The Robert F. Furchgott Society
2008 Robert F. Furchgott Award Recipients
The Robert F. Furchgott Fellowship Award
Awardee: Ghazanfar Qureshi, MD
Department of Medicine
Dr. Qureshi’s studies, conducted under the direction of Drs. Jason Lazar and Louis Salciccioli, examined the mechanisms and significance of increased arterial stiffness. Arterial stiffness, a biophysical property of the arterial system that is predictive of increased cardiovascular risk, is correlated with left ventricular hypertrophy and the presence and severity of coronary artery disease. Dr. Qureshi investigated the relationship between atherosclerosis and arterial stiffness and found stiffness to vary among patients with little atherosclerosis but to be uniformly increased in those with more marked atherosclerotic disease. These data suggested multiple mechanisms contributing to arterial stiffness. With further study, he found that the use of beta blockers, a commonly prescribed class of medications for patients with heart disease, is associated with higher arterial stiffness. This may account for the decreased efficacy shown for this drug class in primary prevention trials. Dr. Qureshi proposed a new measure of arterial stiffness, derived from the dynamic relationship between systolic and diastolic blood pressures called “self-measured arterial stiffness index”. The index, which uses self-measured blood pressure recordings, increased with cardiovascular risk factors and was positively correlated with direct measures of arterial stiffness. In two additional studies, Dr Qureshi found that arterial stiffness is higher in women with systemic lupus erythematosus, and that bone demineralization is associated with higher arterial stiffness, independent of atherosclerosis. These latter studies suggest that inflammation and vascular calcification contribute to the development of arterial stiffness.
The Robert F. Furchgott Fellowship Award
Awardee: Vera Pisareva, PhD
Department of Molecular Biology and Genetics
Dr. Pisareva’s studies, conducted in the laboratory of Dr. Tatyana Pestova, focused on the mechanism of translation initiation on eukaryotic mRNAs containing structured 5'-untranslated regions (UTR). Most eukaryotic mRNAs possess relatively short unstructured 5’- UTRs. Initiation on unstructured 5'-UTRs is described in terms of the ribosomal scanning model, in which 43S preinitiation ribosomal complexes first attach to the capped 5’-proximal region of mRNA and then scan along the 5’UTR to the initiation codon where they form 48S initiation complexes. Attachment of 43S complexes is mediated by initiation factors eIF4F, eIF4A and eIF4B, which cooperatively unwind the cap-proximal region of mRNA. In addition to this role, eIF4F, eIF4A and eIF4B also assist 43S complexes during scanning. Dr. Pisareva's novel research demonstrated that these canonical initiation factors are not sufficient for efficient initiation on mRNAs with structured 5’-UTRs. She identified an additional factor, the DExH-box protein DHX29, that is required for this process. DHX29 binds 40S subunits and efficiently hydrolyzes ATP, GTP, UTP and CTP. NTP hydrolysis by DHX29 is stimulated by 43S complexes, and is required for DHX29’s activity in promoting 48S complex formation.
2007 Robert F. Furchgott Award Recipients
The Robert F. Furchgott Award for Excellence in Research
Awardee: Paul Stephen Rava., PhD
Molecular & Cellular Biology Programs, School of Graduate Studies
Dr. Paul Stephen Rava, the recipient of the 2007 Robert F. Furchgott Award for Excellence in Research is currently in the fourth year of the College of Medicine and is one of the finest students to be trained in Downstate’s School of Graduate Studies. Paul epitomizes the research excellence that is expected of the awardee of this prestigious prize. Dr. Rava’s thesis is titled “The Evolution of Microsomal Triglyceride Transfer Protein and its Role during the Assembly of ApoB-lipoptroteins.” As part of his research conducted in the laboratory of Dr. Xian-Cheng Jiang, Dr. Rava designed a new fluorescence-based assay for measuring cholesterol ester and the phospholipid transfer activity of microsomal triglyceride transfer protein (MTP) a key enzyme in the biogenesis of apoB-lipoproteins. He used this and other assays to compare MTPs from different organisms. Dr. Rava demonstrated that the phopholipid transfer activity of MTP is evolutionarily conserved, and that its more recently acquired triacylgycerol transfer activity, found in vertebrates, resides in a particular domain of the enzyme. His research results have been published in eight peer-reviewed journal articles including four first-authored papers.
The Robert F. Furchgott Fellowship Award
Awardee: Andrey Pisarev, Ph.D. Research Fellow
Department of Microbiology & Immunology
Dr. Andrey Pisarev is the recipient of the 2007 Robert F. Furchgott Fellowship Award. Dr. Pisarev’s studies, conducted in the laboratory of Dr. Tatyana Pestova, were focused on determining the mechanism of eukaryotic ribosomal complex recycling. After termination, mRNA and P site deacylated tRNA remain associated with ribosomes in post-termination complexes (post-TCs), which therefore have to be recycled by splitting them into ribosomal subunits and dissociating mRNA and deacylated tRNA. Recycling of bacterial post-TCs requires elongation factor EF-G and a ribosome recycling factor RRF. Eukaryotes do not encode a RRF homologue and their mechanism of ribosomal recycling is unknown. Dr. Pisarev investigated eukaryotic recycling using post-TCs assembled in vitro on a model mRNA encoding a tetrapeptide followed by a UAA stop codon. He reported that initiation factors eIF3, eIF1, eIF1A and eIF3’s loosely associated eIF3j subunit can promote recycling of eukaryotic post-TCs. eIF3 is the principal factor that promotes splitting of post-termination ribosomes into 60S subunits and tRNA- and mRNA-bound 40S subunits. Its activity is enhanced by eIF3j, eIF1 and eIF1A. eIF1 also mediates release of P-site deacylated tRNA, whereas eIF3j ensures subsequent mRNA dissociation.
The Robert F. Furchgott Fellowship Award
Awardee: Anett Unbehaun, M.D., Ph.D. Research Fellow
Department of Microbiology & Immunology
Dr. Anett Unbehaun is the recipient of the 2007 Robert F. Furchgott Fellowship Award. Dr. Unbehaun studies protein synthesis in eukaryotic cells in the laboratory of Dr. Tatyana Pestova. Her work focuses on the molecular mechanism by which eukaryotic initiation factor (eIF) 5B promotes joining of the ribosomal subunits at the end of the initiation process. Dr. Unbehaun determined the position of eIF5B on the 80S ribosome and described the first eIF5B/ 80S ribosome model. The data indicate that eIF5B is located in the intersubunit cleft of the ribosome. eIF5B occupies a large surface on the small subunit and is located in close proximity to the GTPase associated center and the peptidyltransferase center of the large subunit. The eIF5B/ 80S ribosome model also indicates that eIF5B induces substantial conformational changes in both ribosomal subunits.
2006 Robert F. Furchgott Award Recipients
The Robert F. Furchgott Award for Excellence in Research
Awardee: Richard Pomerantz, Ph.D.
Molecular & Cellular Biology Program,
School of Graduate Studies
Dr. Richard Pomerantz is the recipient of the 2006 Robert F. Furchgott Award for Excellence in Research. Dr. Pomerantz's studies, conducted in the laboratory of Dr. William McAllister, explored the potential applications of T7 RNAP, a polymerase in bacteriophage as a tightly regulated molecular motor in nanotechnology. He investigated the mechanism by which T7 RNAP selects for correct nucleotide substrates during transcription. T7 RNAP converts the chemical energy stored in nucleotide triphosphates (NTPs), like ATP, into the mechanical work of transcription. Previous studies had shown that T7 RNAP can exert forces up to 30 piconewtons as it moves along the DNA while copying the information in the DNA template into RNA. Dr. Pomerantz demonstrated that the forward motion of T7 RNAP is dependent on the availability of the next incoming (correct) NTP that is encoded by the template strand of the DNA. Dr. Pomerantz received his Ph.D. in Molecular and Cellular Biology from SUNY Downstate Medical Center in May 2006.
