Pediatric Surgery Lab »  Research »  MacKenzie Lab
Pediatric Surgery Lab »  Research »  MacKenzie Lab

MacKenzie Lab

The MacKenzie lab is one of the main basic and translational research arms of the division. As a member of the Broad Center for Regeneration Medicine and Stem Cell Research as well as the Biomedical Sciences Program, Dr. MacKenzie is able to integrate the expertise of the basic science community with the clinical needs of our pediatric and fetal surgical patients. The main goals of the lab are to treat congenital disorders with prenatal stem cell transplantation and to explore mechanisms of preterm labor after fetal intervention.

Fetal surgery started at UCSF over two decades ago as a way of treating rare, fatal congenital anomalies. With our growing understanding of the molecular basis of disease, we now have an opportunity to design less invasive methods such as stem cell transplantation or gene therapy to treat a variety of prenatally diagnosed disorders. For example, in utero stem cell transplantation can be used to treat diseases in which stem cells are missing or mutated, such as immunodeficiencies, inborn errors of metabolism, or muscular dystrophy. Prenatal gene transfer can be used to introduce missing proteins in single-gene disorders such as hemophilia or cystic fibrosis. The main advantage of this strategy is that early in gestation, the fetus is immunologically immature, which gives an opportunity to transplant allogeneic or xenogeneic cells without an immune response. In addition, the proliferative state of the fetus would nurture the migration and differentiation of transplanted (or genetically modified) stem cells. 

Prospective Fellows!

We are currently recruiting a post-doctoral fellow with experience in immunology. Interested applicants should contact Dr. MacKenzie at tippi.mackenzie@ucsfmedctr.org

Our lab studies in utero transplantation in the fetal mouse model with the goal of elucidating mechanisms of engraftment and tolerance induction. Recent experience in the mouse model has shown that there are barriers to engraftment in a fetus that remain poorly understood. We are currently examining both the fetal and the maternal immune responses to stem cell transplantation in order to improve engraftment.

Our lab is also studying the trafficking of cells between the mother and the fetus in order to understand the mechanisms of preterm labor. While there has been considerable work in defining fetal cells in the mother, trafficking of maternal cells into the fetus remains poorly understood. We have formed a multidisciplinary team to collect and analyze maternal and cord blood samples from fetuses with various congenital anomalies and preterm labor in order to determine whether changes in trafficking lead to fetal distress and preterm labor. We have also developed a mouse model in order to study the mechanisms which govern lymphocyte trafficking through the placenta.

tippi lab photo

Current lab members

  • Marta Wegorzewska, BMS graduate student, National Science Foundation grant
  • Michela Frascoli, post-doc
  • Ninnia Lescano, staff research assoc.
  • Chris Derdarian, post-doc
  • Shivika Trivedi, medical student

Former lab members

  • Catherine Tsai, medical student
  • Greg Emmanuel: medical student
  • Erin Jarvis, Staff Research Associate
  • Eisha Zaid, medical student
  • Amar Nijagal, post-doctoral fellow, CIRM Postdoctoral Research Grant
  • Tom Le, Staff Research Associate
  • Geoanna Bautista, graduate student
  • Andrew Tucker

Collaborators

Funding Sources

  • American College of Surgeons Faculty Development Award
  • American Pediatric Surgery Association
  • American Surgical Association Foundation
  • March of Dimes Basil O'Conner Award
  • Irene Perstein Award
  • UCSF Broad Center for Regeneration Medicine and Stem Cell Research
  • UCSF Resource Allocation Program
  • UCSF Sandler Funds
  • Stem Cell Transplantation Immunology Award, California Institute of Regeneration Medicine
  • NIH/NIAID

Selected Publications

Nijagal A, Wegorzewska M, Jarvis E, Le T, Tang Q, MacKenzie TC. Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice. J Clin Invest. 2011 Feb 1; 121(2):582-92.

Nijagal A, Le T, Wegorzewska M, Mackenzie TC. A mouse model of in utero transplantation. J Vis Exp. 2011; (47).

Nijagal A, Fleck S, Hills NK, Feng S, Tang Q, Kang SM, Rosenthal P, Mackenzie TC. Decreased risk of graft failure with maternal liver transplantation in patients with biliary atresia. Am J Transplant. 2012 Feb; 12(2):409-19.

Nijagal A, Flake AW, Mackenzie TC. In utero hematopoietic cell transplantation for the treatment of congenital anomalies. Clin Perinatol. 2012 Jun; 39(2):301-10.

Saadai P, Lee TH, Bautista G, Gonzales KD, Nijagal A, Busch MP, Kim CJ, Romero R, Lee H, Hirose S, Rand L, Miniati D, Farmer DL, Mackenzie TC. Alterations in maternal-fetal cellular trafficking after fetal surgery. J Pediatr Surg. 2012 Jun; 47(6):1089-94.

See all PubMed entries for Tippi MacKenzie.

 

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