Topics in Molecular Medicine

Syllabus

Fall, 2011

Topics in Molecular Medicine
Wednesdays (unless noted) from 3:30 pm - 4:15 pm in room 901 BRB
Breakout sessions from 4:15 pm - 5:00 pm in room 1001 BRB

Class #1 – Nancy Spinner/Ian Krantz – September 7 - "Autism genetics"

• Muhle R, Trentacoste SV, and Rapin I (2004): The Genetics of Autism. Pediatrics 113(5):e472-86. [pdf]
• Levy D, Ronemus M, Yamrom B, Lee Y, Leotta A, Kendall J, Marks S, Lakshmi B, Pai D, Ye K, Buja A, Krieger A, Yoon S, Troge J, Rodgers L, Iossifov I, and Wigler M (2008): Rare De Novo and Transmitted Copy-Number Variation in Autistic Spectrum Disorders. Neuron 70:886-97. [pdf]

Class #2 – Andy Minn – September 14 - "Recent molecular insight on metastasis and its impact on clinical management"

• Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, et. al. (2010): Genome remodeling in a basal-like breast cancer metastasis and xenograft. Nature 464(7291):999-1005. [pdf]
• Shah SP, Morin RD, Khattra J, Prentice L, Pugh T, Burleigh A, Delaney A, Gelmon K, Guliany R, Senz J, Steidl C, Holt RA, Jones S, Sun M, Leung G, Moore R, Severson T, Taylor GA, Teschendorff AE, Tse K, Turashvili G, et. al. (2009): Mutational evolution in a lobular breast tumor profiled at single nucleotide resolution. Nature 461(7265):809-13. [pdf]
• Samuel Hellman (1994): Natural History of Small Breast Cancers, Karnofsky Memorial Lecture. [pdf]

Class #3 – Joshua Friedman– September 21 - "Cellular alchemy: Making fibroblasts (lead) into hepatocytes (gold)”

• Prakash R and Mullen KD (2010): Mechanisms, diagnosis and management of hepatic encephalopathy. Nat. Rev. Gastroenterol. Hepatol. 7: 515–525. [pdf]
• Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, Hu Y, Wang X, and Hui L (2010): Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature475(7356):386-9. [pdf]

Class #4 – Mitch Lazar – September 26 (Monday) - "Adipocyte triglyceride lipase (ATGL) in human metabolic disease"

• Das SK, Eder S, Schauer S, Diwoky C, Temmel H, Guerti B, Gorkiewicz G, Tamilarasan KP, Kumari P, Trauner M, Zimmermann R, Vesely P, Haemmerie G, Zechner R, Hoefler G (2011): Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 333(6039): 233-8. [pdf]
• Schweiger M, Lass A, Zimmerman R, Elchmann TO, Zechner R (2009): Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. Am J Physiol Endocrinal Metab 297(2): E289-96. [pdf]
• Lass A, Zimmermann R, Oberer M, Zechner R (2011): Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Prog Lipid Res 50(1):14-27. [pdf]

Class #5 – Mark Kahn– October 5 - "Tumor vessels are Eph-ing hard to block"

• Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy A, Deutsch U, Luthi U, Barberis A, Benjamin LE, Makinen T, Nobes CD, Adams RH (2010): Ephrin-B2 controls VEGF-induced angiogenesis and lympangiogenesis. Nature 465(7297): 483-6. [pdf]
  
  • Complimentary subsequent article: Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, Acker T, Acker-Palmer A (2010): Ephrin-B2 regulates VEGFR2 function in developmental and tumor angiogenesis. Nature 465(7297): 487-91. [pdf]
• Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004): Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. NEJM 350(23): 2335-42. [pdf]
  
  • Supplemental clinical article: Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007): Paclitaxel plus bevacizumab versus paclitaxel alone for matastatic breast cancer. NEJM 357(26):2666-76. [pdf]
• Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, Inoue M, Bergers G, Hanahan D, Casanovas O (2009): Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15(3):220-31. [pdf]

Class #6 – Gerd Blobel – October 10 (Monday) - “Targeting chromatin components to treat leukemias”

• Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, Magoon D, Qi J, Blatt K, Wunderlich M, Taylor MJ, Johns C, Chicas A, Mulloy JC, Kogan SC, Brown P, Valent P, Bradner JE, Lowe SW, Vakoc CR: RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukemia. Nature August 2011 (Epub ahead of print). [pdf]
  
  • Supplemental data [pdf]
• Chen J, Odenlike O, Rowley JD (2010): Leukaemogenesis: more than mutant genes. Nat Rev Cancer 10(1):23-36. [pdf]

Class #7 – Peter Crino – October 17 (Monday) - "mTOR Signaling: A Crossroad for Autism, Epilepsy, Malformations, and Tumors

• Ehninger D and Silva AJ (2011): Rapamycin for treating Tuberous sclerosis and Autism spectrum disorders. Trends Mol Med 17(2):78-87. [pdf]
• Wang X and Proud CG (2010): mTORC1 signaling: What we still don't know. J Mol Cell Biol 3(4):206-20. [pdf]

Class #8 – Rahul Kohli – October 19 - "Targeting pathogen virulence in Neisseria meningitides"

• Chamot-Rooke J, Mikaty G, Malosse C, Soyer M, Dumont A, Gault J, Imhaus AF, Martin P, Trellet M, Clary G, Chafey P, Camoin L, Nilges M, Nassif X, Dumenil G (2011): Posttranslational modification of pili upon cell contact triggers N. meningitidis dissemination. Science 331(6018):778-82. [pdf]
• Tan LK, Carlone GM, Borrow R (2010): Advances in the development of vaccines against Neisseria meningitidis. NEJM 362(16):1511-20. [pdf]

Class #9 – Robert Doms – October 26 - "Reconstructing Berlin: A possible cure for HIV”

• Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks GM, Kohn DB, Gregory PD, Holmes MC, Cannon PM (2010):Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol 28(8):839-47. [pdf]
• Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, Schneider T, Hofmann J, Kucherer C, Blau O, Blau IW, Hofmann Wk, Thiel E (2009): Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. NEJM 360(7):692-8. [pdf]
• Background Review
  
  • Deeks SG and McCune JM (2010): Can HIV be cured with stem cell therapy? Nat Biotechnol 28(8):807-10. [pdf]

Class #10 – Jonathan Maltzman – November 2 - “Improving Immunosuppression through rational drug design”

• Larsen CP, Pearson TC, Adams AB, Tso P, Shirasugi N, Strobert E, Anderson D, Cowan S, Price K, Naemura J, Emswiller J, Greene J, Turk LA, Bajorath J, Townsend R, Hagerty D, Linsley PS, Peach RJ (2005): Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-lg with potent immunosuppressive properties. Am J Trasplant 5(3):443-53. [pdf]
• Harrison’s Chapter 276: Transplantation in the Treatment of Renal Failure. 1-16. [pdf]
• Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G, Lang P, Grinyo J, Halloran PF, Solez K, Hagerty D, Levy E, Zhou W, Natarajan K, Charpentier B; Belatacept Study Group (2005): Costimulation blockade with belatacept in renal transplantation. NEJM 353(8):770-81. [pdf]
• Philip F. Halloran, M.D., Ph.D. Immunosuppressive Drugs for Kidney Transplantation. NEJM  351:26 2715-2730, 2004. [pdf]

Class #11 – Josh Dunaief – November 9 - "Inhibition of VEGF and the complement cascade: Eye opening bench-to-bedside therapies for age-related macular degeneration”

• Bird AC (2010): Therapeutic targets in age-related macular disease. JCI 120(9):3033-41. [pdf]
• Shima DT, Adamis AP, Ferrara N, Yeo KT, Yeo TK, Allende R, Folkman J, D'Amore PA (1995): Hypoxic induction of endothelial cell growth factors in retinal cells: Indentification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol Medicine 1(2):182-93. [pdf]
• Nazaki M, Raisler BJ, Sakurai E, Sarma JV, Barmum SR, Lambris JD, Chen Y, Zhang K, Ambati BK, Baffi JZ, Ambati J (2006): Drusen complement components C3a and C5a promote choroidal neovascularization. PNAS 103(7): 2328-33. [pdf]

Class #12 –Warren Pear – November 16 - “Targeting Notch in T cell leukemia”

• Wu Y, Cain-Hom C, Choy L, Hagenbeek TJ, de Leon GP, Chen Y, Finkle D, Venook R, Wu X, Ridgway J, Schalin-Reed D, Dow GJ, et. al. (2010): Therapeutic antibody targeting of individual Notch receptors. Nature 464(7291):1052-59. [pdf]
  • Supplementary Information [pdf]
• Pui CH, Robison LL, Look AT (2008): Acute lymphoblastic leukaemia. Lancet 371(9617):1030-43. [pdf]
• Ferrando AA (2009): The role of NOTCH1 signaling in T-ALL. Hematology 353-361. [pdf]

Class #13 – Aimee Payne – November 30 - "Gene therapy and beyond!"

• M. Peter Marinkovich, Paul A. Khavari, G. Scott Herron and Eugene A. Bauer: Inherited Epidermolysis Bullosa. Chapter 65, DIGM Review. 596-609. [pdf]
• Woodley DT, Keene DR, Atha T, Huang Y, Lipman K, Li W, Chen M (2004): Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa. Nat Med 10(7): 693-5. [pdf]

Class #14 – Brad Johnson – December 7 - " Progeria”

• Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, Panopoulos AD, Suzuki K, Kurnian L, Walsh C, Thompson J, Boue S, Fung HL, Sancho-Martinez I, Zhang K, Yates J 3rd, Izpisua Belmonte JC (2011): Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472(7342):221-5. [pdf]
• Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith AC, Perry MB, Brewer CC, Zalewski C, Kim HJ, Solomon B, et. al. (2008): Phenotype and course of Hutchinson-Gilford progeria syndrome. NEJM 358(6):592-604. [pdf]
• Optional review: Misteli T (2011): HGPS-derived iPSCs for the ages. Cell Stem Cell 8(1):4-6. [pdf]
  

Class #15 – Bob Vonderheide – December 14 - "Improving Cancer Vaccines"

• Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT (2010): Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 330(6005):827-30. [pdf]
• Finn OJ (2008): Cancer Immunology. NEJM 358(25):2704-15. [pdf]
  

• Last updated: 10/03/2011