Current research projects:

1) Elucidation of underlying mechanisms of aging

Aging and life span determination in the model organism C. elegans

Understanding the process of aging is critical for determining whether, and how, aging can be affected and for promoting healthy aging in the elderly. During the past decade, more than fifty longevity assurance genes (LAG) have been identified in Caenorhabditis elegans. We have demonstrated in C. elegans that the standardized extract from Ginkgo biloba leaves EGb 761 increased stress resistance and mean life span, significantly attenuates induced levels of hydrogen peroxide-related reactive oxygen species (ROS) and suppresses expression of the stress response gene hsp-16-2. The central question of this project is whether the positive effect of EGb 761 on longevity involves functional interaction of its active constituents with one or more LAG genes. 
Our preliminary results render this organism an ideal system for evaluating biochemical mechanisms of aging and the mode of action of anti-aging drugs. Results from this study could be applied to other organisms and will provide a basis for possible therapeutic interventions in age-related diseases.

 
2) Natural product drug discovery (specifically for neuroprotection and Alzheimer's disease)

      Natural product drug discovery against Alzheimer’s disease 

Alzheimer’s disease (AD) is one of the most devastating CNS disorders of old age, which leads to a serious public health problem. Currently, there are no drugs with disease-modifying or preventive properties. Development of drugs for this devastating disease still remains a significant challenge. Drug discovery from natural products may involve risks, but has the potential to lead to significant breakthroughs. Aspirin is a successful example of drug discovery from natural products. Herbal extracts such as Ginkgo biloba extract EGb 761, have documented beneficial effects in AD patients, suggesting that some of its natural constituents may be useful for developing drugs for the prevention and treatment of AD. The ongoing projects seek to identify novel compounds against AD using established cellular, invertebrate and mouse models of the disease. Substantial experimental evidence supports the view that Aβ oligomers are responsible for early events that lead to dementia in AD. Previously, we have demonstrated inhibitory effects of EGb 761 on Aβ oligomerization in vitro and in a transgenic C. elegans model of AD. Results from these experiments will provide the rationale for future medicinal chemistry and for identifying other potentially efficacious compounds with desirable activity as potential therapeutic agent to prevent and/or treatment of AD.

Lab members and individual interests:

      Flaubert Tchantchou
      ftchantc@rx.umaryland.edu    

      Exploring the role of Gingko biloba
      in neurogenesis.

                    Yanjue Wu
                    ywu001@umaryland.edu

                                                                               Determining the mechanism of action
                                                                               of Ginkgo biloba on amyloid toxicity.

           Yanan Xu                                                              
           yxu004@umaryland.edu                               

           Signaling pathways affected by β-amyloid and
           neuroprotectants.                                        

                       Marishka Brown                                                                     
                       mbrow004@umaryland.edu                                      

                       Determining the role of serotonin and
                       serotonin receptors in aging and behavioral
                       plasticity.    
 

          Laura Causey                                                                
          lcaus001@umaryland. edu                                            

  Understanding biochemical processes                                     
     that underlie aging using C. elegans                                           
      and metabonomics.                                                                     

Zhiming Cao                     
                                         zcao@rx.umaryland.edu   

                                                     Behavioral studies using mice to   
                                                 define physiological effects of   
                                                        natural neuroprotectants.                

Model systems: