Professor Emeritus
Anatomy & Neurobiology
113 Irvine Hall
rtrobert@uci.edu
Working to Understand: cell surface molecules that identify certain classes of cells.
Scientific Foci, Cancer: use of peptide-containing liposomes and immuno-liposomes to identify cell surface molecules of tumor cells for delivery of chemotherapeutic drugs specifically to targeted cancer cells.
Scientific Foci, Neuroscience: studies of expression of cell-secreted neurotrophins that aid axonal target selection in developing cerebral cortex, including both neocortex and hippocampal formation. Experiments use tissue slice and dissociated cell culture techniques to understand how expression of neurotrophin-3 guides cholinergic axons to form synapses with cortical neurons.
Research Description and Approach
Dr. Robertson focuses his research efforts on studying the cellular basis of molecules that identify certain classes of cells.
Application to Cancer Research
A major goal in cancer research is the development of systems to deliver chemotherapeutic agents directly to tumor cells and away from normal tissue. Such systems would allow lower doses of the chemotherapeutic agents, and would reduce the negative side effects resulting from impact on normal tissues.
Our work takes a novel approach towards this goal, which is to package the chemotherapeutic drug in tiny lipid spheres, called liposomes. To deliver these liposome packages selectively to cancer cells, we engineer the liposomes to have either a surface peptide or a surface antibody fragment, designed to target the glycosaminoglycan extracellular matrix molecules that characterize tumor tissue.
Glycosaminoglycans, as part of the extracellular matrix, are a common feature on the surfaces of cells, including tumor cells. Importantly, tumors exhibit a dysregulation of both the composition and level of glycosaminoglycans, compared to normal tissues; these abnormal glycosaminoglycans offer selective targets for anti-cancer delivery mechanisms.
Application to Alzheimer’s Research
Alzheimer’s is well studied, and a variety of investigations in recent years have provided detailed information about what goes wrong in Alzheimer’s disease; we just don’t know why.
Because we know that one of the major pathological features of Alzheimer’s disease is the loss of cholinergic circuits (systems that use acetylcholine as a neural transmitter), and loss of these cholinergic circuits seems somehow tied to the development of amyloid plaques in the Alzheimer brain, the Robertson laboratory is studying the normal development of these cholinergic circuits.
Perhaps by understanding the development of these brain systems, and the neurotrophic factors needed by these systems during development, we can recreate the conditions that lead to neural growth early in life and rescue these circuits when they show signs of degenerating later in life.
Select Publications
Neuroscience
Robertson, R.T., J. Baratta, J. Yu and K.M. Guthrie. A role for neurotrophin 3 in target selection by developing cholinergic axonal projections to cerebral cortex. Neuroscience, 2006, 143, 523-539.
Lee, Y.-S., C.Y. Li, V. Caiozzo, R.T. Robertson, J. Yu and V, Lin. Repair of spinal cord transection and its effects on muscle mass and single fiber myosin heavy chain isoform phenotype. Journal of Applied Physiology, 2007, 103, 1808-1814.
Lee, Y.-S., A. Danandeh, J. Baratta, J. C.-Y. Lin, J.Yu, and R.T. Robertson. Neurotrophic factors rescue basal forebrain cholinergic neurons and improve performance on a spatial learning test. Experimental Neurology, 2013, 249, 178-186.
Robertson, R.T., J. Baratta, J. Yu and F.M. LaFerla. Amyloid-b expression in retrosplenial cortex of triple trangenic mice: relationship to cholinergic axonal afferents from medial septum. Neuroscience, 2009, 164, 1334-1346.
Sahyouni, R., P. Gutierrez, E. Gold, R.T. Robertson, and B. Cummings. The effects of concussion on the blood brain barrier in humans and rodents. Journal of Concussion, 2017, 1: 1-15.
Cancer Targeting
Robertson, R.T., J. Baratta, S.M. Haynes and K.J. Longmuir. Liposomes incorporating a Plasmodium amino acid sequence target heparan sulfate biding sites in liver. Journal of Pharmaceutical Sciences, 2008, 97, 3257-3273.
Baratta, J.L., A. Ngo, B. Lopez, N. Kasabwala, K.J. Longmuir and R.T. Robertson. Cellular organization of normal mouse liver: a histological, quantitative immunocytochemical, and fine structural analysis. Histochemistry and Cell Biology, 2009, 131, 713-726.
Longmuir, K.J., S.M. Haynes, J. Baratta, N. Kasabwala, and R.T. Robertson, Liposomal delivery of doxorubicin to liver and hepatocytes in vivo by targeting hepatic heparan sulfate glycosaminoglycan, International Journal of Pharmaceutics, 2009, 382, 222-233.
Robertson, R.T., Levine, S.T., Haynes, S.M., Gutierrez, P., Baratta, J.L., Tan, Z. and Longmuir, K. J. Use of labeled tomato lectin for imaging vascular structures. Histochemistry and Cell Biology, 2015, 143: 225-234.
Robertson, R.T., Gutierrez P. M., Baratta, J.L., Thordarson, K., Braslow, J., Haynes, S.M. and Longmuir, K.J. Development, differentiation, and vascular components of subcutaneous and intrahepatic Hepa129 tumors in a mouse model of hepatocellular carcinoma. Histology and Histopathology, 2016, 31: 403-413.