Tammy T. Chang, MD, PhD | UCSF Department of Surgery

Biography

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. 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.

Education

1990-1992, California State University, Los Angeles, Early Entrance Program
1992-1994, University of California, Los Angeles, Bachelor of Science, Biology
1994-2003, Harvard Medical School and Harvard Graduate School of Arts and Sciences, M.D., Ph.D. Combined Degree

Residencies

2003-2004 University of California, San Francisco, Surgery, Intern
2004-2009 University of California, San Francisco, Surgery, Resident
2009-2010 University of California, San Francisco, Surgery, Chief Resident

Board Certifications

American Board of Surgery

Collaboration Interests

I am interested in:

physician scientist

Clinical Expertise

Hernia Repair
Complex Abdominal Surgery
Recurrent Hernia
Laparoscopic Inguinal Hernia Repair
Gastrointestinal Cancer
Intra-abdominal Sepsis
Pancreas Surgery
Soft Tissue Infections
Enterocutaneous Fistula

Grants and Funding

The Role of Matrix Rigidity and Hepatocyte Mechanotransduction in Fibrotic Liver Disease | NIH | 2017-07-15 - 2022-06-30 | Role: Principal Investigator
Defining the mechanism of function and engraftment potential of human hepatocyte organoids | American College of Surgeons | 2017-07-01 - 2022-06-30
Liver tissue engineering in space | NSF/CASIS | 2018-09-01 - 2021-08-31 | Role: Principal Investigator
Pioneering regenerative surgery - Mechanisms of cell death and regeneration in liver treated with non-thermal irreversible electroporation (NTIRE) | NIH | 2018-01-01 - 2020-12-31 | Role: Principal Investigator
Using organoids to determine gravity effects on organogenesis and vasculogenesis | NASA | 2018-09-01 - 2020-08-31 | Role: Principal Investigator
Innovating a method of in situ decellularization followed by organoid engraftment | Open Philanthropy Project | 2017-07-01 - 2020-06-30 | Role: PI

Research Narrative

Liver transplantation is currently the only treatment for patients with end-stage liver disease (ESLD), which is the 12th leading cause of death by disease in the U.S. The shortage of donor organs remains a major treatment limitation. Alternatives such as hepatocyte transplantation have shown promise in treating metabolic liver disorders, but low engraftment efficiency and poor long-term efficacy are barriers to broader clinical application.

Another strategy that holds great promise is ex vivo tissue engineering of a functional liver unit that can be implanted and then induced to further expand by host factors after incorporation. Progress towards building three-dimensional (3D) tissue structure with biocompatible scaffolds has been hindered because these materials prevent normal cell-cell and cell-to-extracellular matrix (ECM) interactions.

The slow scaffold degradation rates also prevent remodeling and vascularization of the implant by the local host milieu. Moreover, it is increasingly clear that the surrounding environment is critically important for the durable function of hepatocytes. In particular, evidence shows that three factors independently improve and prolong primary hepatocyte differentiated functions ex vivo: 1) contact with ECM, 2) interaction with stromal cells (fibroblasts and endothelium), and 3) 3D cell-cell contact.

Dr. Chang's previous work showed that hepatocytes cultured in solid-body rotational bioreactors, which provide minimal shear stress with maximal 3D spatial freedom, produced self-aggregated spheroids with optimal metabolic and synthetic gene expression and function as compared to those cultured in two-dimensional (2D) monolayers.

Research in the The Chang Laboratory for Liver Tissue Engineering builds upon those observations and aims to generate "micro-liver-tissues" with endogenous ECM scaffolds and built-in microvascular networks through co-culture of hepatocytes with stromal cells within solid-body rotational bioreactors. Findings from this research are expected advance the field of tissue engineering by increasing our understanding of hepatocyte cellular response to matrix composition and heterotypic 3D cell contact. It will form the basis for the long-term goal of creating ex vivo engineered liver tissue for therapeutic implantation in patients with ESLD.

Research Interests

Liver Tissue Engineering

Publications

MOST RECENT PUBLICATIONS FROM A TOTAL OF 36

The effect of vibration and acceleration on the stability of isochoric (constant volume) supercooled aqueous systems.
Sheps N, Consiglio AN, Ouyang Y, Chang TT, Rubinsky B| 2026-01-13 | PubMed
Hepatocyte Rho-associated kinase signaling is required for mice to survive experimental porphyria-associated liver injury.
Herrera JM, Weng Y, Lieberthal TJ, Paoletti M, Chang TT| 2025-01-29 | PubMed
Metastatic melanoma to small bowel: metastasectomy is supported in the era of immunotherapy and checkpoint inhibitors.
Wong P, Wisneski AD, Tsai KK, Chang TT, Hirose K, Nakakura EK, Daud AI, Maker AV, Corvera CU| 2024-03-11 | PubMed
Irreversible Electroporation of the Liver Increases the Transplant Engraftment of Hepatocytes.
Han S, Dicker ML, Lopez-Ichikawa M, Vu NK, Rubinsky B, Chang TT| 2023-09-20 | PubMed
Isochoric Supercooling Organ Preservation System.
Nastase G, Botea F, Be?chea GA, Câmpean ?I, Barcu A, Neac?u I, Herlea V, Popescu I, Chang TT, Rubinsky B, ?erban A| 2023-08-07 | PubMed
An exploratory study on isochoric supercooling preservation of the pig liver.
Botea F, Nastase G, Herlea V, Chang TT, ?erban A, Barcu A, Rubinsky B, Popescu I| 2023-05-16 | PubMed
Self-Assembled Matrigel-Free iPSC-Derived Liver Organoids Demonstrate Wide-Ranging Highly Differentiated Liver Functions.
Weng Y, Han S, Sekyi MT, Su T, Mattis AN, Chang TT| 2023-03-02 | PubMed
Pancreatic islets implanted in an irreversible electroporation generated extracellular matrix in the liver.
Zhang Y, Lv Y, Wang Y, Chang TT, Rubinsky B| 2023-01-19 | PubMed
Self-assembled Matrigel-free iPSC-derived liver organoids demonstrate wide-ranging highly-differentiated liver functions
Yun Weng, Simon Han, Maria T Sekyi, Tao Su, Aras N Mattis, Tammy T Chang| 2022-12-27 | UCSF Research Profile
Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice.
Lopez-Ichikawa M, Vu NK, Nijagal A, Rubinsky B, Chang TT| 2021-07-22 | PubMed
Focal adhesion kinase (FAK) promotes cholangiocarcinoma development and progression via YAP activation.
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| 2021-05-28 | PubMed
Jejunal prolapse and incarceration following feeding tube exchange.
Conroy PC, Colley A, Bongiovanni T, Chang TT, Harris H| 2020-12-01 | PubMed
Liver epithelial focal adhesion kinase modulates fibrogenesis and hedgehog signaling.
Weng Y, Lieberthal TJ, Zhou VX, Lopez-Ichikawa M, Armas-Phan M, Bond TK, Yoshida MC, Choi WT, Chang TT| 2020-10-15 | PubMed
Intra-Vital Imaging Demonstrates Robust Recruitment of Neutrophils after Irreversible Electroporation Tissue Ablation.
Maya A. Lopez-Ichikawa, Tammy T. Chang| 2019-10-01 | UCSF Research Profile
Normal and fibrotic liver parenchyma respond differently to irreversible electroporation.
Lyu C, Lopez-Ichikawa M, Rubinsky B, Chang TT| 2019-03-14 | PubMed
Liver Fibrosis: Current Approaches and Future Directions for Diagnosis and Treatment.
Jennifer Y. Chen, Dhruv Thakar, Tammy T. Chang| 2019-01-01 | UCSF Research Profile
Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver.
Zhang Y, Lyu C, Liu Y, Lv Y, Chang TT, Rubinsky B| 2018-06-07 | PubMed
Using non-thermal irreversible electroporation to create an in vivo niche for exogenous cell engraftment.
Chang TT, Zhou VX, Rubinsky B| 2017-05-01 | PubMed
Reply.
Chang TT| 2017-03-30 | PubMed
Direct orthotopic implantation of hepatic organoids.
Zhou VX, Lolas M, Chang TT| 2016-12-29 | PubMed
Force-dependent breaching of the basement membrane.
Chang TT, Thakar D, Weaver VM| 2016-12-23 | PubMed
Hepatic Focal Adhesion Kinase Signaling Modulates Development of Liver Fibrosis.
Tammy T. Chang, Vivian X. Zhou| 2016-10-01 | UCSF Research Profile
Gastrointestinal Zygomycosis Masquerading as Acute Appendicitis.
Choi WT, Chang TT, Gill RM| 2016-05-19 | PubMed
Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.
Desai SS, Tung JC, Zhou VX, Grenert JP, Malato Y, Rezvani M, Español-Suñer R, Willenbring H, Weaver VM, Chang TT| 2016-03-09 | PubMed
Spaceflight alters expression of microRNA during T-cell activation.
Hughes-Fulford M, Chang TT, Martinez EM, Li CF| 2015-08-14 | PubMed
Spaceflight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines.
Chang TT, Spurlock SM, Candelario TL, Grenon SM, Hughes-Fulford M| 2015-06-17 | PubMed
Molecular mechanisms underlying the enhanced functions of three-dimensional hepatocyte aggregates.
Chang TT, Hughes-Fulford M| 2013-12-12 | PubMed
The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity.
Chang TT, Walther I, Li CF, Boonyaratanakornkit J, Galleri G, Meloni MA, Pippia P, Cogoli A, Hughes-Fulford M| 2012-07-02 | PubMed
Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line cells demonstrate distinct global gene expression patterns and functional phenotypes.
Chang TT, Hughes-Fulford M| 2009-03-01 | PubMed
Caudate split for open and laparoscopic liver resections.
Chang TT, Corvera CU| 2008-12-01 | PubMed
Implementation of a multidisciplinary treatment team for hepatocellular cancer at a Veterans Affairs Medical Center improves survival.
Chang TT, Sawhney R, Monto A, Davoren JB, Kirkland JG, Stewart L, Corvera CU| 2008-01-01 | PubMed
Injury in the elderly and end-of-life decisions.
Chang TT, Schecter WP| 2007-02-01 | PubMed
Recovery from EAE is associated with decreased survival of encephalitogenic T cells in the CNS of B7-1/B7-2-deficient mice.
Chang TT, Sobel RA, Wei T, Ransohoff RM, Kuchroo VK, Sharpe AH| 2003-07-01 | PubMed
Genetic background determines the requirement for B7 costimulation in induction of autoimmunity.
Jabs C, Greve B, Chang TT, Sobel RA, Sharpe AH, Kuchroo VK| 2002-09-01 | PubMed
Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity.
Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, Berry G, DeKruyff RH, Umetsu DT| 2002-07-29 | PubMed
Role of the B7-CD28/CTLA-4 pathway in autoimmune disease.
Chang TT, Kuchroo VK, Sharpe AH| 2002-01-01 | PubMed

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