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Termini-John

John Termini, Ph.D.

  • Professor, Department of Molecular Medicine
  • Scientific Director of Shared Resources

John Termini, Ph.D.

Research Focus :
  • Metastatic Brain Tumors
  • Nucleic Acid Chemistry & Biology
  • Metabolic Disease & Cancer

Degrees

  • 1985 - Columbia University, New York, NY, Ph.D. in Chemistry
  • 1981 - Columbia University, New York, NY, M.S./M.Phil. in Chemistry
  • 1980 - Columbia College, New York, NY, B.A. in Chemistry

Fellowship

  • 1987 to 1989 - American Cancer Society Fellowship
  • 1987 to 1989 - California Institute of Technology Faculty Fellowship
  • 1985 to 1986 - Columbia University Fellowship

1. Metabolically induced DNA/RNA damage and human disease

Metabolic syndrome and diabetes increase the risk for certain cancers. We have identified carbohydrate-induced DNA/RNA damage products that may provide a molecular link between these diseases. We were the first to measure one of the major DNA damage products induced by glucose, CEdG, as a significant DNA adduct in humans (~ 1 in 107 dG). It is also significantly elevated in T1 and T2D and correlates with fasting plasma glucose and HbA1c in animal models. We have also shown that CEdG is mutagenic in human cells and contributes to genomic instability, and has few pathways for repair in DNA.  Since diabetics accumulate this adduct and have been shown by others to be compromised in DNA repair, we have proposed that CEdG accumulation as a result of hyperglycemia may enhance the risk for specific cancers.

 

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2. Metabolic targeting in brain cancer

In collaborative studies with Dr. Rahul Jandial in Neurosurgery and Dr. Eugene Roberts we have shown that metastatic breast tumors in the brain acquire the ability to utilize the neurotransmitter GABA to meet energetic demands, as well as acquire other “brain-like” characteristics to allow them to successfully inhabit the neural niche. We have also recently found that targeting the glyoxylase system (GLO1) in glioblastoma can arrest brain tumor development in animal models via a mechanism that involves the accumulation of pro-apoptotic CEdG. Encouraged by these results, we are investigating GLO1 targeting in breast to brain metastases.

 

 

 


3. Metallocorroles for therapeutic and imaging applications in cancer

In collaboration with Profs. Harry Gray of Caltech and Zeev Gross at Technion we have shown that metal containing compounds called metallocorroles possess antitumor activity towards different cancers in a manner that depends upon the identity of the metal ion and the pattern of corrole functional group substitution. These factors profoundly influence the intracellular uptake kinetics, which can be monitored spectrophotometrically due to the intense fluorescence emission of certain metal substituted corroles . We have also established the mechanism of cytotoxic action for some of these compounds, which involves late M phase cell cycle arrest.

 

 

 

Punnajit Lim, Ph.D.
Staff Scientist
 
Staff Scientist
 
Richard Jaramillo
Irell & Manella Graduate Student
 
Alexandra Ciminera  
Irell & Manella Graduate Student   

Josue Barnes  
Student Intern

Information listed here is obtained from Pubmed, a public database; City of Hope is not responsible for its accuracy.

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