Philip S. Low

Philip S.  Low Profile Picture

Ralph C. Corley Distinguished Professor
Ph.D. UC, San Diego, 1975

Contact Info:

Training Group(s):
Biomolecular Structure and Biophysics
Microbiology, Immunology and Infectious Diseases
Membrane Biology

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

Current Research Interests:

A major component of my research focuses on development of targeting ligands for the selective delivery of therapeutic and imaging agents to diseased cells; i.e. thereby avoiding the collateral toxicity that arises when nontargeted drugs enter healthy cells. In the case of cancer, we achieve this specificity by identifying cell surface proteins/receptors that are significantly upregulated on malignant cells, but expressed in limited numbers or not at all on normal cells. Following i.v. injection of ligand-linked imaging/therapeutic agents, the ligand-drug conjugates accumulate rapidly in cancer cells and clear within 1-3 hours from receptor-negative normal tissues. To date, we have developed targeting ligands for nearly all human cancers, as well as for multiple infectious, inflammatory and autoimmune diseases. Included in the receptors for which high affinity organic ligands have been designed and synthesized are the folate receptor, prostate specific membrane antigen, HSP90, galectin 3, neurokinin 1 receptor, fibroblast activation protein (FAP), cholecystokinin receptor 2, uPAR, LHRH receptor, EGF receptor, mu-opioid receptor, carbonic anhydrase IX, and the somatostatin receptor, etc. Importantly, 5 of our ligand-targeted drugs have entered human clinical trials for kidney, ovarian, breast, lung, brain, prostate, and endometrial cancers, and three successful companies (Endocyte Inc., On Target Laboratories Inc., and Umoja Biopharma) have been founded to commercialize these drug products. While many of our targeting ligands are exploited to deliver attached imaging and therapeutic agents to cancer cells, still others are used to deliver related pharmaceuticals to nonmalignant disease-causing cells, including cells involved in such pathologies as rheumatoid arthritis, Crohn’s disease, idiopathic pulmonary fibrosis, osteoarthritis, malaria and sickle cell disease. Importantly, 3 drugs from this class of targeted therapeutics are also currently undergoing human clinical trials and two companies have been founded to develop and commercialize them (HuLow LLC and Erythrocure Inc.). In a totally different area, we have also developed multiple bone fracture targeting ligands that we have exploited to deliver attached bone anabolic agents selectively to fracture surfaces. Following systemic (intravenous) injection, these fracture-homing conjugates are observed to concentrate on the fracture surface and promote significantly accelerated bone fracture repair without causing measurable off-target toxicity. With the anticipated growth in aging populations, morbidities and mortalities associated with hip fractures, nonunion fractures and spinal fusion operations are expected to increase. We anticipate that our systemically targeted bone anabolic agents will meet major unmet needs in these patient populations. Novosteo Inc. was formed to develop these technologies.

Selected Publications:

Use of a Single CAR T Cell and Several Bispecific Adapters Facilitates Eradication of Multiple Antigenically Different Solid Tumors. Lee YG, Marks I, Srinivasarao M, Kanduluru AK, Mahalingam SM, Liu X, Chu H, Low PS. Cancer Res. 79(2):387-396 (2019)

Evaluation of 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)

Ligand-Targeted Drug Delivery. Srinivasarao M, Low PS. Chem Rev. 117:12133-12164 (2017)

Healing efficacy of fracture-targeted GSK3β inhibitor-loaded micelles for improved fracture repair. Low SA, Galliford CV, Jones-Hall YL, Roy J, Yang J, Low PS, Kopeček J. Nanomedicine (Lond). 12(3):185-193 (2017).

Reversible binding of deoxyhemoglobin to band 3 constitutes the molecular switch that mediates O2 regulation of erythrocyte properties. Chu H, McKenna MM, Krump NA, Zheng S, Mendelsohn L, Thein SL, Garrett LJ, Bodine DM, Low PS. Blood. 128(23):2708-2716 (2016).

Global transformation of membrane properties via engagement of an SH2-like sequence in band 3. Puchulu-Campanella E, Turrini F, Li YH, Low PS. Proc Natl Acad Sci. 113(48):13732-13737 (2016).

Synthesis and Preclinical Evaluation of Folate-NOTA-AI18F for PET Imaging of Folate Receptor-Positive Tumors. Chen Q, Meng X, McQuade P, Rubins D, Lin SA, Zeng Z, Haley H, Miller P, González Trotter D, Low PS. Mol Pharm 13(5):1520-7 (2016).

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