Molecular Oncology

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Molecular Oncology

• Basic Research in Oncology on a floor closely
  integrated with Cell Bio, Biochem, Mol Bio
  Pharm, Molecular Imaging Center
• Integration of physician scientists, basic
  scientists, graduate students, and postdoctoral
  fellows
• Strong education program (journal clubs,
  work-in-progress, didactic courses, training
  grant)
• Cell Biology Colleagues
• Helen Piwnica-Worms PhD, CDC25 Cell Cycle
  Regulation
• Ken Blumer PhD, G protein signaling
• Sheila Stewart PhD, Telomerase

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Regulation of ApoptosisEmily Cheng MD PhD
Kim et al. Nat Cell Biol. 2006 81348

• How do "BH3-only" molecules integrate specific
  death signals to activate "multidomain" BAX/BAK
• What higher order multi-protein complexes at the
  mitochondrion regulate apoptosis and
  mitochondrial homeostasis
• How can we apply the information obtained from
  studies of death regulators to develop novel
  anti-cancer therapeutics.
• Proteomics and Mouse Genetic Models

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Taspase 1 Regulation of MLL Cleavage in
Development and NeoplasiaJim Hsieh MD PhD

• What is the biological significance of Taspase1
  and
• its regulation?
• Are there unidentified Taspase1 substrates?
• How is MLL and its effect on cell cycle
  progression regulated by ubiquitin-proteasome
  system?
• Can Taspase1 inhibitors be used in cancer
  therapeutics?

Liu et al Genes Dev. 2007 212385
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Arf Nucleophosmin Regulation of Ribosome
Function in CancerJason Weber PhD

• What are the
• basic mecha-
• nisms for ARFs tumor suppressive capabilities?
• How does ARF antagonize ribosome processing as
  well as the nucleocytoplasmic shuttling of
  maturing ribosomal components?

Nucleophosmin
Apicelli et al. Mol Cell Biol. 2008 In press
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Molecular mechanisms for tumor cell metastasis to
bone Katherine Weilbaecher MD
Tumor growth is increased in bone but not in lung
or s.c. tissue of CXCR4-/- mice

• What are the molecular mechanisms behind
  tumor/platelet enhancement of bone mets
• What are the molecular mechanisms of Tax oncogene
  induced bone disease?
• What is the role of SDF-1/CXCR-4 interaction in
  tumor cell homing to bone?

Hirbe et al. PNAS 2007 104 14062
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Human T Cell Leukemia Virus Tax Transgenic Mice
Effects of NF?B Overexpression Lee Ratner MD PhD
Why are these tumors resistant to induction of
apoptosis? (XIAP) What is role of p53 in tumor
dissemination? Is IL15 a proliferation
stimulus? How does blockade of NF kB lead to
tumor regression? Approaches siRNAs, knockout
mice, gene arrays, small molecule inhibitors
Bernal et al. Proc Natl Acad Sci U S A. 2006
1039220
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Didactic Course
Courses started in 1999 Alternating years D
Wilson L Ratner (emphasis on pediatric vs adult
oncology
Schedule for 2008 Course Jan 22 Lee
Ratner Introduction Jan 29 Rick Wilson Cancer
Genomics Feb 5 Jason Weber mTOR Feb 12 Ron
Bose Her2/ErbB signaling Feb 19 Greg
Longmore Epithelial-mesenchymal transition Feb
26 John Cooper Cytoskeletal rearrangement in
cancer Mar 4 Graham Colditz Breast cancer
prevention Mar 12 David Piwnica- Imaging
protein-protein interactions Worms Mar 19 John
DiPersio Manipulating gvhd Apr 1 Tej Pandita ATM
DNA Repair Apr 8 Tim Ley NK and T cell
anti-tumor activity To Be Scheduled Rafi
Kopan Notch signaling Lee Ratner NFkB activation
in cancer Jeffrey Arbeit Angiogenesis and
HIF-1 Student-Sponsored Speaker
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Oncology Fellowship Protocols

• Initiated in 2002
• Overseen by Drs Ratner, Picus, Weilbaecher,
  Graubert, Vij
• 24 protocols written as of Jun, 2007
• 14 protocols in BMT, 9 in Med Onc, 1 in Heme
• 13/15 received PRMC approval within 6 mos as of
  Jan, 2006
• 11/15 had received external funding
• 10/13 received HSC approval within 2 mos
• 5/10 had enrolled patients

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