department of surgery :: research programs :: faculty and research :: chong group

Anita S. Chong, PhD

Professor
Section of Transplantation, Department of Surgery
University of Chicago
5841 S. Maryland Ave., (MC 5026) Chicago, IL 60637
Phone: 773-702-5521
Email:

 

Education
B.Sc.: University of Malaya, Kuala Lumpur, Malaysia B. Sc. (Zoology)
with 1st Class Honors
Ph.D.: Department of Microbiology, John Curtin School of Medical
Research, Australian National University, Canberra, Australia Cell
Biology
Post-Doctoral Fellow.: Tufts University, Boston, MA. Department of
Pathology, School of Medicine
Research Associate.: University of Arizona, Tucson, AZ, Departments of
Biochemistry and Medicine

 

Chong Group Links

• Complete Bibliography
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Heart Transplant in mice

Skin Transplant in Mice

Regenerating mouse Islet

Visualizing alloreactive B cells

 

Transplantation tolerance and islet beta-cell regeneration

Transplantation tolerance promises to reshape the post-transplant care of the transplant recipient and promote the survival of the transplanted organ. A major focus of my research is defining the barriers that prevent the induction or maintenance of graft tolerance. We are also interested in understanding the bases of islet beta-cell regeneration.

 

Memory, B cells, alloantibodies and allograft tolerance

Relatively little is known of how B cell responses are controlled following allograft transplantaton, beyond the general notion of controlling the T cells that provide B cell help. We have determined that multiple mechanisms control B cell responses in tolerant mice; these include peripheral deletion of the mature subset of B cells, indirect suppression of B cell responses through the inhibition of T helper cells, and possibly direct suppression of B cell function. We recently observed that transplantation tolerance is prevented by the presence of pre-sensitized B cells or alloantibodies. We are now focused on investigating how pre-sensitized B cells and alloantibodies prevent the induction of tolerance, specifically by defining their abilities to alter the activation requirements of naïve alloreactive T cells, and on understanding the behavior of memory and long-lived plasma B cells.

 

Impact of innate immunity and bacterial infections on transplantation tolerance

It has long been noted that transplanted organs such as the skin, lung and small bowel are more immunogenic and resistant to tolerance induction than hearts, pancreas and kidney, but there is currently no unifying hypothesis for why this is so. We noted that a common feature of the organs that are resistant to tolerance induction is their constant exposure to environmental antigens and commensal microorganisms. We hypothesized that a concurrent exposure of the immune system to microbial organisms and alloantigens is more likely to occur with organs such as the skin, lung and small bowel compared to ‘cleaner’ organs such as hearts, pancreas and kidney. We are collaborating with Dr. Marisa Alegre (Department of Medicine) and Dr. Chyung-Ru Wang (Department of Pathology) to test this hypothesis.

Microbial products contain pathogen-associated molecular patterns (PAMPs) that can activate Toll-like receptors (TLRs) on immune cells. We observed that synthetic TLR ligands can prevent the induction of allograft tolerance, while the inability to sense TLR-engagement promotes the tolerigenicity of skin allografts. We have also tested the effects of live bacterial infection on the stimulation of alloreactivity and the development of allograft tolerance. We observed that Listeria monocytogenes as well as Staphylococcus aureus infections prevented the development and reversed established tolerance. Studies are currently aimed at further defining the mechanisms by which TLR ligands and bacterial infections antagonize the development and maintenance of allograft tolerance. These studies could lead to new strategies that will facilitate the development and maintenance of allograft tolerance in transplant patients.

 

Islet Transplantation and restoration of islet beta-cell mass

Autoimmune-mediated destruction of beta cells is the predominant cause of Type I diabetes (TIDM). Beta cell replacement through pancreatic islet cell transplantation is a theoretically attractive treatment for type 1 diabetes. Indeed recent clinical successes support this notion, but also reveal significant limitations. These limitations include the recurrence of autoimmunity, risks associated with systemic immunosuppression to control alloreactivity, the limited availability of pancreatic islets for transplantation, and the relative transient reversal of diabetes. Using mice generated by Dr. Manami Hara (Section of Endocrinology), and in collaboration with Dr. Louis Philipson (Section of Endocrinology), we are investigating the mechanisms of beta-cell regeneration, with the goal of identify therapeutic targets for enhancing regeneration.

 

Selected Publications

The Department of Surgery • Section of Surgical Research • Surgery Brain Research Building, Room J557 • 5841 South Maryland Ave., MC 5032 • Chicago, IL 60637
Karl S. Matlin, PhD  •  Professor and Vice-Chair for Research  • (773) 834-8044 (phone)  • (773) 834-4546 (fax)
@ 2008 The University of Chicago Department of Surgery

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