Tanja Gonska

Research Synopsis Research Divisions: Cystic Fibrosis and Pancreas diseases My basic science research focuses on evaluating CFTR function, drug response and the role of modifier genes in human epithelial cells and tissues using functional tools. Highly efficient CFTR modulators targeting the basic molecular CF defect have dramatically changed the research and clinical arena in CF. With it, pre-clinical platforms have been established to assess individual responses of these drugs on patient’ own tissue. As a trained electrophysiologist with expertise in human cells and tissue studies, I have successfully implemented high quality Ussing chamber studies in my wet lab to assess CFTR function and drug response on nasal and intestinal tissue/organoids from individualized patients. We are interested in understanding the different in vitro and in vivo responses. Next, we investigate interaction between CFTR and other epithelial channels in airway and intestinal cells. My clinical research focuses on those people who do have disease in CF-associated organs or have been screened positive in CF newborn screening programs, exhibit evidence of CFTR dysfunction, but do not meet the CF diagnostic criteria. We have established cohort studies to examine the natural course of disease/clinical presentation and how it associates with CFTR dysfunction. My clinical research focuses on those people who do have disease in CF-associated organs or have been screened positive in CF newborn screening programs, exhibit evidence of CFTR dysfunction, but do not meet the CF diagnostic criteria. We have established cohort studies to examine the natural course of disease/clinical presentation and how it associates with CFTR dysfunction. As a clinical expert in gastrointestinal complication of CF disease, we are currently also performing clinical studies to understand the association between abdominal pain and intestinal inflammation as well as the effect of highly efficient CFTR modulators. Over the last 10 years I am a collaborative member of the multicentre study design to further our understanding of acute recurrent and chronic pancreatitis to develop a cure in the future (INSPPIRE). Within this consortium my expertise lays within the field of autoimmune pancreatitis (AIP) and acute recurrent and chronic pancreatitis with CFTR dysfunction for whom CFTR modulator drugs could be a therapeutic option. Keywords: Cystic Fibrosis, CFTR function, Ussing chamber studies, CFTR-related disorder, CFSPID, pediatric pancreatic diseases Detailed Description: Electrophysiological studies on human airway and intestinal epithelial cultures as well as use of intestinal organoids to interrogate epithelial function Collaborators: Drs. Theo Moraes, Jim Hu, Christine Bear, Ami Wong, Felix Ratjen, Elizabeth Tullis, Samir Grover, Catharine Streutker, Keith Ooi, Micheal Wilschanski METHODS USED Procedures: Cell cultures, organoids, Ussing chamber studies, immunohistochemistry, Western blot, RT-qPCR EQUIPMENT USED Ussing chamber, Confocal microscope, plate reader, custom-made soft ware PRESENT TRAINEES Malina Barillaro (PhD candidate) Vybhav Gummadi (GI Fellow)

SRA. Birimberg-Schwartz L*, Ip W, Bartlett C, Avolio J, Vonk AM, Gunawardena T, Du K, Esmaeili M, Beekman JM, Rommens J, Strug L, Bear C, Moraes T, Gonska T. Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis. Life Sci Alliance. 2023 Apr 5;6(6):e202201857. doi: 10.26508/lsa.202201857. Print 2023 Jun. PMID: 37024122