Lei Ding, Ph.D. - US grants

Current EEG/MEG based neuroimaging technologies receive limited attentions in functional neuroimaging because their reliable performances have not been successfully demonstrated in sophisticated brain tasks. The need for more reliable, efficient, innovative EEG/MEG neuroimaging technologies that have high spatial and temporal resolutions is urgent. The goal of proposed research is to advance functional neuroimaging technologies in studying human brain functions, via integrating novel techniques from different disciplines, i.e. multi-resolution mathematic models, large-scale computation, advanced signal and image processing, and high-end measurement devices.

Intellectual Merit:

The proposed research consists of applying the well-established L-1 norm regularization technique to a different application domain, namely EEG/MEG image analysis. The problem of image analysis is an undetermined problem, and as such some form of regularization is required. The traditional approach is to apply L-2 norm minimization, which is a valid method when measurement errors are Gaussian random variables. However, when the measurement errors are exponentially distributed, it is more meaningful to use L-1 norm minimization. Moreover, the L-1 optimal solution is supported on a finite (usually small) number of data points, thus naturally taking advantage of the sparse nature of the optimization problem. The novelty of the proposed research is the investigation of sparsity inducing models of neural behavior. In the case of neuro-imaging, it is known from biological factors that during any one millisecond interval, only a tiny fraction of the neurons in the brain "fire". The proposed research therefore has the potential to identify the parameters that describe this behavior. As partial evidence of this, the PI has obtained some preliminary results based on synthetic data, when the correct answer is known, and the results are encouraging.

Broader Impact:

The project will generate novel problem-solving strategies for scientific problems using advanced engineering principles, and to clinical practice for neurological patients through the potential for reduction in loss of life, job, and income. By incorporating authentic learning education activities, we will broaden the participation of all levels of students, K-12 teachers, and other educators, in biomedical research and research educations.

? DESCRIPTION (provided by applicant): Hematopoietic stem cells (HSCs) maintain homeostasis of the blood and immune system throughout life. They are tightly regulated by their microenvironmental niche in the bone marrow. Mounting evidence suggests that chronic myeloid leukemia (CML) arise from mutant HSCs. These diseased leukemia stem cells (LSCs) hijack the HSC mechanisms to sustain the cancer growth and cause relapse. Eradication of LSCs is thus pivotal to cure CML. The discovery of the causing active Bcr/abl kinase mutation in CML and the development of tyrosine kinase inhibitors against Bcr/abl have revolutionized the way we treat CML. Tyrosine inhibitors become the first line of treatment against CML. Although tyrosine kinase inhibitors (e.g. imatinib) can manage the disease, they do not eliminate CML-SCs. A major CML-SC resistant mechanism is the protection offered by the bone marrow niche. Elucidating the niche regulatory mechanisms and target the niche protection mechanisms will help eliminate CML-SCs to better treat CML. However, little is known about the LSC niche. The goal of the proposed research is to characterize how thrombopoietin (TPO), an extrinsic factor, regulates HSCs and LSCs. TPO pathway is required for primitive HSC maintenance in mice and humans. It is not known where Tpo-expressing bone marrow cells create a special niche for primitive HSCs. Furthermore it is not known whether TPO pathway is `hijacked' by CML-SCs for their maintenance. Here, we will identify cellular source of TPO in the bone marrow. Then we will test what cells represent functionally important source for HSC maintenance in vivo. Finally, we will functionally test the role of TPO in CML progression with the focus on CML-SCs in vivo. The results of these studies are expected to not only provide new insights on how the bone marrow niche regulates HSC self-renewal and function, but also have the potential to identify therapeutic targets for CML in the niche.