Tammy T. Chang, MD, PhD
Associate Professor
Surgery
School of Medicine
Tissue engineering and regeneration are the next evolutionary step in surgical practice. Today, surgeons resect, reconstruct, and transplant to treat a diverse array of diseases. In the near future, our armamentarium will increase to include using our surgical skills to induce tissue regeneration in situ or to implant ex vivo engineered organs.
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Accelerating advances in biotechnology, stem cell biology, and minimally invasive surgery are ripe for convergence, which will lead to the creation of novel surgical treatments to replace diseased or dysfunctional tissues. Our lab's goal is to make significant contributions to bringing these regenerative surgical therapies from the lab into the operating room.
In order to translate regenerative surgery from concept to therapeutic reality, our lab focuses on a complex and vital solid organ, the liver, for several reasons. First, there is great clinical need to develop alternative therapies for end stage liver disease, which is currently treated by liver transplantation and severely limited by the shortage of donor organs. Second, the liver has enormous innate capacity to regenerate in response to injury and metabolic demand, a feature that can be exploited to facilitate development of regenerative surgical approaches. Finally, building a solid organ such as the liver ex vivo remains the most challenging goal in tissue engineering and a problem of sufficient difficulty that is worthy of intense focus.
Our lab has 3 major areas of investigation aimed at advancing the field of liver tissue engineering:
1) Understanding the role of the physical environment and mechano-signal transduction in regulating hepatocyte function in healthy and diseased liver. 2) Elucidating the importance of dimensionality in promoting the generation of highly-functional human stem cell-derived liver organoids. 3) Developing surgical strategies for efficient orthotopic engraftment of hepatocytes and hepatic organoids into the liver.
Websites
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- Department of Surgery Profile (surgery.ucsf.edu)
- OpenAccess articles (escholarship.org)
- The Chang Laboratory for Liver Tissue Engineering (livertissueengineering.ucsf.edu)
Grants and Projects
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- The Role of Matrix Rigidity and Hepatocyte Mechanotransduction in Fibrotic Liver Disease, NIH, 2017-2022
- Defining the mechanism of function and engraftment potential of human hepatocyte organoids, American College of Surgeons, 2017-2022
- Liver tissue engineering in space, NSF/CASIS, 2018-2021
- Pioneering regenerative surgery - Mechanisms of cell death and regeneration in liver treated with non-thermal irreversible electroporation (NTIRE), NIH, 2018-2020
- Using organoids to determine gravity effects on organogenesis and vasculogenesis, NASA, 2018-2020
- Innovating a method of in situ decellularization followed by organoid engraftment, Open Philanthropy Project, 2017-2020
Publications (34)
Top publication keywords:
Focal Adhesion Kinase 1Hepatocyte Nuclear Factor 4Cell TransplantationBasement MembraneHepatocytesSmoothened ReceptorOrganoidsLiver CirrhosisLiverExtracellular MatrixB7-1 AntigenSpace FlightElectroporationGenes, Immediate-EarlyLiver Regeneration
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Self-Assembled Matrigel-Free iPSC-Derived Liver Organoids Demonstrate Wide-Ranging Highly Differentiated Liver Functions.
Stem cells (Dayton, Ohio) 2023 Weng Y, Han S, Sekyi MT, Su T, Mattis AN, Chang TT -
Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice.
Scientific reports 2021 Lopez-Ichikawa M, Vu NK, Nijagal A, Rubinsky B, Chang TT -
Liver epithelial focal adhesion kinase modulates fibrogenesis and hedgehog signaling.
JCI insight 2020 Weng Y, Lieberthal TJ, Zhou VX, Lopez-Ichikawa M, Armas-Phan M, Bond TK, Yoshida MC, Choi WT, Chang TT -
Normal and fibrotic liver parenchyma respond differently to irreversible electroporation.
HPB : the official journal of the International Hepato Pancreato Biliary Association 2019 Lyu C, Lopez-Ichikawa M, Rubinsky B, Chang TT -
Using non-thermal irreversible electroporation to create an in vivo niche for exogenous cell engraftment.
BioTechniques 2017 Chang TT, Zhou VX, Rubinsky B -
Direct orthotopic implantation of hepatic organoids.
The Journal of surgical research 2016 Zhou VX, Lolas M, Chang TT -
Spaceflight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2015 Chang TT, Spurlock SM, Candelario TL, Grenon SM, Hughes-Fulford M -
Molecular mechanisms underlying the enhanced functions of three-dimensional hepatocyte aggregates.
Biomaterials 2013 Chang TT, Hughes-Fulford M
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Metastatic melanoma to small bowel: metastasectomy is supported in the era of immunotherapy and checkpoint inhibitors.
World journal of surgical oncology 2024 Wong P, Wisneski AD, Tsai KK, Chang TT, Hirose K, Nakakura EK, Daud AI, Maker AV, Corvera CU -
Irreversible Electroporation of the Liver Increases the Transplant Engraftment of Hepatocytes.
The Journal of surgical research 2023 Han S, Dicker ML, Lopez-Ichikawa M, Vu NK, Rubinsky B, Chang TT -
Isochoric Supercooling Organ Preservation System.
Bioengineering (Basel, Switzerland) 2023 Nastase G, Botea F, Be?chea GA, Câmpean ?I, Barcu A, Neac?u I, Herlea V, Popescu I, Chang TT, Rubinsky B, ?erban A -
An exploratory study on isochoric supercooling preservation of the pig liver.
Biochemistry and biophysics reports 2023 Botea F, Nastase G, Herlea V, Chang TT, ?erban A, Barcu A, Rubinsky B, Popescu I -
Pancreatic islets implanted in an irreversible electroporation generated extracellular matrix in the liver.
Radiology and oncology 2023 Zhang Y, Lv Y, Wang Y, Chang TT, Rubinsky B -
Self-assembled Matrigel-free iPSC-derived liver organoids demonstrate wide-ranging highly-differentiated liver functions
Stem Cells 2022 Yun Weng, Simon Han, Maria T Sekyi, Tao Su, Aras N Mattis, Tammy T Chang -
Focal adhesion kinase (FAK) promotes cholangiocarcinoma development and progression via YAP activation.
Journal of hepatology 2021 Song X, Xu H, Wang P, Wang J, Affo S, Wang H, Xu M, Liang B, Che L, Qiu W, Schwabe RF, Chang TT, Vogl M, Pes GM, Ribback S, Evert M, Chen X, Calvisi DF -
Jejunal prolapse and incarceration following feeding tube exchange.
The journal of trauma and acute care surgery 2020 Conroy PC, Colley A, Bongiovanni T, Chang TT, Harris H -
Intra-Vital Imaging Demonstrates Robust Recruitment of Neutrophils after Irreversible Electroporation Tissue Ablation.
Journal of the American College of Surgeons 2019 Maya A. Lopez-Ichikawa, Tammy T. Chang -
Liver Fibrosis: Current Approaches and Future Directions for Diagnosis and Treatment.
Fibrosis in Disease 2019 Jennifer Y. Chen, Dhruv Thakar, Tammy T. Chang -
Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver.
Biochemical and biophysical research communications 2018 Zhang Y, Lyu C, Liu Y, Lv Y, Chang TT, Rubinsky B -
Reply.
Hepatology (Baltimore, Md.) 2017 Chang TT -
Force-dependent breaching of the basement membrane.
Matrix biology : journal of the International Society for Matrix Biology 2016 Chang TT, Thakar D, Weaver VM -
Hepatic Focal Adhesion Kinase Signaling Modulates Development of Liver Fibrosis.
Journal of the American College of Surgeons 2016 Tammy T. Chang, Vivian X. Zhou -
Gastrointestinal Zygomycosis Masquerading as Acute Appendicitis.
Case reports in gastroenterology 2016 Choi WT, Chang TT, Gill RM -
Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.
Hepatology (Baltimore, Md.) 2016 Desai SS, Tung JC, Zhou VX, Grenert JP, Malato Y, Rezvani M, Español-Suñer R, Willenbring H, Weaver VM, Chang TT -
Spaceflight alters expression of microRNA during T-cell activation.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2015 Hughes-Fulford M, Chang TT, Martinez EM, Li CF -
The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity.
Journal of leukocyte biology 2012 Chang TT, Walther I, Li CF, Boonyaratanakornkit J, Galleri G, Meloni MA, Pippia P, Cogoli A, Hughes-Fulford M -
Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line cells demonstrate distinct global gene expression patterns and functional phenotypes.
Tissue engineering. Part A 2009 Chang TT, Hughes-Fulford M -
Caudate split for open and laparoscopic liver resections.
Journal of the American College of Surgeons 2008 Chang TT, Corvera CU -
Implementation of a multidisciplinary treatment team for hepatocellular cancer at a Veterans Affairs Medical Center improves survival.
HPB : the official journal of the International Hepato Pancreato Biliary Association 2008 Chang TT, Sawhney R, Monto A, Davoren JB, Kirkland JG, Stewart L, Corvera CU -
Injury in the elderly and end-of-life decisions.
The Surgical clinics of North America 2007 Chang TT, Schecter WP -
Recovery from EAE is associated with decreased survival of encephalitogenic T cells in the CNS of B7-1/B7-2-deficient mice.
European journal of immunology 2003 Chang TT, Sobel RA, Wei T, Ransohoff RM, Kuchroo VK, Sharpe AH -
Genetic background determines the requirement for B7 costimulation in induction of autoimmunity.
European journal of immunology 2002 Jabs C, Greve B, Chang TT, Sobel RA, Sharpe AH, Kuchroo VK -
Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity.
Nature medicine 2002 Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, Berry G, DeKruyff RH, Umetsu DT -
Role of the B7-CD28/CTLA-4 pathway in autoimmune disease.
Current directions in autoimmunity 2002 Chang TT, Kuchroo VK, Sharpe AH