Research

We are interested in the longevity of the mind. To achieve it, one would need to maintain the capacity to learn and memorize, regardless of age. Nature may have equipped us with such ability – the center for learning and memory, hippocampus, is the major site where neural stem cells reside in the mammalian brain, including humans.

These cells produce new neurons daily. The newborn neurons have been associated with learning and memory as well as mood control. Thus, adult neurogenesis has important implications for human health. Recent studies have estimated that in the human brain, 700 newborn neurons are incorporated in the hippocampal circuitry per day.

Many more are born, but do not survive for unknown reasons. In addition, the number of primary stem cells that generate newborn neurons declines over time, leading to decline in the number of surviving newborn neurons. The question is: Can we influence neurogenesis and harness this natural capacity of the human brain to achieve longevity of the mind?

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To decipher basic mechanisms of adult neural stem cell fate and function

Our goal is to develop strategies that will allow targeted, need-based, safe, and long-term modifications of adult neurogenesis for neurogenesis sustained throughout life. We focus on two major issues: survival of newborn cells and neural stem cell decline over time. Both affect the number of new, functional neurons. We are particularly keen to explore interactions between diverse cell types in the neurogenic niche, a very dynamic community of various cell types residing in a spatially restricted environment. We use a variety of mouse models, genetic and microscopy tools, chemistry, electrophysiology, and behavioral analysis to test a variety of questions pertaining to neural stem cell fate and function. Why do neural stem cells behave differently than other stem cells, which can enter into a quiescent mode and re-enter the cell cycle when needed? What makes them irreversibly exit cell cycle – an intrinsic pre-programmed mechanism or signaling that comes from other cells that reside in the niche? Can we prevent this fate or even reverse their terminal transformation? The answers to these questions will be important not only for the elucidation of the mechanisms that exert molecular and cellular control over neural stem cells, but also for the potential preservation and expansion of this unique source of new neurons in the adult hippocampus.[/vc_column_text]
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To develop analytical algorithms applicable to both basic science and clinical practice

One of the technologies we use for bench-to-bed translation is magnetic resonance. We study both structure of the cells that comprise neurogenic niche and their function – specifically, metabolism. Metabolism is heavily influenced by environment (diet, exercise, infection, toxins), and we are interested to determine how changes in metabolism affect neurogenesis. To measure metabolites, we use complementary methodologies called Nuclear Magnetic Resonance (NMR – for testing samples in a tube) and Magnetic Resonance Spectroscopy (MRS – for testing living human brain). Here, we work on computational algorithms to automate the analysis of complex high-dimensional data we obtain by NMR and MRS, to enable fast and reproducible analysis of any sample. These methods are envisioned as the first step toward personalized mobile devices that could provide instantaneous knowledge on the constituents of the blood, urine, saliva, or any given tissue.

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To discover biomarkers for early diagnosis of human brain disorders as well as new therapeutic targets for their treatment

The ability to diagnose and predict the course of a disease is a pressing goal in clinical medicine. However, for most of neurological disorders, the specific biomarkers of the disease are not known. The diagnosis relies on clinical or radiological criteria. The patient response to treatment is also qualitative, and clues about the course and prognosis of the disease are very limited. In most cases, there are no precise and clinically valuable biomarkers that will enable early diagnosis, treatment evaluation, and prognosis of the disease. Therefore, over the past decade, the search for diagnostic and prognostic biomarkers of specific disorders has escalated. Using advanced computational methods, our goal here is to generate extraordinarily detailed maps of the normal human brain as it changes over the course of the lifespan, and to compare them to the brain maps from a wide variety of patients. We are interested in conditions associated with neurogenesis, such as abnormal learning and memory (learning disabilities, autism, dementia, chronic diseases with declining cognitive function) as well as mood (depression, bipolar disorder, anxieties). To map the brain, we use multimodal neuroimaging, radiomics and metabolomics, and determine so called “radiome sequence”. In essence, radiome is information content of a single pixel in the MRI scan. The radiome depends on the molecular, cellular, and pathological status of the tissue. Thus, by mapping the radiome of the human brain to an unprecedented detail, we enable discovery of new features of the diseased living brain. Such discoveries are then expected to prompt mechanistic invest

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[rs_image_block align=”align-center” image_link=”yes” image=”3337″ link=”url:http%3A%2F%2Fwww.thinksavatic.org%2Fresearch%2Fadult-neurogenesis%2F|title:Adult%20Neurogenesis||” margin_bottom=”20px”][rs_link align=”center” link_text=”Adult Neurogenesis” link=”url:http%3A%2F%2Fwww.thinksavatic.org%2Fresearch%2Fadult-neurogenesis%2F|title:Adult%20Neurogenesis||”]
[rs_image_block align=”align-center” image_link=”yes” image=”3335″ link=”url:http%3A%2F%2Fwww.thinksavatic.org%2Fresearch%2Fautism-biomarkers%2F|title:Autism%20Biomarkers||” margin_bottom=”20px”][rs_link align=”center” link_text=”Clinical Biomarkers” link=”url:http%3A%2F%2Fwww.thinksavatic.org%2Fresearch%2Fautism-biomarkers%2F|title:Autism%20Biomarkers||”]