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<\/a>In one of the classes that Manuel Ascano, PhD,<\/strong> teaches to graduate students, he shows a slide with two long sequences of RNA.<\/p>\n \u201cI ask if anyone in the class can identify the first or second sequence, and of course they can\u2019t. The sequences just look like random stretches of ACGUs,\u201d said Ascano, assistant professor of Biochemistry, referring to the chemical bases that compose RNA \u2014 the messenger of genetic information encoded by DNA.<\/p>\n Somehow though, he tells the students, proteins in our cells \u201cknow\u201d that the first sequence is from the bacterium that causes cholera and the second is from human tubulin.<\/p>\n \u201cHow do these proteins know? This is the core curiosity that drives our research,\u201d Ascano said.<\/p>\n Ascano and his team are looking for proteins that respond to RNA viruses at the earliest moments of interaction between virus and cell. And they\u2019re doing it in a unique way, using new technologies they\u2019ve developed to isolate and identify RNA-binding proteins.<\/p>\n Of the 260 or so viruses that are known to cause human disease, about 60% use RNA instead of DNA as their genetic material. These include viruses that cause flu, Ebola, HIV and SARS.<\/p>\n \u201cThese viruses are basically RNA wrapped up in a package,\u201d Ascano said. \u201cOur tools are made for exploring this moment of \u2018first contact\u2019 between the incoming viral RNA and the proteins that will recognize the virus and shut it down or be fooled and hijacked for the virus\u2019 use.\u201d<\/p>\n The son of two physicians, Ascano grew up in Queens, New York, listening to dinner-table discussions about science and medicine and watching videos of surgeries with his dad. During college at the University of Illinois at Urbana-Champaign, his interest in medicine shifted to scientific discovery.<\/p>\n \u201cI realized that I wanted to be working \u2018upriver,\u2019 at the source of the discoveries,\u201d Ascano said.<\/p>\n He earned his PhD in biochemistry from the University of Cincinnati and studied RNA biology during a postdoctoral fellowship at The Rockefeller University.<\/p>\n Along the way, he contributed to a basic science discovery that has moved rapidly to a drug being tested in phase I clinical trials. He and his colleagues at Rockefeller found a unique chemical bond in the product of an enzyme that senses foreign DNA in the cell and activates the protein STING, which fires up the innate immune response. The \u201cenzymatic quirk\u201d they discovered has informed efforts to develop a new class of cancer immunotherapy drugs.<\/p>\n \u201cI was looking at this from a purely basic science perspective. It\u2019s humbling to see something you\u2019ve discovered end up in the clinic,\u201d Ascano said. \u201cI don\u2019t expect that to happen very often, but it\u2019s great when it does.\u201d<\/p>\n Ascano joined the Vanderbilt faculty in 2014. He and his wife, Janice, also a PhD-trained scientist, have two children.<\/p>\n <\/p>\n <\/p>\n Erin Calipari, PhD,<\/strong> is not intimidated by the complexity of the human brain. She\u2019s trying to understand the neural circuits that control motivation and decision-making.<\/p>\n \u201cI know that the brain is complicated, but I think it\u2019s made up of a series of predictable events,\u201d said Calipari, assistant professor of Pharmacology. \u201cWe\u2019re studying at the cellular and molecular level how animals make decisions to seek rewarding stimuli and avoid negative stimuli, and how exposure to drugs of abuse dysregulates that code.\u201d<\/p>\n Calipari discovered her passion for science when she was a student at the University of Massachusetts. She loved one of her science courses so much that she turned in a 20-page experimental design proposal for a \u201cfun\u201d end-of-course project. The professor promptly invited her to do research in his laboratory, which focused on drug abuse in animal models. She was hooked.<\/p>\n \u201cIt was the greatest thing, and I ended up spending so many hours in that lab,\u201d Calipari said.<\/p>\n The experience prepared Calipari for graduate studies at Wake Forest University, where she explored drug addiction in behavioral animal models and analyzed neurotransmitter release in the brain using analytical chemistry techniques that she and her colleagues developed.<\/p>\n During her postdoctoral fellowship at Icahn School of Medicine at Mount Sinai, Calipari expanded the range of technologies she uses \u2014 both in brain tissue and in awake and behaving animals \u2014 to probe the neural circuits underlying drug abuse and addiction.<\/p>\n \u201cI try to ask really good innovative questions and to use new technologies … to take us a step further than we\u2019ve been before,\u201d said Calipari, who joined the Vanderbilt faculty in 2017. \u201cThat\u2019s part of the fun of science \u2014 you always get to do something new.\u201d<\/p>\n Calipari is excited about recent discoveries in her laboratory examining sex differences in drug abuse vulnerability. Using animal models, she and her team have found that estrogen increases the brain\u2019s cocaine reward signaling and makes females more likely to respond to \u201ccues\u201d that lead to relapse. The findings may point to different processes for drug addiction in men and women and suggest the need for different treatment strategies.<\/p>\n As a member of the Vanderbilt Center for Addiction Research, Calipari values being in close proximity to clinicians and patients.<\/p>\n \u201cWe\u2019re studying the basic mechanisms of how the brain works and how organisms make decisions, and we\u2019re doing this in the context of a disease process that\u2019s critical for public health,\u201d she said. \u201cWe look forward to working with our clinical colleagues to move basic science discoveries into translational studies.\u201d<\/p>\n In her free time, Calipari enjoys rooting for the University of Kentucky men\u2019s basketball team, coached by her father, John Calipari.<\/p>\n <\/p>\n<\/a>