|
|
Dr. Julian J. Lum, Ph.D.
 View Publications
| Department: |
Deeley Research Centre
(@ the BCCRC since 2008) |
| Research Role: |
Research Scientist |
| Education: |
B.Sc. (Biochemistry), University of Ottawa, 1999
Ph.D. (Microbiology and Immunology), University of Ottawa, 2002
|
| Phone: |
250-519-5718 |
| Fax: |
250-519-2040 |
|
Research Interests:
• Autophagy
• T cells
• Tumorigenesis
Background: Dr. Lum was born in the suburbs of Ottawa, Ontario graduating cum laude Bachelor of Science majoring in Biochemistry at the University of Ottawa in 1999. He stayed at the University of Ottawa and joined the laboratory of Andrew D. Badley, M.D. (Mayo Clinic, Rochester. Minnesota) to pursue his Ph.D in Microbiology and Immunology. During his graduate work, Dr. Lum studied the regulation of death receptor-mediated apoptosis of CD4 T cells. His work focused on TNF-Related Apoptosis Inducing Ligand (TRAIL) during HIV infection and its physiological role in neutrophil homeostasis. His graduate work culminated into seven first authored publications. In 2003, Dr. Lum pursued post-doctoral training with Craig B. Thompson at the University of Pennsylvania. For the last five years, he has been interested in how metabolic stress regulates autophagy and consequentially T cell function. Dr. Lum was recruited to the BC Cancer Agency in 2008 where he will continue his long-standing interest in pathways regulation cell death and survival.
Description of Research:
My laboratory is interested in studying how cellular metabolism regulates autophagy in the immune system and how this affects the process of tumorigenesis. We plan to study autophagy and its role in controlling lymphocyte effector functions in nutrient limited tumor sites. These studies are driven by the hypothesis that autophagy can promote lymphocyte cell survival. In addition, we are undertaking studies to examine how autophagy may impact on tumor antigen cross-presentation. These investigations will be used to direct novel immunotherapy approaches to treat cancer
Studies of T cell immune responses: bioenergetic control of T cell function. All T cells require the sufficient uptake and metabolism of extracellular nutrients to supply bioenergetics for maintenance of tissue homeostasis and cell survival. In the absence of critical nutrients including oxygen, glucose and amino acids, cells activate survival programs to provide a temporary means to sustain adequate ATP levels. A major hurdle in adoptive immunotherapy is the rapid induction of apoptosis of transplanted T cells. The molecular events governing this dramatic loss in T cells viability is unclear. We plan to investigate whether changes in nutrient conditionsex vivo may play a role in the death of transplanted T cells. This will consist of studies to determine how the nutrient environment of tumors impact adaptive T cell responses including CD8 T cell killer activity, secretion of anti-tumor cytokines, CD4 T cell helper activity, generation of memory T cells, and proper antigen presentation by dendritic cells. We will use a combination of xenograph mouse models, transgenic and knock-out mice to address these questions.
The bioenergetics of autophagy in cancer. A key question in cancer biology is the mechanism by which autophagy promotes bioenergetics and survival of tumors. Autophagy is a catabolic process cells use to degrade and recycle cellular constituents for the production of ATP. The substrates and end-products of autophagy are unknown. We hypothesize that autophagy must provide carbon sources for generation of reducing equivalents in the TCA cycle that can be used for ATP coupled oxidative phosphorylation. Given the extensive number of cancers that display increased autophagy, these studies may reveal a crucial therapeutic target to treat tumors. These studies will focus on the use of nuclear magnetic resonance (NMR) to trace the fate of metabolites in cells undergoing autophagy.
Targeting metabolic pathways by immunotherapy.
In the early 1920´s, Otto Warburg made a seminal observation that ascite tumor cells display a unique form of cellular metabolism. Warburg postulated that tumor rely on high rates of glycolysis to fuel tumor cell growth and proliferation. Although the precise mechanism for this addiction to glucose is not clear, recent work has suggested that oncogenes play a critical role in controlling glycolytic enzyme expression and glucose metabolism. Several metabolic enzymes have restricted and unique isoforms expression in tumors. This provides a window of opportunity to target these tumor specific isoforms using T cell-based therapies. Therefore, we are developing a platform to generate T cells with potent anti-tumor activity against these enzymes to test whether proteins involved in metabolism are antigenic.
Do cancer stem cells rely on autophagy for survival?
In general, stems cells are thought to be long-lived self-renewing cells that are capable of repopulating diverse cellular pools. By analogy, cancer stem cells may also possess this capacity to cause reseeding of cells into the bulk tumors. Despite our success in treating primary tumors, many patients experience tumor relapse and ultimately succumb to death. We are exploring the possibility that cancer stem cells utilize autophagy to survive for long periods. It is envisioned that this work will allow development of immunotherapy approaches that target and eliminate these cancer cell reservoirs.
URL: http://www.bccrc.ca/drc/people_jjlum.html
The BC Cancer Agency Research Centre is the research arm of the BC Cancer Agency (BCCA),
and is supported by the BC Cancer Foundation.
This page was last modified at 8:44am on August 20, 2009
© 1999-2008.
BC Cancer Agency. All rights reserved.
About this website...
|
|
|
|
Navigation Menu
View Site Map
Contact Us
BC Cancer Agency Research Centre
675 West 10th Avenue
Vancouver, BC
V5Z 1L3 Canada
1-604-675-8000
| |
|
jjlum@bccancer.bc.ca
Biochemistry and Microbiology
Prev
Comments/Questions about this page?