Tammy T. Chang, M.D., Ph.D.
- Associate Professor of Surgery
- Division of General Surgery
Contact Information
521 Parnassus Ave., C341
San Francisco, CA 94143-0790
Tel: (415) 476-0762
Fax: (415) 476-8694
[email protected]
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
Fellowships
- 2006-2008 University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, Liver Tissue Engineering, American College of Surgeons Research Scholarship, Research Fellow
- 2010-2011 University of California, San Francisco, Minimally Invasive Surgery and Bariatric Surgery, Clinical Fellow
Biography
Tammy T. Chang, M.D., Ph.D. is a gastrointestinal and acute care surgeon in the Division of General Surgery.
Her clinical training includes internship, residency, and chief residency in Surgery at the University of California, San Francisco. In addition, she has completed a clinical fellowship in Minimally Invasive Surgery and Bariatric Surgery at the same institution. Her research experience includes a post-doctoral fellowship investigating three-dimensional (3D) organization of hepatocytes in rotational bioreactors funded by the American College of Surgeons Research Scholarship.
Her background demonstrates her strong commitment to facilitate transfer of advances in laboratory research into clinical applications that benefit patients. Dr. Chang holds an M.D., Ph.D. combined degree from Harvard Medical School through the Medical Scientist Training Program. Her Ph.D. degree is in the field of immunology with specific focus on immunoregulation in autoimmune disease.
Her research includes the study of 3D hepatocyte culture with long-term goals of tissue engineering a basic liver unit for therapeutic implantation.
Research Overview
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 & Funding
- The Role of Matrix Rigidity and Hepatocyte Mechanotransduction in Fibrotic Liver DiseaseSponsor: NIHSponsor ID: R01DK114311Funding Period:Jul 2017-Jun 2022Principal Investigator
- Defining the mechanism of function and engraftment potential of human hepatocyte organoidsSponsor: American College of SurgeonsSponsor ID: Clowes Research Career Development AwardFunding Period:Jul 2017-Jun 2022
- Liver tissue engineering in spaceSponsor: NSF/CASISSponsor ID: 18-514Funding Period:Sep 2018-Aug 2021Principal Investigator
- Using organoids to determine gravity effects on organogenesis and vasculogenesisSponsor: NASASponsor ID: 16-16ROSBDFP-0030Funding Period:Sep 2018-Aug 2020Principal Investigator
- Innovating a method of in situ decellularization followed by organoid engraftmentSponsor: Open Philanthropy ProjectSponsor ID: Transformational Research ProposalFunding Period:Jul 2017-Jun 2020PI
- Pioneering regenerative surgery - Mechanisms of cell death and regeneration in liver treated with non-thermal irreversible electroporation (NTIRE)Sponsor: NIHSponsor ID: R21EB024135Funding Period:Jan 2018-Dec 2019Principal Investigator
Publications
MOST RECENT PUBLICATIONS FROM A TOTAL OF 37
- Han S, Dicker ML, Lopez-Ichikawa M, Vu NK, Rubinsky B, Chang TT. Irreversible Electroporation of the Liver Increases the Transplant Engraftment of Hepatocytes. J Surg Res. 2023 Sep 20; 293:128-135. View in PubMed
- Nastase G, Botea F, Be?chea GA, Câmpean ?I, Barcu A, Neac?u I, Herlea V, Popescu I, Chang TT, Rubinsky B, ?erban A. Isochoric Supercooling Organ Preservation System. Bioengineering (Basel). 2023 Aug 07; 10(8). View in PubMed
- Botea F, Nastase G, Herlea V, Chang TT, ?erban A, Barcu A, Rubinsky B, Popescu I. An exploratory study on isochoric supercooling preservation of the pig liver. Biochem Biophys Rep. 2023 Jul; 34:101485. View in PubMed
- Zhang Y, Lv Y, Wang Y, Chang TT, Rubinsky B. Pancreatic islets implanted in an irreversible electroporation generated extracellular matrix in the liver. Radiol Oncol. 2023 03 01; 57(1):51-58. View in PubMed
- Weng Y, Han S, Sekyi MT, Su T, Mattis AN, Chang TT. Self-Assembled Matrigel-Free iPSC-Derived Liver Organoids Demonstrate Wide-Ranging Highly Differentiated Liver Functions. Stem Cells. 2023 03 02; 41(2):126-139. View in PubMed
- View All Publications
In the News
- The Chang Laboratory for Liver Tissue Engineering - - August 26, 2018Surgeon-scientist Tammy T. Chang, MD, PhD, principal investigator in the The Chang Laboratory for Liver Tissue Engineering, has been awarded grants by two prestigious federal funders of research, the NASA Space Biology Program, and the National Science Foundation (NSF) in collaboration with the Center for the Advancement of Science in Space (CASIS). Dr. Chang is a gastrointestinal surgeon who takes care of patients primarily in an acute care setting. She holds an appointment as an assistant [...]
- The Chang Laboratory for Liver Tissue Engineering - - May 26, 2017UCSF News Reports on a novel surgical approach to transplanting cells into diseased organs developed by Tammy T. Chang, MD, PhD, a gastrointestinal and acute care surgeon and principal investigator in the The Chang Laboratory for Liver Tissue Engineering, and Boris Rubinsky, PhD, Professor Emeritus of Bioengineering at UC Berkeley. The technique is called irreversible electroporation, or IRE, and enables newly transplanted clusters of liver cells, or hepatocytes to thrive and proliferate in a [...]
- UCSF Division of General Surgery - May 04, 2017The UCSF Division of General Surgery announces the launch of a new website for The Chang Laboratory for Liver Tissue Engineering. Tissue engineering and regeneration are the next evolutionary step in surgical practice. The lab's goal is to make significant contributions to bringing regenerative surgical therapies from the lab into the operating room. The lab focuses on a complex and vital solid organ, the liver to address the great clinical need to develop alternative therapies for end stage [...]
- UCSF General Surgery - November 01, 2016Tammy T. Chang, M.D., Ph.D. has received a five-year career development award from the American College of Surgeons (ACS). The George H. A. Clowes, Jr., MD, FACS, Memorial Research Career Development Award is offered through the The Clowes Fund, Inc., of Indianapolis, IN to provide support for the research of promising young surgical investigators. Dr. Chang is Assistant Professor of Surgery in the Division of General Surgery. She has a strong commitment to translating advances in laboratory [...]