Hi! I’m Sriram Amirneni, a junior studying molecular biology and sociology. I am honored to be a recipient of the Chancellor’s Undergraduate Research Fellowship and can’t wait to share my research progress this semester.
The summer before my freshman year, I read an article about researchers at Pitt. They had created mini livers to study diseases. “How cool! I want to work in that lab!” I thought. So, I sent an email to the PI, Dr. Alejandro Soto-Gutierrez, and luckily, he got back to me. For the first few weeks, I went to the lab whenever I had free time and followed the postdocs around. They told me they were working on genetically reprogramming fibroblasts into induced pluripotent stem cells (iPSCs), doing stainings, passaging cells, running qPCRs, and so much more. As I started to become familiar with these techniques, I was given the opportunity to try them out for myself. I started out culturing HEK293, then moved on to HepG2 cells, and eventually AE cells, an established iPSC line. I learned a lot in those first few weeks, just from observation.
As I became more comfortable in the lab, I worked with Dr. Soto-Gutierrez to come up with a project to work on long term. My project is about the genetic disease progressive familial intrahepatic cholestasis (PFIC), which is estimated to affect roughly 1 in 50,000 to 1 in 100,000 live births. It’s an autosomal recessive disease characterized by an impairment in the formation and/or excretion of bile from hepatocytes, the main cells of the liver. Although there are five officially recognized types, and many more associated phenotypes, some symptoms are common between all types. These include cholestasis, jaundice, and pruritus. Pruritus, the intense urge to itch, is one of the most debilitating symptoms. The current medical treatments for PFIC manage the symptoms, ignoring the root cause of the disease, a dysfunctional protein. Liver transplantation is the only curative treatment, but depending on the type of PFIC that the patient has, there may be complicating factors.
Current animal models to study PFIC exhibit a less severe phenotype than the patients do. This is why I am using genetic reprogramming technology to generate patient-specific iPSCs from fibroblasts of real PFIC patients. I am then able to differentiate these iPSCs into human induced hepatocytes to study the function of the mutant protein in vitro. By combining the induced hepatocytes with the other cells of the liver, such as cholangiocytes, we can generate a hepatobiliary system in vitro, allowing us to test the effect of certain drugs on the function of the mutant proteins.
I am very grateful to my mentor, Dr. Soto-Gutierrez, for giving me the opportunity to explore my research interests and grow as a scientist. It turns out the Soto-Gutierrez lab does a lot more than make mini livers! After graduation, I plan on pursuing an MD/PhD program and becoming a physician-scientist. Medical knowledge is based on research and research advances are in the pursuit of generating new treatments or understanding disease processes. In the future, my research will inform my clinical knowledge, and what I am observing in the clinic will give my research additional background. My time in the lab so far has been incredibly rewarding and I am excited for the rest of the semester!
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