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.

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)

Recent Publications

SRA. Birimberg-Schwartz L*, Ip W, BartlettC, AvolioJ, VonkAM, GunawardenaT, DuK, EsmaeiliM, BeekmanJM, RommensJ, StrugL, Bear C, Moraes T, GonskaT. 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 

Gould MJ*, Smith H, Rayment JH, Machilda H, Gonska T, Galante GJ*.  CFTR modulators increase risk of acute pancreatitis in pancreatic insufficient patients with cystic fibrosis. Journal of Cystic Fibrosis. 2022 Jul;21(4):600-602.

Gonska T, Keenan K, Au J, Dupuis A, Chilvers MA, Burgess C, Bjornson C, Fairservice L, Brusky J, Kherani T, Jober A, Kosteniuk L, Price A, Itterman J, Morgan L, Mateos-Corral D, Hughes D, Donnelly C, Smith MJ, Iqbal S, Arpin J, Reisman J, Hammel J, van Wylick R, Derynck M, Henderson N, Solomon M, Ratjen F.  Outcomes of Cystic Fibrosis Screening-Positive Infants with Inconclusive Diagnosis at School Age. Pediatrics. 2021 Dec 1;148(6):e2021051740.

Birimberg-Schwartz L*, Rajiwate S, Dupuis A, Gonska T. Pediatric Acute Pancreatitis: Changes in Management and Disease Outcomes Over 16 Years. Pancreas. 2021 Mar 1;50(3):341-346.

Laselva O, Bartlett C, Gunawardena TNA, Ouyang H, Eckford PDW, Moraes TJ, Bear CE, Gonska T. Rescue of multiple class II CFTR mutations by elexacaftor+ tezacaftor+ivacaftor mediated in part by the dual activities of Elexacaftor as both corrector and potentiator. European Respiratory Journal - European Respiratory Society. 2021 Jun 17;57(6):2002774.

ScheersI*, ChavhanGB, ChamiR, Carman N, ScainiV, GaisanoH, MarconM, Gonska T.  Clinical Characteristics and Long-term Outcomes of Children with Fibrosing Pancreatitis.  J Pediatr Gastroenterol Nutr 2020 Jun;70(6):801-807. PMID: 32443035

Ahmadi S, Wu YS, Li M, Ip W, Lloyd-Kuzik A*, Di Paola M, Du K, Xia S, Lew A, Bozoky Z, Forman-Kay J, Bear CE, Gonska T. Augmentation of CFTR function in human bronchial epithelial cells via SLC6A14-dependent amino acid uptake: Implications for treatment of Cystic Fibrosis. Am J Respir Cell Mol Biol. 2019 Dec;61(6):755-764 PMID:31189070  

Appointments

Primary: Department of Pediatrics, University of Toronto, the Hospital for Sick Children

Associate Professor and Senior Associate Scientist

Division of Gastroenterology, Hepatology and Nutrition

Program of Translational Research 

The Hospital for Sick Children

Cross-Appointment to Physiology

Cross-Appointment to Institute of Medical Science

Cross-Appointment to St. Michael’s Hospital