Philip S. Low

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

We have developed methods to target drugs specifically to diseased cells, thereby avoiding collateral toxicity to healthy cells. To achieve this specificity, we have designed low molecular weight targeting ligands that bind selectively to pathologic cells and have linked them to the desired therapeutic or imaging agents. In the case of cancer, we have exploited the up-regulation of folate receptors on ~40% of human cancers to target the following pharmaceuticals to tumor masses: i) cytotoxic drugs, ii) protein toxins, iii) miRNA and siRNA constructs, iv) fluorescent dyes for fluorescence-guided surgery, v) radioimaging agents, vi) CAR T cells, vii) liposomes with entrapped drugs, viii) radiotherapeutic agents, ix) immunotherapeutic agents, and x) enzyme constructs for prodrug therapy. More recently, we have developed novel targeting ligands for most other cancers and tumor stromal cells, including regulatory T cells, MDSCs, tumor associated macrophages, and cancer associated fibroblasts (CAFs). In the course of these latter studies we have found that reprogramming of tumor stromal cells can have a profound impact on tumor growth and survival. Finally, we have also developed targeted therapies for many other diseases, including inflammatory diseases (rheumatoid arthritis, psoriasis, multiple sclerosis, ulcerative colitis, atherosclerosis, Crohn’s disease, sarcoidosis, systemic lupus erythematosus, etc.), viral infections (HIV, hepatitis B, influenza, etc.), fibrotic diseases (cirrhosis of the liver, idiopathic pulmonary fibrosis, scleroderma, etc.), inherited diseases (sickle cell disease, etc.), CNS diseases (Parkinson’s disease, Alzheimer’s disease, autism, etc.), and traumatized tissues. By concentrating the healing power solely in the cells that need it, we reduce/eliminate off-target toxicity while improving on-target efficacy.

Selected Publications:

1. The Role of Hemoglobin Denaturation and Band 3 Clustering in Red Blood Cell Aging. Low P.S., Waugh S.M., Zinke K. and Drenckhahn D., Science 227, 531-533 (1985) PMID: 2578228.

2. Delivery of Macromolecules into Living Cells: A Method that Exploits Folate Receptor Endocytosis. Leamon C.P. and Low P.S., Proc. Natl. Acad. Sci. USA 88, 5572-5576 (1991) PMID: 2062838.

3. Assembly and Regulation of a Glycolytic Enzyme Complex on the Human Erythrocyte Membrane. Campanella, M.E., Chu, H. and P.S. Low, Proc. Natl. Acad. Sci. 102, 2402-2407 (2005) PMID: 15701694.

4. A Functional Folate Receptor is Induced During Macrophage Activation and Can Be Used to Target Drugs to Activated Macrophages. Xia W, Hilgenbrink AR, Matteson EL, Lockwood MB, Cheng JX, Low PS. Blood 113, 438-46 (2009) PMID: 18952896.

5. Prostate-Specific Membrane Antigen (PSMA)-Targeted Imaging and Therapy of Prostate Cancer Using a PSMA Inhibitor as a Homing Ligand. Kularatne, S.A., Wang, K., Santhapuram, H.K.R., Low, P.S. Molecular Pharmaceutics 6, 780-789 (2009) PMID: 19361233.

6. Intraoperative Tumor-Specific Fluorescent Imaging in Ovarian Cancer by Folate Receptor-α Targeting: First In-Human Results. 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. Nature Medicine 17: 1315-19 (2011) PMID: 21926976.

7. Principles in the design of ligand-targeted cancer therapeutic and imaging agents. Srinivasarao M, Low PS. Nature Rev Drug Discov 14:203-19 (2015). PMID: 25698644.

8. Global Transformation of Eythrocyte Properties via Engagement of an SH2-like Sequence in Band 3. Puchulu-Campanella, E Turrini, FM, Yen-Hsing Li and Low, PS. Proc. Natl. Acad. Sci. USA 113: 13732-7 (2016) PMID: 27856737.

9. Evaluation of a Novel Tumor-Targeted Near-Infrared Probe for Fluorescence-Guided Surgery of Cancer. Mahalingam SM, Kularatne SA, Myers CH, Gagare P, Norshi M, Liu X, Singhal S, Low PS. J Med. Chem. 61:9637-9646 (2018) PMID: 30296376.

10. Regulation of CAR T cell-mediated cytokine release syndrome-like toxicity using low molecular weight adapters. Lee YG, Chu H, Lu Y, Leamon CP, Srinivasarao M, Putt KS, & Low PS. Nature Commun. 10:2681-9 (2019) PMID: 31213606.

11. Inhibition of Band 3 Tyrosine Phosphorylation: A New Mechanism for Treatment of Sickle Cell Disease. Noomuna, P, Risinger, M, Zhou, S, Seu, K, Man, Y, An, R, Sheik, DA, Wan, J, Little, JA, Gurkan, UA, Turrini, FM, Kalfa, T, and Low PS. Brit. J. Haematol. 190: xx (2020). P, Rubins D, Lin SA, Zeng Z, Haley H, Miller P, González Trotter D, Low PS. Mol Pharm 13(5):1520-7 (2016).