Kari N. Nejak-Bowen, MBA, PhD
Assistant Professor of Pathology

Dr. Nejak-Bowen
Dr. Nejak-Bowen is a member of the Division of Experimental Pathology.

Office Location:
University of Pittsburgh
Department of Pathology
200 Lothrop St, Room S-433
Pittsburgh, PA 15261

Contact Information:
Office Telephone: 412-624-3354
Lab Telephone: 412-383-7820
Fax: 412-648-1916
Email: knnst5@pitt.edu

Education

  • BS - 1999, University of Pittsburgh
  • MBA - 2002, University of Pittsburgh
  • PhD - 2010, University of Pittsburgh

Specialties

Cellular and Molecular Pathology, Molecular Biology, Liver Pathobiology

Awards and Honors

  • Pathology Postdoctoral Research Training Program (PPRTP) Award, 2011-2012
  • American Liver Foundation & American Association of Study of Liver Diseases (AASLD) Postdoctoral Fellow Award, 2012-2013
  • Recipient of American Society of Investigative Pathology Young Scientist Leadership Award, 2014

Research Interests

Kari Nejak-Bowen is an Assistant Professor in the Experimental Pathology Division at the University of Pittsburgh, School of Medicine. She graduated summa cum laude with a BS in Microbiology from the University of Pittsburgh and then went on to earn an MBA, also from the University of Pittsburgh. Kari performed her graduate work at the University of Pittsburgh as well. Under the mentorship of Dr. Paul Monga, she studied the role of Wnt/ β-catenin signaling in liver regeneration and injury. During her graduate career she received several awards, including the Experimental Pathologist-in-Graduate Training Merit Award from ASIP. After graduating with honors in 2010, she did a postdoctoral fellowship with Dr. George Michalopoulos, where she studied the role of hepatocyte growth factor in liver regeneration, and then with Dr. Monga, where she studied the regulation of cyclin D1 during liver regeneration. During her postdoctoral training, she was the recipient of a University of Pittsburgh Pathology Postdoctoral Research Training Grant and an American Liver Foundation Postdoctoral Fellowship Award. Kari received her first R01 in 2014 as a Research Assistant Professor. She has published around 20 manuscripts, including several senior-author publications, contributed other scholarly works (reviews and book chapters) in the area of her research, and delivered numerous presentations at national and international meetings. She has also contributed towards teaching in the Cellular and Molecular Pathology graduate program and has been co-Director of the Stem Cells graduate course for several years.

For the past 11 years, her research has been focused on understanding the cellular and molecular basis of liver health and disease. Specifically, she is interested in understanding the role of signaling pathways such as Wnt/ β-catenin in liver inflammation, injury, and cholestasis. She has identified novel downstream targets of β-catenin in the liver such as regucalcin. She has also demonstrated the advantage of activating β-catenin signaling to enhance liver regeneration. She characterized an inhibitory interaction between β-catenin and the p65 subunit of NF- B. More recently, she developed a significant interest in cholestatic liver disease, and has made several novel and important findings using models of bile duct injury and cholestasis. First, lack of β-catenin in hepatocytes led to lesser liver injury, fibrosis, and atypical ductular proliferation, as well as decreased total hepatic bile acids and enhanced farnesoid X receptor activation after bile duct ligation (BDL). She recently identified a novel association of β-catenin with FXR that is unresponsive to bile acids or FXR agonists but sensitive to β-catenin inhibition, which causes synergistic activation of FXR in combination with an FXR agonist. Secondly, she is elucidating the role of β-catenin in transdifferentiation of hepatocytes to cholangiocytes during chronic biliary injury, such as 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) diet. Her lab recently identified an upregulation of Wnt signaling after DDC and BDL, and that cholangiocyte markers are absent in hepatocytes of mice lacking Wnt signaling, which coincides with a decrease in survival. Conversely, transgenic mice expressing a S45-mutated non-degradable form of β-catenin in liver (TG) have a significant number of hepatocytes expressing cholangiocyte markers after exposure to DDC diet compared to wild-types (WT). These observations suggest a novel preclinical opportunity to treat intrahepatic cholestasis by stimulating hepatocyte transdifferentiation through activation of Wnt/ β-catenin. Her long-term goal is to ultimately apply her knowledge to the development of improved diagnostics and clinically relevant therapies in the treatment of cholestatic liver disease, particularly to primary sclerosing cholangitis, a condition with a significant unmet clinical need.

NIH Research

View Dr. Nejak-Bowen's NIH RePORT on nih.gov

Selected Publications

View Dr. Nejak-Bowen's publications on PubMed

  • Dual catenin loss in murine liver causes tight junctional deregulation and progressive intrahepatic cholestasis. Pradhan-Sundd T, Zhou L, Vats R, Jiang A, Molina L, Singh S, Poddar M, Russell JM, Stolz DB, Oertel M, Apte U, Watkins S, Ranganathan S, Nejak-Bowen KN, Sundd P, Monga SP. Hepatology. 2018 Jun;67(6):2320-2337.
  • Thompson MD, Moghe A, Cornuet P, Marino R, Tian J, Wang P, Ma X, Abrams M, Locker J, Monga SPS, Nejak-Bowen K. β-catenin regulation of farnesoid X receptor signaling and bile acid metabolism during murine cholestasis. Hepatology. 2018 Mar;67(3):955-971.
  • Nejak-Bowen K, Moghe A, Cornuet P, Preziosi M, Nagarajan S, Monga SP. Role and regulation of p65/β-catenin association during liver injury and regeneration: a 'complex' relationship. Gene Expr. 2017 Apr 28.
  • Okabe H, Yang J, Sylakowski K, Yovchev M, Miyagawa Y, Nagarajan S, Chikina M, Oertel M, Baba H, Monga SP, Nejak-Bowen KN. Wnt signaling regulates hepatobiliary repair following cholestatic liver injury in mice. Hepatology. 2016 Nov;64(5):1652-1666.
  • Alvarado TF, Puliga E, Preziosi M, Poddar M, Singh S, Columbano A, Nejak-Bowen K, Monga SP. Thyroid Hormone Receptor-β Agonist Induces β-catenin-Dependent Hepatocyte Proliferation in Mice: Implications in Hepatic Regeneration. Gene Expr. 2016 May 24.
  • 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 β-catenin Are Prone to Cholestatic Injury and Chemical Carcinogenesis. Am J Pathol. 2015 Dec;185(12):3274-89.
  • Yang J, Cusimano A, Monga JK, Preziosi ME, Pullara F, Calero G, Lang R, Yamaguchi TP, Nejak-Bowen KN, Monga SP. WNT5A Inhibits Hepatocyte Proliferation and Concludes β-catenin Signaling in Liver Regeneration. Am J Pathol. 2015 Aug;185(8):2194-205.
  • Delgado A, Okabe H, Preziosi M, Russell JO, Alvarado TF, Oertel M, Nejak-Bowen KN, Zhang Y, Monga SP. Complete response of Ctnnb1-mutated tumors to β-catenin suppression by locked nucleic antisense in mouse hepatocarcinogenesis model. Journal of Hepatology. Accepted October 2014 (In Press).
  • Yang J, Mowry LE, Nejak-Bowen KN, Okabe H, Diegel CR, Lang RA, Williams BO, Monga SP. Beta-catenin signaling in murine liver zonation and regeneration: A Wnt-Wnt situation! Hepatology. 2014 Feb 20. doi: 10.1002/hep.27082. [Epub ahead of print]
  • Lee JM, Yang J, Newell P, Singh S, Parwani A, Friedman SL, Nejak-Bowen KN, Monga SP. β-catenin signaling in hepatocellular cancer: Implications in inflammation, fibrosis, and proliferation. Cancer Lett. 2013 Sep 23.
  • Nejak-Bowen KN, Monga SP. Wnt drives Stem cell-mediated repair response after hepatic injury. Hepatology 2013. 2013 Jun 20.
  • Nejak-Bowen K, Orr A, Bowen WC Jr, Michalopoulos GK. Gliotoxin-induced changes in rat liver regeneration after partial hepatectomy. Liver Int. 2013 Aug;33(7):1044-55.
  • Awuah PK, Nejak-Bowen KN, Monga SP. Role and Regulation of PDGFRα Signaling in Liver Development and Regeneration. Am J Pathol. 2013 May;182(5):1648-58.
  • Nejak-Bowen K, Orr A, Bowen WC Jr, Michalopoulos GK. Conditional genetic elimination of hepatocyte growth factor in mice compromises liver regeneration after partial hepatectomy. PLoS One. 2013;8(3):e59836. Epub 2013 Mar 20.
  • Nejak-Bowen K, Kikuchi A, Monga SP. β-catenin-NF-κB interactions in murine hepatocytes: A complex to die for. Hepatology. 2013 Feb;57(2):763-74.
  • Thompson M, Nejak-Bowen K, and Monga SPS. "Crosstalk of the Wnt signaling pathway". Targeting the Wnt pathway in cancer. 1st ed. Ed. Angus W. Thomson and Michael T. Lotze. Springer, 2011.
  • Nejak-Bowen KN, Monga SP. β-catenin signaling, liver regeneration and hepatocellular cancer: Sorting the good from the bad. Semin Cancer Biol. 2010 Dec 21.
  • Nejak-Bowen KN, Thompson MD, Singh S, Bowen WC Jr, Dar MJ, Khillan J, Dai C, Monga SP. Accelerated liver regeneration and hepatocarcinogenesis in mice overexpressing serine-45 mutant β-catenin. Hepatology. 2010 May;51(5):1603-13.
  • Nejak-Bowen KN, Zeng G, Tan X, Cieply B, Monga SP. β-catenin regulates vitamin C biosynthesis and cell survival in murine liver. J Biol Chem. 2009 Oct 9;284(41):28115-27.
  • Nejak-Bowen K and Monga SPS. Wnt/β-catenin signaling in hepatic organogenesis. Organogenesis. 2008 4(2): 92-99.