Course Overview - Oct. 3 (Biochem 230 information and tips on critical reading)

Paper#1: Ioannidis, J.P. (2005). "Contradicted and initially stronger effects in highly cited clinical research." JAMA. 294(2):218-28.

Discussion#1 - Oct. 7 (Cox-2 inhibitors: A cautionary tale)

Paper 1: Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. (2004). "Risk of cardiovascular events and rofecoxib: cumulative meta-analysis." Lancet. 364(9450):2021-9.

Paper 2: Egan KM, Lawson JA, Fries S, Koller B, Rader DJ, Smyth EM, Fitzgerald GA. (2004). "COX-2-derived prostacyclin confers atheroprotection on female mice." Science. 306(5703):1954-7.

Background: Flower RJ. (2003). "The development of COX2 inhibitors." Nat Rev Drug Discov. 2(3):179-91.

Topol EJ (2004). "Failing the public health--rofecoxib, Merck, and the FDA." N Engl J Med. 351(17):1707-9.

Kim PS, Reicin AS. (2004). "Rofecoxib, Merck, and the FDA." N Engl J Med. 351(27): 2875-8.

Discussion#2 - Oct. 14 (Evolution of antibiotic resistance)

Paper 1: Cirz RT, Chin JK, Andes DR, de Crecy-Lagard V, Craig WA, Romesberg FE.(2005)."Inhibition of mutation and combating the evolution of antibiotic resistance." PLoS Biol. 3(6):e176.

Paper 2: Miller LG, Perdreau-Remington F, Rieg G, Mehdi S, Perlroth J, Bayer AS, Tang AW, Phung TO, Spellberg B. (2005). "Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles." N Engl J Med. 352(14):1445-53.

Paper 3: Kazakova SV, Hageman JC, Matava M, Srinivasan A, Phelan L, Garfinkel B, Boo T, McAllister S, Anderson J, Jensen B, Dodson D, Lonsway D, McDougal LK, Arduino M, Fraser VJ, Killgore G, Tenover FC, Cody S, Jernigan DB. (2005)."A clone of methicillin-resistant Staphylococcus aureus among professional football players." N Engl J Med. 352(5):468-75.

Background:

Walsh C. (2000). "Molecular mechanisms that confer antibacterial drug resistance." Nature. 406(6797):775-81.

Hughes D. (2003). "Exploiting genomics, genetics and chemistry to combat antibiotic resistance." Nat Rev Genet. 4(6):432-41.

Oliveira D.C, Tomasz A., de Lencastre H. (2002). "Secrets of success of a human pathogen: molecular evolution of pandemic clones of meticillin-resistant Staphylococcus aureus." Lancet Infect Dis. 2(3):180-9.

Discussion#3 - Oct. 21 (Protein conformation as drug target: HIV fusion inhibitors)

Paper 1: Lau A, Swinbank KM, Ahmed PS, Taylor DL, Jackson SP, Smith GC, O'Connor MJ. (2005). "Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase."Nat Cell Biol. 7(5):493-500.

Paper 2: O'Hearn M, Montaner JS, Piliero PJ, Trottier B, Walmsley S, Cohen C, Kuritzkes DR, Eron JJ Jr, Chung J, DeMasi R, Donatacci L, Drobnes C, Delehanty J, Salgo M; TORO 1 Study Group (2003). "Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America." N Engl J Med 348(22): 2175-85.

Background:

Sepkowitz, K. A. (2001). "AIDS--the first 20 years." N Engl J Med 344(23): 1764-72.

Chan, D. C. and P. S. Kim (1998). "HIV entry and its inhibition." Cell 93(5): 681-4.

Discussion #4 - Oct. 28 (Allele-specific treatments for cystic fibrosis)

Paper 1: Wilschanski M, Yahav Y, Yaacov Y, Blau H, Bentur L, Rivlin J, Aviram M, Bdolah-Abram T, Bebok Z, Shushi L, Kerem B, Kerem E. (2003). "Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations." N Engl J Med. 349(15):1433-41.

Paper 2: Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ. (2004). "Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects." Science. 304(5670):600-2.

Background:

Rowe SM, Miller S, Sorscher EJ. (2005). "Cystic fibrosis." N Engl J Med. 352(19):1992-2001.

Sayeed A., Ng D.T. (2005). "Search and destroy: ER quality control and ER-associated protein degradation." Crit Rev Biochem Mol Biol. 40(2):75-91.

Discussion#5 - Nov. 4 (EGF-R mutations and human variation in lung cancer treatment)

Paper 1: Fabian MA et al. (2005). "A small molecule-kinase interaction map for clinical kinase inhibitors." Nat Biotechnol. 23(3):329-36.

Paper 2: Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (2004). "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib." N Engl J Med. 350(21):2129-39.

Background: Rowinsky EK (2004). "The erbB family: targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors." Annu Rev Med. 55:433-57.

Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. (2002). "The Protein Kinase Complement of the Human Genome." Science 298: 1912-1934. Genome Chart

Discussion #6 - Nov. 11 (Hypercholesterolemia: Beyond statins)

Paper 1: Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, Elbashir S, Geick A, Hadwiger P, Harborth J, John M, Kesavan V, Lavine G, Pandey RK, Racie T, Rajeev KG, Rohl I, Toudjarska I, Wang G, Wuschko S, Bumcrot D, Koteliansky V, Limmer S, Manoharan M, Vornlocher HP. (2004). "Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs." Nature. 432(7014):173-8.

Paper 2: Youssef, S., O. Stuve, et al. (2002). "The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease." Nature 420(6911): 78-84.

Background: Alberts, A. W., J. Chen, et al. (1980). "Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent." Proc Natl Acad Sci U S A 77(7): 3957-61.

Wekerle, H. (2002). "Tackling multiple sclerosis." Nature 420(6911): 39-40.
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Nominations Billboard (Nov. 14 is the cut off for nominations!)

Discussion#7 - Nov. 18 (The obesity epidemic and the CNS)

Paper 1: Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S; RIO-Europe Study Group. (2005). "Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study." Lancet. 365(9468):1389-97.

Paper 2: Fan, W., B. A. Boston, et al. (1997). "Role of melanocortinergic neurons in feeding and the agouti obesity syndrome." Nature 385(6612):165-8.

Background:

Barsh, G. S. and M. W. Schwartz (2002). "Genetic approaches to studying energy balance: perception and integration." Nat Rev Genet 3(8): 589-600.

Kopelman, P. G. (2000). "Obesity as a medical problem." Nature 404(6778): 635-43.

Discussion#8 - Nov. 28 (Discussion of papers selected by students)

Paper 1: Taubenberger et al (2005) "Characterization of the 1918 influenza polymerase genes." Nature 437: 889-893.

Background:

Terrence M . Tumpey et al. (2005). " Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus" Science 310: 77-80.

Sharp, P. (2005). "1918 Flu and Responsible Science" Science Editorial 310: 17.

Horimoto, T. and Kawaoka, Y. (2005). "Influenza: Lessons from past pandemics, warnings from current incidents." NATURE REVIEWS MICROBIOLOGY 3: 591-600.

Discussion#9 - Dec. 2 (More Discussion of papers selected by students)

Paper 1: Druilhe P, Spertini F, Soesoe D, Corradin G, Mejia P, et al. (2005) "A Malaria Vaccine That Elicits in Humans Antibodies Able to Kill Plasmodium falciparum." PLoS Med 2(11): e344.

Paper 2: Bruce Giffin, Peter McCann, Alan Bitonti and Cyrus Bacchi (1986). "Polyamine Depletion Following Exposure to DL-alpha-Difluormethylornithine Both In Vivo and In Vitro Initiates Morphological Alterations and Mitochondrial Activation in a Monomorphic Strain of Trypanosoma brucei brucei."  J. Protozool. 33(2) 1986, 238-243

Background:

(For paper#1) Vasee S. Moorthy, Michael F Good, Adrian V S Hill (2004). "Malaria vaccine developments." The Lancet 363: 150.

(For paper#1) Brian M Greenwood, Kalifa Bojang, Christopher J M Whitty, Geoffrey A T Targett (2004). "Malaria" The Lancet 365:1487-1495.


(For paper#2) Bacchi, CJ and Yarlett, N. (2002). "Polyamine Metabolism as Chemotherapeutic target in Protozoan Parasites". Mini Reviews in Medicinal Chemistry 2:553-563.

(For paper#2) Bitonti, AJ et al. (1986)."Necessity of antibody response in the treatment of African trypanosomiasis with a-Difluoromethylornithine." Biochemical Pharmacology 35(2):331-334.