Tammy T. Chang, MD, PhD

Associate Professor
Surgery
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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.

Publications: 

Metastatic melanoma to small bowel: metastasectomy is supported in the era of immunotherapy and checkpoint inhibitors.

World journal of surgical oncology

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

Han S, Dicker ML, Lopez-Ichikawa M, Vu NK, Rubinsky B, Chang TT

Isochoric Supercooling Organ Preservation System.

Bioengineering (Basel, Switzerland)

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

Botea F, Nastase G, Herlea V, Chang TT, ?erban A, Barcu A, Rubinsky B, Popescu I

Self-assembled Matrigel-free iPSC-derived liver organoids demonstrate wide-ranging highly-differentiated liver functions

Stem Cells

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

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

Conroy PC, Colley A, Bongiovanni T, Chang TT, Harris H

Liver epithelial focal adhesion kinase modulates fibrogenesis and hedgehog signaling.

JCI insight

Weng Y, Lieberthal TJ, Zhou VX, Lopez-Ichikawa M, Armas-Phan M, Bond TK, Yoshida MC, Choi WT, Chang TT

Intra-Vital Imaging Demonstrates Robust Recruitment of Neutrophils after Irreversible Electroporation Tissue Ablation.

Journal of the American College of Surgeons

Maya A. Lopez-Ichikawa, Tammy T. Chang

Normal and fibrotic liver parenchyma respond differently to irreversible electroporation.

HPB : the official journal of the International Hepato Pancreato Biliary Association

Lyu C, Lopez-Ichikawa M, Rubinsky B, Chang TT

Liver Fibrosis: Current Approaches and Future Directions for Diagnosis and Treatment.

Fibrosis in Disease

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

Zhang Y, Lyu C, Liu Y, Lv Y, Chang TT, Rubinsky B

Reply.

Hepatology (Baltimore, Md.)

Chang TT

Direct orthotopic implantation of hepatic organoids.

The Journal of surgical research

Zhou VX, Lolas M, Chang TT

Force-dependent breaching of the basement membrane.

Matrix biology : journal of the International Society for Matrix Biology

Chang TT, Thakar D, Weaver VM

Hepatic Focal Adhesion Kinase Signaling Modulates Development of Liver Fibrosis.

Journal of the American College of Surgeons

Tammy T. Chang, Vivian X. Zhou

Gastrointestinal Zygomycosis Masquerading as Acute Appendicitis.

Case reports in gastroenterology

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.)

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

Hughes-Fulford M, Chang TT, Martinez EM, Li CF

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

Chang TT, Spurlock SM, Candelario TL, Grenon SM, Hughes-Fulford M

The Rel/NF-?B pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity.

Journal of leukocyte biology

Chang TT, Walther I, Li CF, Boonyaratanakornkit J, Galleri G, Meloni MA, Pippia P, Cogoli A, Hughes-Fulford M

Caudate split for open and laparoscopic liver resections.

Journal of the American College of Surgeons

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

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

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

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

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

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

Chang TT, Kuchroo VK, Sharpe AH