ALS Research

Our group is devoted to the study of Amyotrophic Lateral Sclerosis. We have the following independent projects.

1)    Biomarker discovery and molecular profiling of ALS. These studies involve the human and mouse, brain and spinal cord tissues. The human tissues are generally from sporadic ALS patients. We perform high spatial resolution MALDI mass spectrometry imaging of tissues and individual neurons, MALDI profiling of tissue homogenates, and top-down proteomics.

2)    Molecules meet epidemiology. We are concerned with how the addition of something as simple as a single methyl group (A4V) to a single protein (amongst 25,000 proteins) can cause ALS. This is an interdisciplinary project that attempts to explain ALS in terms of first physical principles, and is exemplified by Qi Wang’s recent PLoS article.

3)    Therapy development. We have a developed a class of compounds based upon our 2007 JBC manuscript aimed to slow protein aggregation, as well as cell lines that can be used for high throughput, in vitro drug screening.

Biological Mass Spectrometry Research

Our group is one of the best equipped mass spectrometry laboratories in the Northeastern United states. We have new MALDI-TOF, ESI-IonTrap (with ETD), and a dual ESI/MALDI source, 9.4T Fourier transform mass spectrometers, sample handling robots, multidimensional nanoflow HPLC’s, and considerable computational assets. Our mass spectrometry research is driven by the needs of our ALS research, but entails fundamental mass spectrometry research since we must develop many of the tools we need.

1)    MALDI mass spectrometry imaging development. In collaboration with Nathalie Agar’s laboratory we published and have a provisional patent on a method that improves the resolution of MALDI imaging. We perform MALDI TOF and MALDI FTMS imaging.

2)    Top-down mass spectrometry methods development. In collaboration with Bruker Daltonics, we’ve built customized source electronics that allow us to shred proteins into pieces, allowing top-down protein identification on an LC timescale. Murat Karabacak and Jennifer Cobb have manuscripts in review on our findings.

3)    Mass spectrometry computational methods development. Long Li recently published an algorithm for the calculation of the isotopomer distributions, including isotopic fine structure, of large biomolecules. We have also developed novel data preprocessing and classification methods.

4)    Nanofabrication and materials. We are using lithography and focused ion beams to build the surfaces and tools we require.