Academic background

  • PhD, University of British Columbia, Biomedical Research Centre ) then moved with advisor to Howard Hughes Medical Institute, University of California San Diego, (Genetics Program). 1990 – 1997
  • BSc, University of British Columbia, (Microbiology & Immunology). 1985 – 1989
Primary Research Area
Infectious Diseases and Immunopathology
Secondary Research Area
Blood research

Research Interest

  • Autoimmunity
  • Primary Immunodeficiency Diseases
  • Immune Regulation
  • T cell function

Summary

T cells form an integral part of our immune system and are essential to fight off most infections. To perform these roles, T cells must be able to differentiate between a variety of different antigens (defined as molecules that elicit immune responses). Excessive T cell responses towards harmless-(eg. dietary) antigens may result in dangerous food allergies while T cell attack against self-antigens (healthy cells or tissue) may cause T cell-mediated self-destruction (autoimmune disease). Conversely, dampened T cell responses against infected or malignant cells may lead to immunodeficiency (associated with chronic or life-threatening infections) or expansion of cancerous cells (tumour growth). By adding to the knowledge of how T cells can be turned “on” or “off”, we hope to uncover new therapies for human diseases related to allergy, autoimmunity, immunodeficiency and cancer.

Current Projects

X-linked lymphoproliferative disease
Epstein-Barr virus (EBV) is a γ-herpesvirus that infects more than 90% of the adult population, often resulting in subclinical or self-limiting infections. However, EBV poses serious health consequences for immunocompromised individuals, such as patients undergoing transplant or chemotherapeutic regimens, and is strongly associated with an expanding list of human cancers. To gain insight into immunity against EBV, we are studying a rare congenital immunodeficiency defined by exquisite sensitivity to EBV but not other pathogens called X-linked lymphoproliferative disease, a syndrome caused by mutations in the SH2D1A gene that encodes SLAM-associated protein (SAP). The inability of boys with XLP to control EBV infection results in fulminant, often fatal, infectious mononucleosis, massive expansions of EBV-infected B cells and malignant B cell lymphomas. To uncover how SAP loss contributes to susceptibility to EBV, we are investigating the role of SAP and SLAM receptors in the regulation of B cell-driven immune responses.

Immunoregulation of autoreactive T cells
A breakdown of immunological tolerance can result in autoreactive T cells causing organ-specific (eg. type 1 diabetes) or system-wide autoimmune diseases (systemic lupus erythematosus). Multiple mechanisms collaborate to maintain T cell tolerance and curtail potentially lethal consequences stemming from one’s own immune system attacking normal, healthy tissues and cells. Although many autoreactive T cells are programmed to die during their development in the thymus, some escape into the periphery and are thought to be restrained by a tolerance mechanism called anergy (non-antigen responsive state). The preservation of autoreactive T cells through anergy may result in dire autoimmune consequences if their function could be reawakened. Conversely, the reinvigoration of anergized T cells could be of benefit for promoting anti-cancer immune responses. My research program utilizes both in vitro cellular immunology assays and mouse model systems to study the regulation of autoreactive T cells and delineate the roles of specific genes or signalling pathways in governing their function.

 

Teaching Interest

I have devoted myself to a career in science because I believe advancing the human condition and understanding the bases of human disease is essential for improving treatments. My enthusiasm for science has developed from a deep admiration for novel means to unlock life’s mysteries using critical thinking and scientific reasoning. Teaching is very important to me as it provides me a chance to positively affect students and perhaps, make my greatest impact on society. In contrast to the classic-style of professor lecturing/student note taking, I think that science classes need to be interactive so that one can receive feedback on how well students comprehending classroom lectures. I aspire to generate subject interest by adopting a number of strategies to engage students in the subject material rather than having students cram material into rote short-term memory for mid- and end-of-semester exams. Science is exciting and scientific breakthroughs lead to novel possibilities for the future and new realities. To emphasize the importance of scientific findings, I believe that it is essential to provide the historical perspective, how paradigms change and how new opportunities often develop. In addition, I intend to change things up from class to class by using different instructional methods such as Powerpoint presentations, handwriting of notes, audiovisuals and forming small discussion groups for problem- solving tasks. In addition, the curriculum would be supplemented online with class notes, weekly quizzes and bulletin boards for receiving questions, feedback and the organization of study groups.

Training Laboratory Personnel
I will draw upon my extensive laboratory training, both as a graduate student and post-doctoral fellow, and concentrate my greatest energies on teaching three aims immediately after a student enters my group. The first aim revolves around issues of personal safety and identifying the potential dangers associated with the chemicals and equipment being used. Moreover, The second aim is to teach scientific planning, focusing on selecting appropriate experimental controls and data interpretation. These steps are taken to improve their efficiency by recouping the greatest amount of information from their early experiments. The third aim will involve participation in a weekly laboratory journal club, presenting articles from high-impact journals. I think this aim is especially important as I have found students to often accept a paper’s findings at face value without much critical evaluation of the procedures and interpretations.

The presentation format will include:

  • an introduction addressing the big picture of the field and subsequently, clearly defining the scientific questions being tackled,
  • careful selection of figure data necessary to convey the novel findings of the study and explanation of the methodologies used, and
  • thoughtful discussion of the conclusions including the meanings of the investigation for the field and new questions that the article may have raised.

I think that this type of scientific presentation is key for developing confidence, encouraging “outside of the box” type thinking and critically evaluating the authors’ conclusions. Aside from learning about recent scientific findings and teaching invaluable presentation skills, this exercise will also be important for early education into the preparation and writing of manuscripts. Furthermore, I will encourage a multidisciplinary scientific approach so that students acquire new skills, broaden their research background, form collaborations and ensure their long-term career success. As students mature, they will attend scientific conferences, present their work to larger audiences, receive greater independence and scientific freedom, and participate in grant writing. In conclusion, the development of good mentor-trainee relationships will be one of my highest priorities.