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The Robert F. Furchgott Society2009 Robert F. Furchgott Award RecipientsRobert F. Furchgott Award for Excellence in ResearchAwardee: Melissa James Dr. Melissa James is the recipient of the 2009 Robert F. Furchgott Award for Excellence in Research. Dr. James' thesis research, conducted in the laboratory of Dr. Stacy Blain, focused on the regulation of the oncogene cyclin D-cdk4 by the tumor suppressor p27. p27 is a potent inhibitor of cell cycle progression and detection of low p27 levels correlates with a poor prognosis in many cancers. Her studies demonstrated that p27 can be either a cyclin D-cdk4 bound, inhibitor or a bound, activator, depending on the growth state of the cell. In proliferating cells, p27 is tyrosine phosphorylated in its 3-10 helix and this allows it to bind to cyclin D-cdk4 without causing inhibition. When cells are arrested by contact, p27 is no longer tyrosine phosphorylated and now binds to the cyclin D-cdk4 complex in an inhibitory conformation. Tyrosine phosphorylation in the 3-10 helix appears to prevent an interaction between p27 and the cdk subunit, permitting ATP access to cdk4's activity site. Her work was among the first to demonstrate that p27 could be tyrosine phosphorylated and more importantly finally answered the long-standing question in the cell cycle field about how p27 could transition from activator to inhibitor, and vice versa. These studies were the first to demonstrate that tyrosine phosphorylation affected p27's ability to inhibit cyclin D-cdk4 and has been published in two peer reviewed journal articles. This work was also cited by Faculty of 1000 Biology for its important contribution to the field. Robert F. Furchgott Medical Student Award for Excellence in ResearchAwardee: Jonathan Silverberg 
Jonathan Silverberg, MD, PhD, MPH candidate ('09) is the recipient of the 2009 Robert F. Furchgott Medical Student Award. Jonathan received this award for two translational studies of regulation of human allergic responses, conducted under the mentorship of Drs. Rauno Joks, Department of Medicine, Tamar-Smith Norowitz, Department of Pediatrics, and Helen G. Durkin, Department of Pathology. With Drs. Joks and Durkin, Jonathan discovered that minocycline, a new anti-allergic drug invented at SUNY Downstate, suppresses P38 MAP kinase phosphorylation, an upstream molecular event required for suppression of Th2 cytokine and IgE responses. With Drs. Smith-Norowitz, Joks and Durkin, he discovered a new T cell subpopulation (CD8+CD60+CD45RO+TCR alpha/beta+) whose 5 cytokines are absolutely required, along with IL-4 produced by CD4+ T cells, for induction of human memory IgE responses. These discoveries provide new targets for anti-allergic drugs. Jonathan received his PhD degree in Neuroscience in 2006 under the mentorship of Dr. Durkin and Drs. Mark Stewart and Vahe Amassian, Department of Physiology-Pharmacology, for which he was awarded the 2009 Chancellor's Award for Student Excellence. Robert F. Furchgott Resident Award for Excellence in ResearchKelley A. Sookraj, MD 
Dr. Kelley A. Sookraj's research was conducted in the laboratories of Drs. Wilbur B. Bowne, Josef Michl, and Matthew R. Pincus. Dr. Sookraj's studies focused on oncogenesis, oncoprotein structure, mitogenic signal transduction, and design of anticancer agents. This laboratories earlier work utilized a computer-based molecular modeling approach to identify various sequences from the murine double minute binding domain of p53, known as MDM-2, that were shown to possess anticancer activity. Two such synthesized peptides, designated PNC-27 and PNC-28, demonstrated potent anticancer activity against a rodent metastatic pancreatic and selected human cancer cell lines: an effect not observed among their untransformed cellular counterparts. The observed cytotoxic effect of these p53-derived peptides was later found to occur by the mechanism of necrosis rather than apoptosis in both wild-type p53 and p53 null cancer cell lines providing evidence for a p53-independent anticancer mechanism. Current studies reveal that these amphipathic, PNC peptides target the over-expressed MDM-2 oncoprotein, unique to selected cancer cell membranes, leading to trans-membrane pore formation, membranolysis, and cancer cell death by necrosis. The effect of these novel anticancer peptides, upon further investigation, suggests that these PNC peptides may potentially serve an important role in the future treatment of certain cancers. Robert F. Furchgott Fellowship Award for Excellence in Basic Science ResearchXiaoyue Pan, PhD 
Dr. Xiaoyue Pan, in the laboratory of Dr. M. Mahmood Hussain, explored mechanisms responsible for diurnal and food-entrained regulation of nutrient absorption by the gut and changes in plasma lipids. She identified that transcriptional regulation of microsomal triglyceride transfer protein (MTP) correlates with changes in plasma triglycerides in rodents kept in 12 h light/dark cycle and fed ad libitum. To understand how light and food control MTP, Dr. Pan used cells that exhibit cyclic expression of MTP after exposure to high serum concentrations. Using siRNA, she elucidated that Clock transcription factor regulates SHP, a negative regulator of MTP transcription, and controls MTP expression. In addition, she investigated the role of clock genes, which are critical for circadian regulations, in the control of intestinal function. She showed that expression of intestinal protein, carbohydrate, and lipid transporters show diurnal variations. Dr. Pan also demonstrated that transcription factors involved in circadian rhythms are important for both light and food-entrainment of intestinal transporters using dominant negative Clock mutant mice. These studies indicate that both light and food entrainment mechanisms might utilize the same or similar set of clock genes that show cyclic expression to regulate metabolism. Therefore, disruptions in circadian regulations might contribute to hyperlipidemia and hyperglycemia. Understanding molecular and biological mechanisms regulating daily variations in plasma lipids may provide new perceptions about the pathobiology of common metabolic disorders. « Back to Top2008 Robert F. Furchgott Award RecipientsThe Robert F. Furchgott Award for Excellence in ResearchAwardee: Daisy Lin, PhD I studied the role of small untranslatable RNAs called BC (brain specific) RNAs in the regulation of gene expression. BC1 and BC200 RNAs are highly abundant in the brains of rodents and humans, respectively. BC RNAs localization, in dendrites of neurons where local postsynaptic protein synthesis takes place, make them candidates for the regulation of input specific synaptic plasticity. Previously, BC1 RNA has been shown to inhibit protein synthesis at the level of translation. In my thesis, I examined the underlying functional mechanisms between BC1 RNA and its two binding factors, eukaryotic initiation factors 4A (eIF4A) and poly (A) binding protein (PABP). Biochemically, BC1 RNA binding to either eIF4A or PABP is of high affinity. eIF4A is an RNA helicase that hydrolyzes ATP to unwind the mRNA secondary structure during translation initiation. I showed that eIF4A-dependent helicase activity is uncoupled from its ATPase activity by both BC RNAs. Helicase stimulator eIF4B and adenosine nucleotides are shown to be involved in the modulation of the BC1-eIF4A interaction. In HEK293 cells, I showed that BC1 RNA inhibits translation of 5' secondary structure containing chloramphenicol acetyltransferase (CAT) mRNA with or without a poly (A) tail. My data suggest that the mechanism by which dendritic BC1 RNA inhibits protein synthesis at the level of translation is by targeting the catalytic activity of eIF4A and interacting specifically with PABP, My work provide new insight in understanding the mechanism of local translation control by small neuronal RNAs. The Robert F. Furchgott Fellowship AwardAwardee: Ghazanfar Qureshi, MD 
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 AwardAwardee: Vera Pisareva, PhD 
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. « Back to Top2007 Robert F. Furchgott Award RecipientsThe Robert F. Furchgott Award for Excellence in ResearchAwardee: Paul Stephen Rava., PhD 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. M. Mahmood Hussain, 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 AwardAwardee: Andrey Pisarev, Ph.D. Research Fellow 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 AwardAwardee: Anett Unbehaun, M.D., Ph.D. Research Fellow 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. « Back to Top2006 Robert F. Furchgott Award RecipientsThe Robert F. Furchgott Award for Excellence in ResearchAwardee: Richard Pomerantz, Ph.D. 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. « Back to Top |