Scientist profiles G-L
Sunnybrook Research Institute
Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room S1 11
Administrative Assistant: Melanie Suttar
Phone: 416.480.6100, ext. 3536
- B.Sc., 1974, Physiology/Pharmacology, University of Toronto, Canada
- PhD, 1979, Division of Experimental Pathology, Department of Pathology, University of Toronto, Canada
- Postdoctoral fellowship, 1979–1981, A.R.C. Institute, Babraham, U.K.
Appointments and Affiliations:
- Senior scientist, biological sciences, Brain Sciences Research Program, Sunnybrook Research Institute
- Professor, laboratory medicine and pathobiology, University of Toronto
Studies on the lymphatic circulatory system
Impact of radiation on lymphatic function; relevance to breast cancer-related lymphedema
An important consequence of lymph node excision during breast cancer surgery is the development of lymphedema in a significant number of patients. Lymphedema is a difficult, long-term problem for cancer survivors as quality of life is significantly compromised. Radiotherapy greatly increases the risk of developing lymphedema and yet we know very little about the mechanisms involved. In this study, we hope to characterize the most important radiation-induced lymphatic defects in the hope that these data will facilitate the development of protocols that mitigate lymphatic damage and reduce the incidence of lymphedema.
Hydrocephalus and lymphatic cerebrospinal fluid (CSF) absorption
Current surgical therapies for hydrocephalus leave much to be desired. In those cases in which an impediment to CSF absorption is contributing to ventricular enlargement, it would be very helpful if the removal of CSF could be facilitated with drugs. My group has examined CSF drainage mechanisms for many years and has concluded that a significant proportion of clearance occurs via lymphatic vessels external to the cranium. One intriguing property of these vessels is that many lymphatics in different parts of the body are capable of contracting and this activity provides much of the force required for lymph movement. Since these vessels are responsive to a wide variety of drugs, it is possible that pharmaceuticals can be used to modulate lymphatic function in hydrocephalus patients to promote CSF clearance. The purpose of this study is to examine the responsiveness of these lymphatic vessels to selected drugs applied via an intranasal route. If the results show promise, we may be able to reverse ventricular expansion in hydrocephalus without surgical intervention.
- Wilkie K, Nagra G, Johnston M. A mathematical analysis of physiological and molecular mechanisms that modulate pressure gradients and facilitate ventricular expansion in hydrocephalus. International Journal of Numerical Analysis and Modeling (series B). 2012; 3(1):65–81.
- Baker A, Kim H, Semple J, Shoichet M, Dumont D, Tobbia D, Johnston M. Experimental assessment of pro-lymphangiogenic growth factors as treatment for post-surgical lymphedema following lymphadenectomy. Breast Cancer Res. 2010 Sep; 12(5):R70.
- Nagra G, Li J, McAllister P, Wagshul M, Johnston M. Elevated CSF outflow resistance associated with impaired lymphatic CSF absorption in a rat model of kaolin-induced communicating hydrocephalus. Cerebrospinal Fluid Res. 2010 Feb; 7(1):4.
- Nagra G, Koh L, Kim M, Aubert I, Johnston M. Intraventricular injection of antibodies to beta1-integrins generates pressure gradients in the brain favoring hydrocephalus development in rats. Am J Physiol Regul Integr Comp Physiol. 2009 Nov; 297(5):R1312–1321.
- Tobbia D, Semple J, Baker A, Dumont D, Johnston M. Experimental assessment of autologous lymph node transplantation as treatment of post-surgical lymphedema. Plast Reconstr Surg. 2009 Sep; 124(3):777–786.
- Tobbia D, Semple J, Baker A, Semple A, Dumont D, Johnston M. Lymphatic Function and Lymphedema Development in Sheep Following Lymph Node Excision. J Vasc Res. 2009; 46(5):426–434.
- Nagra G, Li J, Mcallister P, Miller J, Wagshul ME, Johnston M. Impaired lymphatic cerebrospinal fluid absorption in a rat model of kaolin-induced communicating hydrocephalus. 2008 May; 294(5):R1752–1759.
- Nagra G, Johnston M. Impact of aging on lymphatic cerebrospinal fluid absorption in the rat. Neuropathol Appl Neurobiol. 2007 Dec; 33(6):684–691.
- Li J, Shen Y, McAllister II JP, Wagshul ME, Miller JM, Egnor M, Johnston MG, Haacke M, Walker ML. Communicating hydrocephalus in adult rats with obstruction of the basal cisterns or the cortical subarachnoid space. Exp Neurol. 2008 Jun; 211(2):351–361.
Related News and Stories:
- Award of Excellence: Sunnybrook researcher receives the 2006 Robert H. Pudenz Award of Excellence for Research in Cerebrospinal Fluid Physiology (December 17, 2007)
- Cool Summer Science: Student poster event fosters friendly competition and idea exchange (September 17, 2007)
- Challenging the Known: Miles Johnston discovers how cerebrospinal fluid really exits the brain, pointing toward future improvements in treatment for hydrocephalus (2004)