Senior Investigator, Lady Davis Institute
Chief of the Division of Nephrology, Jewish General Hospital
Associate Professor, Faculty of Medicine, McGill University
Dr. Mark L. Lipman is Chief of the Division of Nephrology and Associate Physician-in-Chief of the Department of Medicine at the Jewish General Hospital. He is an Associate Professor in the Faculty of Medicine of McGill University and Project Director at the Lady Davis Institute for Medical Research.
Dr. Lipman’s primary research focus is in the field of transplantation immunobiology. His lab has identified molecular markers of immunological rejection and has demonstrated expression of pro-inflammatory cytokines, by quantitative PCR techniques, even in the absence of overt graft dysfunction in protocol renal biopsies. This newly recognized phenomenon, termed subclinical rejection, likely contributes to the insidious development of chronic allograft nephropathy, which, in turn, is the leading cause of renal allograft failure. Ongoing studies will determine whether treatment decisions guided by molecular analysis of subclinical rejection will improve clinical outcomes.
His lab is also studying the degree of clonality of the graft-infiltrating T cell populations. Should rejection episodes be driven by a limited number of T cell clones, it would potentially facilitate the delivery of highly specific anti-rejection therapies, wherein only the clones attacking the transplanted organ are targeted, as opposed to conventional therapies, which weaken the recipient’s entire T cell population. Individualized immunotherapy would better protect the recipient’s immune system and reduce the predisposition to infections and certain cancers that afflict transplant patients. Here, anchor-PCR, cloning and sequencing is used to identify the highly variable DNA patterns of the T cell receptor which are molecular fingerprints of clonal populations.
A third project seeks to develop novel immunosuppressive agents. Dr. Lipman designed and constructed a hybrid fusion protein by combining Fas to the Fc region of IgG. Moreover, his lab has demonstrated that this molecule kills FasL-expressing activated T cells and can block cellular immune responses in mice.
In the area of clinical research, Dr. Lipman directs an extensive array of studies focused on the perturbations of the vascular-bone axis and the adverse consequences that accrue in patients with chronic kidney disease.
Major Research Activities
Dr. Lipman’s lab continues to use cutting-edge techniques to assay the degree of immunological activity in kidney transplants and to discern the populations of T-cells that drive specific rejection episodes. His lab is also testing the immunosuppressive potential of a ‘home made’ fusion protein.
Dr. Lipman directs several clinical research projects in the area of metabolic bone disease and vascular calcification in patients with chronic kidney disease.
Birnbaum LM, Lipman M, Paraskevas S, Chaudhury P, Tchervenkov J, Baran D, Herera-Gayol A, Cantarovich M. Management of chronic allograft nephropathy: A systematic review. Clinical Journal of the American Society of Nephrology 2009; Volume 4: 860.
Raju DL, Canatorvich M, Brisson M-L, Tchervenkov J, Lipman ML. Primary hyperoxaluria: Clinical course, diagnosis, and treatment after kidney failure. American Journal of Kidney Disease 2008; Volume 51: e1.
Lipman ML, Zhang Y, Loertscher R. Programmed Death Ligand-1 (PD-L1) gene expression correlates with acute subclinical rejection. American Journal of Transplantation 2008 ; Volume 8, Issue s2: 413.