Philip S. LowRalph C. Corley Distinguished Professor—Biochemistry
Office: WTHR 331B
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Our laboratory focuses primarily on the development of ligand-targeted imaging and therapeutic agents for the diagnosis and treatment of important human diseases. First, we are designing, synthesizing and testing targeting ligands for their abilities to deliver attached drugs specifically to pathologic cells, avoiding unwanted uptake by healthy cells. Low molecular weight ligands currently under development or already in clinical trials include ligands designed to target cancers, inflammatory/autoimmune diseases, and a variety of infectious diseases. Because a receptor for the ligand, folic acid, is significantly over-expressed on many human cancers, we are attaching folate to already established drugs to facilitate their selective accumulation in malignant tissues. Folate-targeted drugs tested to date include: i) radioimaging agents, ii) chemotherapeutic drugs, iii) gene therapy constructs, iv) nanomedicines, v) protein toxins, vi) radiotherapeutic complexes, vii) MRI contrast agents, viii) therapeutic oligonucleotides, and ix) optical imaging agents for fluorescence-guided surgery of cancer. Five folate-targeted drugs from this work are currently undergoing human clinical trials for cancer, and one folate-targeted fluorescent dye is being tested in humans for fluorescence-guided surgery.
While imaging cancer patients, we discovered that activated macrophages (but not resting macrophages or other hematopoietic cells) also express a receptor for folic acid. Because this subpopulation of macrophages either causes or worsens most inflammatory/autoimmune diseases, including rheumatoid arthritis, atherosclerosis, ulcerative colitis, Crohn’s disease, psoriasis, multiple sclerosis, uveitis, systemic lupus erythematosis, and osteoarthritis, we have undertaken to develop folate-targeted therapies for the above pathologies. This research has led to development of a drug that successfully treats several of the above diseases in animals and will soon be tested in human clinical trials.
As noted above, a third major focus of our lab has been to develop novel targeting ligands for diseased cells that do not express folate receptors. One of these ligands, termed DUPA, has been shown to target both imaging and therapeutic agents to prostate specific membrane antigen expressing cells in both human prostate cancer patients and in animal models of the same malignancy. Other high affinity targeting ligands that can delivery drugs specifically to 1) other human cancers, 2) other pathologic immune cells, and 3) a variety of infectious pathogens are also under development. Together these ligands should enable higher resolution imaging and more effective/less toxic therapy for most prominent human diseases.
Finally, we are investigating the function and molecular organization of the human red blood cell membrane (see cartoon). Included in this research are projects aimed at characterizing: i) interactions between the membrane and its underlying cytoskeleton, ii) the signal transduction pathways that control cell function and morphology, and iii) the crystallographic structure of important membrane proteins. Because much of this information has proven relevant to identification of components involved in the transmission and propagation of malaria, we are exploiting this research to develop a novel mutation-resistant therapy for the disease.
EducationB.S., 1971, Brigham Young University; Ph.D., 1975, University of California, San Diego.
- Outstanding Commercialization Award for Purdue University Faculty, 2006
- National Institutes of Health MERIT Award, 1999
- Elected Fellow of the American Association for the Advancement of Science, 1998
- Sigma Xi Research Award, 1997
- Herbert Newby McCoy Award(Purdue University’s award for the best research on campus), 1993
- Indiana Lions Club Cancer Research Award, 1991
- International Union Against Cancer Fellow, 1987
- Research Associate, University of Massachusetts, 1975-76
- Chu, H.; Puchulu-Campanella, E.; Galan, J.A.; Tao, W.A.; Low, P.S.; Hoffman, J.F., Identification of cytoskeletal elements that enclose the ATP pools that fuel the human red blood cell membrane’s cation pumps. Proc. Natl. Acad. Sci 2012 , 109(31), 12794-9.
- van Dam, G.M.; Themelis, G.; Crane, L. M. A.; Harlaar, N. J.; Pleijhuis, R. G.; Kelder, W.; Sarantopoulos, A.; de Jong, J. S.; Arts, H. J. G.; van der Zee, A. G. J.; Bart, J.; Low, P. S.; Ntziachristos, V., Intraoperative Tumor-Specific Fluorescent Imaging in Ovarian Cancer by Folate Receptor-α Targeting: First In-Human Results. Nature Medicine 2011 , 17, 1315-19.
- Kularatne S. A.;Wang, K.;Santhapuram, H. K. R.;Low, P. S., Prostate-Specific Membrane Antigen Targeted Imaging and Therapy of Prostate Cancer Using a PSMA Inhibitor as a Homing Ligand . Molecular Pharmaceutics 2009 , 6 , 780-789.