Tirthadipa Pradhan-Sundd, PhD
Instructor of Pathology

Dr. Bell
Dr. Pradhan-Sundd is a member of the Division of Experimental Pathology.

Office Location:
University of Pittsburgh
Department of Pathology
200 Lothrop St, Room S-420
Pittsburgh, PA 15261

Contact Information:
Telephone:412-624-3354
Fax: 412-648-1916
Email: tip9@pitt.edu

Education

  • MPhil - University of Sheffield, UK, 2011
  • PhD - Simon Fraser University (mentor: Dr. Esther Verheyen), Canada, 2015
  • Postdoctoral fellowship - University of Pittsburgh, (mentor: Dr. Paul Monga), USA, 2018

Research Interests

  • Identifying molecular targets of Sickle cell Hepatic crisis: Sickle cell disease (SCD) is an autosomal recessive genetic disorder that affects ~100,000 Americans and millions of people worldwide. Sickle cell anemia can affect any part of the body and one of the main organs to be affected is the hepatobiliary system. I have used a transgenic, humanized mice model of SCD that exclusively expresses sickle human hemoglobin. Preliminary data reveal that SCD mice developed liver injury and cholestasis. Using our recently developed real-time in vivo imaging of blood and bile transport, we identified sinusoidal ischemia, impairment of canalicular bile secretion, and intrahepatic accumulation of bile acids in SCD but not control mice. Understanding the molecular events that initiate and promulgate sickle cell induced cholestasis has great potential to prevent hepatic insult and progressive liver damage in SCD. These studies are currently in progress and my role is of principal investigator.

  • Understanding chronic liver injury through advanced multiphoton intravital imaging: Liver fibrosis, hepatocellular necrosis, inflammation and proliferation of liver progenitor cells are the hallmark of chronic liver injury. Several murine models have been used to mimic the end-stage pathophysiology of chronic liver injury. However, the underlying differences in the molecular mechanism driving liver injury in different models remains largely unknown due to our inability to visualize the progression of liver injury in vivo in mice. We have introduced quantitative Liver Intravital Microscopy (qLIM) (in collaboration with Dr. Prithu Sundd) that enables real-time assessment of bile transport and blood-bile barrier (BBlB) integrity in the intact liver of live mice (Pradhan-Sundd et al., Hepatology, 2017, Gastroenterology, 2018). Using qLIM, we showed for the first time that breach of BBlB and impairment of bile secretion promotes choline-deficient, ethionine-supplemented (CDE) and 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) diets induced chronic liver injury in mice. qLIM revealed that impairment in bile secretion is associated with the disruption of the BBlB and differential expression of several tight junction (TJ) proteins and bile transporters. We will continue using this imaging method to elucidate injury initiation, progression, and recovery processes in other models of chronic liver injury.

  • Molecular mechanisms of the blood bile barrier formation and its role in hepatopathophysiology: Epithelial barriers are indispensable to life. These barriers function to exclude macromolecules from the epithelia, promotes host defense against microorganisms and protects from injury and inflammation. A relatively less studied barrier is the blood bile barrier (BBlB) present in liver which restricts the mixing of blood with bile.Integrity of the blood-bile barrier (BBlB) in the liver is central to the secretion and travel of bile. Loss of BBlB function has been shown to be the primary pathophysiology behind cholestasis in children as well as adults. However, the cellular and molecular mechanism that promulgates BBlB failure is incompletely understood. Using advanced imaging technique, biochemistry and genetics, I am characterizing the role and regulation of BBlB in heptopathophysiology. I showed for the first time the role of adherens junction protein ? and ?-catenin in BBlB maintenance. This study, which was published in Hepatology was my first primary author manuscript during my postdoctoral training. Subsequently, I have characterized the role of BBlB in diet induced chronic liver injury models which is published in Gastroenterology. I am also characterizing the role of BBlB in promoting hepatocyte polarity.

Selected Publications

View Pradhan-Sundd's publications on PubMed

  • Pradhan-Sundd, T. Vats, R. Russell, J, Monga S.P and Sundd, P Dysregulated tight junctional proteins and bile transporters enables chronic liver injury. Gastroenterology. 2018 Jun 28. pii: S0016-5085(18)34690-0. doi: 10.1053/j.gastro.2018.06.048. [Epub ahead of print]
  • Pradhan-Sundd, T. Zhou L, Vats, R. Molina L, Singh S, Watkins S, Sundd, P and Monga S.P., Dual beta-catenin and gamma-catenin loss disrupts hepatic tissue barrier to cause cholestatic liver disease. Hepatology. 2017 Oct 10. doi: 10.1002/hep.29585.
  • Zhou L, Pradhan-Sundd, T. Poddar M, Singh S, Kikuchi A, Stolz DB, Shou W, Li Z, Nejak-Bowen KN, Monga SP. Mice with Hepatic Loss of the Desmosomal Protein ?-Catenin Are Prone to Cholestatic Injury and Chemical Carcinogenesis. Am J Pathol. 2015 Dec; 185(12):3274-89.
  • Kikuchi A, Pradhan-Sundd, T. Singh S, Nagarajan S, Loizos N, Monga S. Platelet-Derived Growth Factor Receptor ? Contributes to Human Hepatic Stellate Cell Proliferation and Migration. Am J Pathol. 2017 Jul 20. pii: S0002-9440(17)30329-2
  • Ma L, Umasankar PK, Wrobel AG, Lymar A, McCoy AJ, Holkar SS, Jha A, Pradhan-Sundd, T. Watkins SC, Owen DJ, Traub LM. Transient Fcho1/2?Eps15/R?AP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding. Dev Cell. 2016 Jun 6; 37(5):428-43.
  • Puliga E, Min Q, Tao J, Zhang R, Pradhan-Sundd T, Poddar M, Singh S, Columbano A, Yu J, Monga SP. Thyroid hormone receptor-beta agonist GC-1 inhibits Met-?-catenin driven hepatocellular cancer. Am J Pathol. 2017 Aug 11. pii: S0002-9440(17)30403-0.
  • Molina L, Bell D, Tao J, Preziosi M, Pradhan-Sundd T, Singh S, Poddar M, Luo J, Ranganathan S, Chikina M, Monga SP. Hepatocyte-derived lipocalin 2 is a potential serum biomarker reflecting tumor burden in hepatoblastoma. Am J Pathol. 2018 Jun 16. pii: S0002-9440(17)31236-1. doi: 10.1016/j.ajpath.2018.05.006. [Epub ahead of print]