Course Overview - Oct. 1 (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.

Avorn, J. (2007). "Keeping Science on top in drug evaluation." N Engl J Med. Aug. 16; 357(7):633-5.

Discussion#1 - Oct. 3 (Cox-2 inhibitors: A cautionary tale)

Paper 1: Fries, S. et al. (2006). "Marked Interindividual variability in the Response to Selective Inhibitors of Cyclooxygenase-2." Gastroenterology 130(1):55-64.

Paper 2: North, T.E. et al. (2007). "Prostaglandin E2 regulates vertabrate haematopoietic stem cell homestasis." Nature. Jun. 21; 447(7147):1007-11.

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.

Curfman GD, Morrissey S and Drazen JM (2005). "Expression of Concern: Bombardier et al., 'Comparison of Upper Gastrointestina Toxicity of Refecoxib and Naproxen in Pateints with Rheumatoid Arthritis", N. Engl. J. Med. 2000; 343:1520-8." N Engl J Med. 353:26.

Discussion#2 - Oct. 10 (Combating antibiotic resistance)

Paper 1: Mwangi M. et al. (2007). "Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing." Proc. Natl. Acad. Sci. USA. May 29;104(22):9451-6.

Paper 2: D'Costa V.M. et al. (2006). "Sampling the Antibiotic Resistome." Science Jan. 20;311(5759):374-7.

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. 17 (Proteasome inhibitors in cancer chemotherapy)

Paper 1:Chauhan, D. et al. (2005). "A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib." Cancer Cell. Nov.;8(5):407-19.

Paper 2:Richardson, P.G. et al. (2005). "Bortezomib or high-dose dexamethasone for relapsed multiple myeloma." N. Engl. J. Med. Jun. 16;352(24):2487-98. (Note: you must press the refresh button when viewing this PDF)

Background:

Adams, J. (2002). "Development of the proteasome inhibitor PS-341." Oncologist. 7(1):9-16.

Kyle, R.A., Rajkumar, S.V. (2004). "Multiple myeloma." N. Engl. J. Med. Oct. 28;351(18):1860-73.

Dispenzieri, A. (2005). "Bortezomib for myeloma--much ado about something." N. Engl. J. Med. Jun. 16;352(24):2546-8.

Discussion#4 - Oct. 24 (Diabetes treatments)

Paper 1: Sladek, R. et al. (2007). "A genome-wide association study identifies novel risk loci for type 2 diabetes." Nature. Feb. 22;445(7130):881-5

Paper 2: Teta, M. et al. (2007). "Growth and regeneration of adult beta cells does not invovle specialized progenitors." Dev. Cell. May;12(5):817-26.

Background:

Christensen, K., Murray, J.C. (2007). "What genome-wide association studies can do for medicine." N. Engl. J. Med. Mar. 15;356(11):1094-7.

Moller, D.E. (2001). "New drug targets for type 2 diabetes and the metabolic syndrome." Nature. Dec. 13;414(6865):821-7.

Nathan, D.M., (2007). "Finding new treatments for diabetes--How many, How fast, ...How good?" N.Engl. J. Med. Feb. 1;356(5):437-40.

Discussion#5 - Oct. 31 (Obesity)

Paper 2: Cowley, M.A., et al. (2007). "Diet-induced obestiy causes severe but reversible leptin resistance in arcuate melanocortin neurons." Cell Metab. Mar.;5(3):181-94.

Background: Munzberg, H., Myers, M.G.Jr. (2005). "Molecular and anatomical determinants of central leptin resistance." Nat. Neurosci. May; 8(5): 566-70.

Badman, M.K., Flier, J.S., (2005). "The Gut and engergy balance: Visceral allies in the obesity wars." Science. Mar. 25;307: 1909-14.

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

Emmerson, P.J., et al. (2007). "Melanocortin-4 receptor agonists for the treatment of obesity." Curr. Top Med. Chem. 7(11):1121-30.

Mori.H. et al. (2004). "Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity." Nature 10(7):739-43.

Howard, J.K., et al. (2004). "Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3." Nat. Med. Jul.10(7):734-8.

Paper 2: Day, C.L., et al. (2006). " PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression." Nature Sept. 21; 443:350-54.

Background:

Van Maele, B., et al. (2006). " Cellular co-factors of HIV-1 integration." Trends Biochem. Sci. Feb.;31(2):98-105.

Barber, D.L., et al. (2006). "Restoring function in exhausted CD8 T cells during chronic viral infection." Nature Feb. 9;439(7077):682-7.

Sharpe, A.H., et al. (2007). "The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection." Nat. Immunol. Mar.8;(3):239-45.

Grinsztejn, B. et al. (2007). " Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with mulitdrug-resistant virus: a phase II randomised controlled trial." Lancet. Apr. 14;369(9569):1261-9.

Paper 2: Garcia-Calvo M., et al. (2005). "The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)." Proc Natl Acad Sci U S A. Jun 7;102(23):8132-7.

Background:

Sikorski, JA., (2005). "Oral cholesteryl ester transfer protein (CETP) inhibitors: a potential new approach for treating coronary artery disease." J Med Chem. Jan 12;49(1):1-22.

Yamashita, S. (2000). "Molecular biology and pathophysiological aspects of plasma cholesteryl ester transfer protein." Biochim Biophys Acta. Dec 15;1529(1-3):257-75.

Lowe, D. (2007). "Opinion: In the pipeline."

Clader, J.W. (2004). "The discovery of ezetimibe: a view from outside the receptor." J Med Chem. Jan 1;47(1):1-9.

Davis, H.R. Jr., et al. (2004). "Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis." J Biol Chem. Aug 6;279(32):33586-92.

Altmann, S.W., et al. (2004). "Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption." Science. Feb 20;303(5661):1201-4.

Nov. 19 (NO CLASS - Thanksgiving Holiday)

Nov. 21 (NO CLASS - Thanksgiving Holiday)

Discussion#8 - Nov. 26 (student-led discussion)

Kiel MJ, He S, Ashkenazi R, Gentry SN, Teta M, Kushner JA, Jackson TL, Morrison SJ. "Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU." Nature. 2007 Sep 13;449(7159):238-42. Epub 2007 Aug 29.

Discussion#9 - Nov. 28 (student-led discussion)

Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C, Lowe SW. (2007) "Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas." Nature. Feb 8;445(7128):656-60.