Graduate School of Medical Sciences

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M. Flint Beal

Professor

Goals

We have a research team with extensive expertise in translational neuroscience, and we have advanced new therapies into clinical trials in PD, HD and ALS. We have contributed to studies of human IPS cells which have been induced to become dopaminergic neurons. Over the last few years, we have been studying the role of PGC-1α and sirtuins in neurodegenerative diseases, and continue to work to develop novel therapeutic interventions, including transcriptional modulators of the PGC-1alpha, Nrf2/ARE and hemeoxygenase pathways.

The overall long-term goal of the laboratory is to study mechanisms of neurodegeneration in Alzheimer’s Disease, Huntington’s Disease, Parkinson’s Disease and amyotrophic lateral sclerosis, and to devise therapeutic strategies in mouse models of neurodegenerative diseases by combining genetic and pharmacologic approaches to improve mitochondrial function and attenuate oxidative damage. In our laboratory, we test new neuroprotective agents in animal models of neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease and Parkinson’s disease.  These studies will help us understand the role of mitochondrial dysfunction and oxidative damage in the pathogenesis of neurodegenerative diseases. Another goal is to further develop novel neurochemical assays for assessing oxidative damage for use in clinical trials of new therapies for these diseases. Finally, our laboratory aims to gain knowledge of mitochondrial biology in different cell types to determine whether mitochondrial function is related to cell-type specificity in neurodegenerative diseases.  Our studies may contribute to developing new therapies for the treatment of human neurodegenerative diseases.

Achievements

  • We carried out extensive studies in the MPTP model of Parkinson’s Disease (PD), which showed that therapeutic interventions with free radical scavengers, inhibitors of NOS, and coenzyme Q10 were efficacious. 
  • We utilized 3-nitropropionic acid to model HD in rodents and cell lines. 
  • Over the past several years, we made extensive use of transgenic mouse models of neurodegenerative diseases including PD. We developed transgenic mouse models of PINK1 deficiency, and a transgenic mouse with the R1441C mutation in LRRK2, which is linked to PD in man. 
  • We developed a number of treatments, which have shown efficacy in improving the behavioral phenotype, improving survival and reducing neuropathologic damage in transgenic mouse models of neurodegenerative diseases. 
  • We utilized analytical chemistry techniques to measure alterations in neurochemistry, energy metabolites and markers of free radical mediated oxidative damage. 
  • We utilized cell culture and cybrid approaches to measure mitochondrial function in vitro. These studies have been extended to research in human patients. We developed neurochemical assays for measurements of neurotransmitters and oxidative damage markers in plasma and cerebrospinal fluid. 
  • We developed plasma and CSF metabolomics, assays using HPLC with coulometric array detection to develop novel biomarkers for the diagnosis and assessment of treatment of AD, ALS, HD and PD.

Research Topics

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Weill Cornell Medicine
Graduate School of Medical Sciences
1300 York Ave. Box 65 New York, NY 10065 Phone: (212) 746-6565 Fax: (212) 746-5981