Topics in Molecular Medicine

Syllabus

Fall, 2013

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

Class #1 – Roger Greenberg – September 4 - "Targeting Homologous Recombination deficiency in hereditary cancers"

• Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005). Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434(7035):917-21. [pdf]
• Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L, Xu X, Deng CX, Finkel T, Nussenzweig M, Stark JM, Nussenzweig A (2010). 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141(2):243-54. [pdf]
• Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellends JH, de Bono JS (2009). Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. NEJM 361(2): 123-34. [pdf]
  

Class #2 – Aimee Payne – September 11 - "RDEB: 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 #3 – Nancy Spinner & Ian Krantz – September 20 (Friday) - "New diagnostic platforms (exome-genome sequencing) for diagnosing and understanding disease"

• Zaidi S, et. al. (2013). De novo mutations in histone-modifying genes in congenital heart disease. Nature 498(7453): 220-3. [pdf]
  
  • Supplemental data [pdf]
• Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J (2011). Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 12(11):745-55. [pdf]

Class #4 – Robert Vonderheide – September 25 - "The road to personalized cancer vaccines"

• Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R, Magrini VJ, Arthur CD, White JM, Chen YS, Shea LK, Hundal J, Wendl MC, Demeter R, Wylie T, Allison JP, Smyth MJ, Old LJ, Mardis ER, Schreiber RD (2012). Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 482(7385):400-4. [pdf]
• Hacohen N, Fritsch EF, Carter TA, Lander ES, Wu CJ (2013). Getting personal with neoantigen-based therapeutic cancer vaccines. Cancer Immunol Res (epub ahead of print) April 7, 2013. [pdf]
• Background Review
  • Kreiter S, Castle JC, Tureci O, Sahin U (2012). Targeting the tumor mutanome for personalized vaccination therapy. Oncoimmunology 1(5):768-9. [pdf]

Class #5 – Mitch Lazar – October 2 - "A newly discovered mitochondrial pyruvate transporter in metabolic disease"

• Bricker DK, Taylor EB, Schell JC, Orsak T, Boutron A, Chen YC, Cox JE, Cardon CM, Van Vranken JG, Dephoure N, Redin C, Boudina S, Gygi Sp, Brivet M, Thummel CS, Rutter J (2012). A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science 337(6090):96-100. [pdf]
  • Supplemental data [pdf]
• Brivet M, Garcia-Carzorla A, Lyonnet S, Dumez Y, Nassogne MC, Slama A, Boutron A, Touati G, Legrand A, Saudubray JM (2003). Impaired mitochondrial pyruvate importation in a patient and a fetus at risk. Mol Genet Metab 78(3):186-92. [pdf]
• Debray FG, Lambert M, Mitchell GA (2008). Disorders of mitochondrial function. Curr Opin Pediatr 20(4):471-82. [pdf]
• Background Review
  • Divakaruni AS, Murphy AN (2012). Cell biology. A mitochondrial mystery, solved. Science 337(6090):41-3. [pdf]
  • Herzig S, Raemy E, Montessuit S, Veuthey JL, Zamboni N, Westermann B, Kunji ER, Martinou JC (2012). Identification and functional expression of the mitochondrial pyruvate carrier. Science 337(6090):93-6. [pdf]

Class #6 – Brad Johnson – October 9 – "Cell senescence and age-related disease"

• Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232-6. [pdf]
  
• Armanios M (2013). Telomeres and age-related disease: how telomere biology informs clinical paradigms. J Clin Invest 123(3):996-1002. [pdf]
• Background Review
  • Campisi J (2013). Aging, cellular senescence, and cancer. Annu Rev Physiol 75:685-705. [pdf]

Class #7 – Mark Kahn – October 14 (Monday) - "Peripartum cardiomyopathy: An angiogenic disease of the heart"

• Jeng RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, Liu C, West ML, Singer NV, Equinda MJ, Gobourne A, Lipuma L, Young LF, Smith OM, Ghosh A, Hanash AM, Goldberg JD, Aoyama K, Blazar BR, Pamer EG, van den Brink MR (2012). Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med 209(5): 903-11. [pdf]
• Hooper LV, Littman DR, Macpherson AJ (2012). Interactions Between the Microbiota and the Immune System. Science 336: 1268-73. [pdf]
• Bolaños-Meade J, Vogelsang GB (2004): Acute graft-versus-host disease. Clin Adv Hematol Oncol. 2(10): 672-82. [pdf]

Class #8 – Lawrence "Skip" Brass & Scott Diamond – October 23 - "Antiplatelet therapy to prevent heart attacks and strokes: When is enough enough and how do you know?"

• Gachet C, Aleil B: Testing antiplatelet therapy. European Heart Journal Supplements (2008), Vol 10 (Supplement A): A28-A34. [pdf]
• Flamm MH, Colace TV, Chatterjee MS, Jing H, Zhou S, Jaeger D, Brass LF, Sinno T, Diamond SL (2012). Multiscale prediction of patient-specific platelet function under flow. Blood 120(1):190-8. [pdf]

Class #9 – Joshua Friedman – October 30 - "The impact of genomics on inflammatory bowel disease"

• Abraham C, Cho JH (2009). Inflammatory bowel disease. N Engl J Med 361(21):2066-78. [pdf]
• Worthey EA, et. al. (2011). Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med 13(3):255-62. [pdf]

Class #10 – George Shaw – November 6 - “Protection and cure of invading RNA viral pathogens: The Hepatitis C virus paradigm”

• Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM (2011). A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472(7344):481-5. [pdf]
• Rosen HR (2011). Chronic hepatitis C infection. N Engl J Med 364(25):2429-38. [pdf]
• Background Review
  • Liang TJ, Ghany MG (2013). Current and future therapies for hepatitis C virus infection. N Engl J Med 368(20):1907-17. [pdf]

Class #11 – Jonathan Maltzman – November 13 - "Rationally designed immunosuppression"

• Larsen CP, Pearson TC, Adams AB, Tso P, Shirasugu N, Strobert E, Anderson D, Cowan S, Price K, Naemura J, Emswiler 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 Transplant 5(3):443-53. [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. N Engl J Med 353(8):770-81. [pdf]
• Background Review
  • Carpenter CB, Milford EL, Sayegh MH. Chapter 276: Transplantation in the Treatment of Renal Failure. In: Fauci AS, Braunwald E, Kasper D, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008. [pdf]

Class #12 – James Hoxie – November 20 - "HIV reservoirs and the Berlin patient"

• Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF (2012): Stimulation of HIV-1-Specific Cytolytic
  T Lymphocytes Facilitates Elimination of Latent Viral Reservoir after Virus Reactivation. Immunity 36(3):491-501. [pdf]
• Hütter G, Nowak D, Mossner M, Ganepola S, Müssis A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O, Blau IW, Hofmann WK, Thiel E (2009). Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 360(7)692-8. [pdf]
• Background Review
  • Eisele E, Siliciano RF (2012). Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity 37(3):377-88. [pdf]

Class #13 – Gary Wu – December 4 - "Diet, the Gut Microbiota, and Inflammatory Bowel Disease"

• Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB (2012). Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 487(7405):104-8. [pdf]
• Cheifetz AS (2013). Management of active Crohn disease. JAMA 309(20):2150-8. [pdf]
• Supplemental Papers
  • Hou JK, Abraham B, El-Serag H (2011). Dietary intake and risk of developing inflammatory bowel disease: A systematic review of the literature. Am J Gastroenterol 106(4):563-73. [pdf]
  • Kaser A, Zeissig S, Blumberg RS (2010). Inflammatory bowel disease. Annu Rev Immunol 28:573-621. [pdf]

Class #14 – Virginia Lee – December 11 - "Alzheimer's disease therapy: The mystery of vanishing plaques"

• Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA, Landreth GE (2012). ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models. Science 335(6075):1503-6. [pdf]
• Field Response
  • Fitz NF, Cronican AA, Lefterov I, Koldamova R (2013). Comment on "ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models." Science 340(6135):924-c. [pdf]
  • Price AR, Xu G, Siemienski ZB, Smithson LA, Borchelt DR, Golde TE, Felsenstein KM (2013). Comment on "ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models." Science 340(6135):924-d. [pdf]
  • Tesseur I, Lo AC, Roberfroid A, Dietvorst S, Van Broeck B, Borgers M, Moechars D, Mercken M, Kemp J, D'Hooge R, De Strooper B (2013). Comment on "ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models." Science 340(6135):924-e. [pdf]
  • Veeraraghavalu K, Zhang C, Miller S, Hefendehl JK, Rajapaksha TW, Ulrich J, Jucker M, Holtzman DM, Tanzi RE, Vassar R, Sisodia SS (2013). Comment on "ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models." Science 340(6135):924-f. [pdf]
• Author Response
  • Landreth GE, Cramer PE, Lakner MM, Cirrito JR, Wesson DW, Brunden KR, Wilson DA (2013). Response to Comment on "ApoE-Directed Therapeutics Rapidly Clear b-Amyloid and Reverse Deficits in AD Mouse Models." Science 340(6135):924-g. [pdf]
• Background Review
  • Goedert M, Spillantini MG (2006). A century of Alzheimer's disease. Science 314(5800):777-81. [pdf]

Class #15 – Dennis Kolson– December 16 (Monday) - "Microbial translocation and chronic immune activation in HIV neuropathogenesis"

• Brenchley JM, et. al. (2006). Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12(12):1365-71. [pdf]
• Ancuta P, Kamat A, Kunstman KJ, Kim EY, Autissier P, Wurcel A, Zaman T, Stone D, Mefford M, Morgello S, Singer EJ, Wolinsky SM, Gabuzda D (2008). Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One 3(6):e2516. [pdf]
  

• Last updated: 07/30/2013