Ludwig Cancer Research Seminars

Seminar 677x100 crop and scale 160310n_0122
 

Wed 20 Jun 2018 from 11:00 to 12:00

NDM Building, Basement seminar room, TDI, Headington OX3 7FZ

The Hippo pathway in cell growth, organ size, and Tumorigenesis

Professor Kun-Liang Guan

The Hippo pathway is crucial in organ size control and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include the protein kinases of MST1/2, MAP4Ks, LATS1/2, the transcription co-activators YAP/TAZ and their DNA binding partners TEADs. LATS phosphorylates... Read more

The Hippo pathway is crucial in organ size control and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include the protein kinases of MST1/2, MAP4Ks, LATS1/2, the transcription co-activators YAP/TAZ and their DNA binding partners TEADs. LATS phosphorylates YAP/TAZ to promote cytoplasmic localization and degradation, thereby inhibiting YAP/TAZ and cell growth. The Hippo pathway is regulated by a wide range of signals, including cell density, GPCR, cellular energy levels, and mechanical cues. We recently discovered that TEAD shuttles to cytoplasm in a Hippo independent manner. Moreover, the Hippo pathway also plays a critical role in suppressing cancer immunity. The emerging role of the Hippo pathway in tumorigenesis suggests potential therapeutic value of targeting this pathway for cancer treatment.

Audience: Members of the University only

Organisers: Christina Woodward

Fri 29 Jun 2018 from 11:00 to 12:00

NDM Building, Basement seminar room, TDI, Headington OX3 7FZ

Rational Design of Artificial Genetic Switches

Professor Hiroshi Suguyama

To produce a genetic switch that turns on specific gene expression, we developed a histone deacetylase (HDAC) inhibitor conjugated to pyrrole–imidazole polyamide (PIP) that has remarkable properties such as sequence-specific DNA binding, effects on cell permeability, and nuclear localization. We... Read more

To produce a genetic switch that turns on specific gene expression, we developed a histone deacetylase (HDAC) inhibitor conjugated to pyrrole–imidazole polyamide (PIP) that has remarkable properties such as sequence-specific DNA binding, effects on cell permeability, and nuclear localization. We constructed a library of 32 types of PIP conjugates that bind to different base sequences and has evaluated gene expression using DNA microarray technology in mice and human cells. We demonstrated that upregulation of gene expression in different transcriptional networks is based on sequence specificity.1 To develop a genetic switch that turns off specific gene expression, we synthesized a functional PIP with a DNA alkylating agent. Our research group found that the functional polyamide targets the mutant (GTT) sequence of Kras codon 12, which is found in colorectal cancer and pancreatic cancer where it effectively suppresses Kras expression.2 We confirmed the compound’s effectiveness in experiments using human colorectal cancer cells and tumor-bearing mice. We have also developed functional polyamides that inhibit the binding of RUNX family genes, which are among the key transcription factors responsible for tumor growth and are drug candidates for the treatment of leukemia, lung cancer, and stomach cancer.3 Therefore, strategies to expand our tunable PIPs could create an epoch-making approach to modulate the desired gene expressions. Recently, we installed cooperative binding host-guest unit to PIP and demonstrated potent cooperative inhibitory effects on gene expression under physiological conditions by disrupting transcription factors- DNA binding.4 In this talk recent progress of regulation of the gene expression using designed PIPs will be discussed.

Audience: Members of the University only

Organisers: Christina Woodward

Thu 5 Jul 2018 from 11:00 to 12:00

NDM Building, Basement seminar room, TDI, Headington OX3 7FZ

Immunological approaches to the treatment of haematological cancers (title tbc)

John Gribben

Audience: Members of the University only

Organisers: Christina Woodward

Thu 4 Oct 2018 from 11:00 to 12:00

NDM Building, Basement seminar room, TDI, Headington OX3 7FZ

Understanding the immune response to persistent human T-cell leukaemia virus (HTLV-I) infections (exact title tbc)

Professor Charles Bangham

Audience: Members of the University only

Organisers: Christina Woodward

Thu 11 Oct 2018 from 11:00 to 12:00

NDM Building, Basement seminar room, TDI, Headington OX3 7FZ

Studying innate immune responses to tissue injury (exact title tbc)

Jelena Bezbradica Mirkovic

Audience: Members of the University only

Organisers: Christina Woodward