with the metabolism of the patients. We fractionated and screened a lot of plants, which have been known to alleviate symptoms of viral infections. We identified a panel of antiviral compounds, specifically active against HIV.

Former Education

Ph. D. (1999-2003) University of Manchester, England, School of Medicine, Dentistry, and Pharmacy

M.B.A. (1996-1998) University of National and World Economy, Sofia, Bulgaria

M.S. (1996) Sofia University St. Kliment Ohridski, Bulgaria

Research

My research at the Dordick Group targets microbial pathogens that are hard to kill. Bacterial infections are commonly treated with antibiotics. However, some of the most dangerous and persistent pathogens - such as Bacillus anthracis and Clostridium sp. – transform rapidly into dormant spores, when challenged. The spores don't have metabolism, so they cannot be treated with antibiotics. They are extremely well protected by multiple coat layers, which makes them practically impermeable to all but the harshest decontamination procedures. We are exploring the idea to use lytic and germination enzymes, produced in nature by the same bacteria at different stages of their life cycle, to coerce them out of dormancy. The germinating vegetative body then becomes vulnerable and can be killed. Our target organism is Bacillus anthracis, the etiological agent of anthrax – and notorious bioterrorist weapon. We are also expanding the work to the four major Clostridium species – C. difficile, C. perfringens, C. tetani, and C. botulinum, which are responsible for hospital-acquired infections, food poisoning from canned products, and gas gangrene at the site of open wounds.

elena research

Publications

Paskaleva EE, Xue J, Lee DY, Shekhtman A, Canki M. Palmitic acid analogs exhibit nanomolar binding affinity for the HIV-1 CD4 receptor and nanomolar inhibition of gp120-to-CD4 fusion. PLoS One. 2010 Aug 13;5(8):e12168. PubMed PMID: 20730055; PubMed Central PMCID: PMC2921400

Lee DY, Lin X, Paskaleva EE, Liu Y, Puttamadappa SS, Thornber C, Drake JR, Habulin M, Shekhtman A, Canki M. Palmitic Acid Is a Novel CD4 Fusion Inhibitor That Blocks HIV Entry and Infection. AIDS Res Hum Retroviruses. 2009 Dec;25(12):1231-41. PubMed PMID: 20001317; PubMed Central PMCID: PMC2828184.

Cismasiu VB, Duque J, Paskaleva E, Califano D, Ghanta S, Young HA, Avram D. BCL11B enhances TCR/CD28-triggered NF-kappaB activation through up-regulation of Cot kinase gene expression in T-lymphocytes. Biochem J. 2009 Jan 15;417(2):457-66. PubMed PMID: 18831712; PubMed Central PMCID: PMC2639648.

Cismasiu VB, Paskaleva E, Suman Daya S, Canki M, Duus K, Avram D. BCL11B is a general transcriptional repressor of the HIV-1 long terminal repeat in T lymphocytes through recruitment of the NuRD complex. Virology. 2008 Oct 25; 380(2):173-81. Epub 2008 Sep 2. PubMed PMID: 18768194; PubMed Central PMCID: PMC2637995.

Paskaleva EE, Lin X, Duus K, McSharry JJ, Veille JC, Thornber C, Liu Y, Lee DY, Canki M. Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase. Virol J. 2008 Jan 15;5:8. PubMed PMID: 18197976; PubMed Central PMCID: PMC2267448.

Paskaleva EE, Lin X, Li W, Cotter R, Klein MT, Roberge E, Yu EK, Clark B, Veille JC, Liu Y, Lee DY, Canki M. Inhibition of highly productive HIV-1 infection in T cells, primary human macrophages, microglia, and astrocytes by Sargassum fusiforme. AIDS Res Ther. 2006 May 25;3:15. PubMed PMID: 16725040; PubMed Central PMCID: PMC1481599.

Hobbies and Activities

Reluctant movie buff.

Enthusiastic sci-fi fan - Blake's 7; James Blish ("The Seedling Stars"), James White (the "Sector General" books), Robert Sheckley (check out "Ghost V", but any other will do too), Asimov goes without saying.

Compulsive reader - Terry Pratchett and Lois McMaster Bujold come to mind, but would read anything. Easily can get engrossed in the labels on back of cereal boxes during breakfast.

Collector. I collect books (see above) and quotes. As in

"If we knew what it was we were doing, it would not be called research."; Albert Einstein

"Another response of the wizards, when faced with a new and unique situation, was to look through their libraries to see if it had ever happened before. This was, Lord Vetinari reflected, a good survival trait. It meant that in times of danger you spent the day sitting very quietly in a building with very thick walls." --Terry Pratchett, "The Last Hero"