Wouldn’t it be great to live life in awe, like children do? To accumulate knowledge and to remember the color, the taste, and the aroma of everything, not to mention the names of friends and people, phone numbers, and the title of a memorable movie? However, with each passing day, these abilities are somehow chipped away.

And then comes the hardship of a disease...Anna’s dad was diagnosed with multiple sclerosis when she was just 12. While the debilitating disease ate away at her dad’s brain, immobilizing and confining him to his bed, Anna’s mom suffered a critical financial crisis and left the family, forcing Anna to step up to fill the absence of both her parents and take charge of her two younger siblings. With advancing technology, science has offered incredible ways to elongate life; to enable people to live with these diseases and to breathe another day. However, can there be more to life than just living to see another day?

For Dr. Mirjana Maletic-Savatic, Assistant Professor of Pediatrics and Neuroscience at Baylor College of Medicine, these people we encounter daily -- whether it be you, me, or the next door neighbor -- comprise the core of her research. Determined to help people achieve the “longevity of the mind,” Dr. Maletic-Savatic studies neurogenesis throughout the entire spectrum of life: from early development of the brain in children to the decline of the brain cells in the elderly. She is also developing new neuroimaging methodologies to facilitate early diagnosis of multiple cognitive disabilities and diseases; had her research been widespread 13 years ago, Anna and her family’s lives may have been drastically different.
   
    To achieve longevity of the mind, 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, the hippocampus, is the major site where neural stem cells reside in the human brain. These cells produce new neurons daily, and are very important for learning and memory as well as mood control. Recent studies have estimated that in the human brain, 700 newborn neurons are incorporated in the hippocampal circuitry per day, suggesting an incredible capacity of this region to regenerate itself. Indeed, 30% of it is replaced in our lifetime, but our ability to produce new neurons substantially declines with age. The Savatic lab aims to understand how we can influence neurogenesis and harness this natural capacity of the human brain to keep our minds sound, safe, and healthy.

Current research interests include:

• Understanding Neurogenesis: A primary research interest of the Savatic lab is to understand the mechanisms that lead to formation of new neurons in the hippocampus, a key region for learning and memory as well as mood control (anxiety, depression). Rather than studying a single gene or a single molecule, Dr. Savatic investigates the whole community of cells and how they influence each other. She focuses on a “mother cell”, the stem cell that produces new neurons, without which there would be no neurogenesis. Accumulated data indicate that the formation of new neurons is not merely static or restorative; rather, this process represents an adaptive response of the brain to our environment and/or internal needs. However, the detailed mechanisms that govern the activation of the “mother cell” to produce a new neuron during diverse experiences is not known. Such knowledge is essential if we are to harness the mechanisms of neurogenesis for adult brain repair, necessary for continued learning, memory, and happy mood.
• Novel Imaging Tools: As “the mind sits in the brain,” to achieve its longevity it is critical to discover biomarkers for early diagnosis of human brain disorders as well as new therapeutic targets for their treatment. This is a daunting task, as current tests are insensitive and the diagnosis comes late for majority of brain disorders. To overcome this roadblock, Dr. Savatic looks at the brain as astrophysicists look at the universe. They too face similar problems of sensitivity. Thus, refining the analytical methods applied in astronomy and many other fields such as economics, mechanical engineering, and bioinformatics, Dr. Savatic is developing new approaches to look at the brain MRIs. By mapping the human brain to an unprecedented detail, the Savatic lab hopes to enable discovery of new features of the diseased brain. Such discoveries are then expected to prompt mechanistic investigations and open new avenues aimed at therapies to recover normal brain functions.
• Environmental Effects on Brain Development: In another major line of research, the lab is developing an integrative systems biology approach to study early developmental disorders such as autism. Even though the brain is an enclosed and protected organ, it is heavily affected by a variety of environmental factors and our way of living, from physical exercise to diet. Dr. Maletic-Savatic hypothesizes that the interaction between certain genetic factors and the environment can perturb the metabolic status of brain tissue, leading to a chain of events that eventually manifests as autism. Using noninvasive brain scanning, she is imaging neonates at high-risk for developing neurological disorders as well as children diagnosed with autism spectrum disorder. Then, the same subjects undergo skin biopsy and in the lab, Dr. Savatic develops neurons and other cells from their skin. Thus, she studies the same child both in real life and in a lab dish. This approach to personalized medicine aims to find new clues how neurons function in autism, to be able to translate the findings from the lab dish to the actual person.