Susan Kraner, PhD, a scientist in Dr. Chris Norris’ lab, joined the UK Sanders-Brown Center on Aging in May 2013. She had worked with Dr. Norris earlier in her career, helping him get started using molecular and viral tools. He continued to develop adeno associated viruses (AAVs) for use in vivo, and needed a molecular biologist who could continue overseeing the development of those tools for him.
Since coming to Sanders-Brown, her work has focused on projects related to characterizing the calcineurin-NFAT (nuclear factor of activated T cells) pathway in tissue and in cell culture. In tissue, she developed EMSA assays (electrophoretic mobility shift assays) that detect the functional binding of the NFAT transcription factors. Higher amounts of NFAT EMSAs are found in tissues from various diseased state subjects, including traumatic brain injury (TBI), and in brains of mice fed on the HHCy (hyperhomocysteinemia) diet, a diet that induces vascular damage in the brain. She has also carried out NFAT-luciferase reporter gene assays in cultured astrocytes, and confirmed that there is higher NFAT signaling in cytokine-treated astrocytes. Importantly, she and her lab found that an NFAT-specific inhibitor blocked these reporter gene assays, and this was part of an overall characterization of this novel NFAT inhibitor Q134R.
Currently, Susan is working on several projects for the Norris lab. She oversees development and supply of the AAVs for a program project grant and for the Norris lab grants oversees and develops molecular tools including AAVs, adenoviruses, and monoclonal antibodies, carries out experiments related to protein chemistry, including preparation of cell fractions and tissue fractions, analyzes fractions by Western, EMSA, and ELISAs, and does cell culture analysis of cell signaling pathways such as the calcineurin-NFAT pathway and the effects that different pharmacological and molecular agents have on it. She also does IHC (immunohistochemistry) as needed.
One of the most important projects that she is working on is the development of a pair of monoclonal antibodies that detect a “distressed state” of astrocytes. “We have recently gotten a patent for these antibodies, and published a paper for one of them. Our overall goal with them is to determine if they are reliable biomarkers in demented human brain tissue. One of the antibodies clearly labels diseased but not non-demented human brain sections. We are still working up the second antibody. It reacts preferential with 5x mouse brains but we still need to test it on human tissue.”
In addition to these projects, Susan is passionate about the impactful work she does with undergraduates and other team members at Sanders-Brown. She is a valuable contributor to their knowledge and understanding. She has supervised a number of students, including international exchange students from Thailand. She has worked with them on the TBI projects and the monoclonal antibody projects and has gotten good data and publications. She is always happy to see them learn from these experiences and advance in their careers.
Susan enjoys working in the Norris Lab. She appreciates the teamwork and their shared interest in their work. Her team’s desire for Susan to create new things gives her purpose and moves her to fulfill her goals. This collaborative effort helps to make this work rewarding.
A driving force behind Susan’s work has been her family. Susan’s uncle died of cerebral amyloid angiopathy (CAA). This condition is characterized by the buildup of amyloid proteins on the walls of the arteries in the brain, resulting in brain bleeds and dementia. For Susan’s uncle, this was a slow and difficult decline. It was particularly hard on his wife. Susan is hopeful that the work in her lab will lead to better treatments, so that in the future, her relatives and others, will not face cognitive decline. Her contributions to the work of the Norris lab and the work others in the field have done on the calcineurin-NFAT pathway over the past 25 years strongly indicate that blocking this path will help prevent cognitive decline. She is hopeful that calcineurin blockers will be tested in clinical trials in the near future.