Hongbo Pang, PhD

Bio

The central question that Dr. Pang's lab focuses on is how to transport the cargo to the site of interest in human body with the high specificity and efficiency. His research synergizes multiple disciplines spanning from cell and cancer biology, peptide chemistry, nanomaterial to clinical imaging and cancer therapies. The ultimate goals are to discover new delivery technologies, decode the underlying transport machineries, and develop novel diagnosis and treatment for cancer and other human diseases.

Research Summary

Discovering new

The cornerstone of Dr. Pang's research is in vivo phage display, a powerful and high throughput technology to discover peptides selectively recognizing the cells/organs/tissues of interest. Upon systemic administration, these peptides are capable to travel, together with the imaging and therapeutic payloads, specifically to the target tissues/cells but not elsewhere. Ongoing projects aims at various immune cells in solid tumors (macrophages, regulatory T cells, dendritic cells, etc.), as well as cells within cardiovascular and nervous systems.

Understanding how

Upon identifying candidate peptides, Dr. Pang's lab elucidate the underlying mechanism to achieve tissue/cell-specific homing, and investigate the genetic networks of the host that regulate the efficiency of peptide-cargo transport. Solid tumors are a primary focus, the stroma of which represent a major challenge to drug delivery. Dr. Pang's research has unveiled a novel macropinocytic pathway into tumor cells, whose activity is regulated by nutrient availability and mTOR signaling. Additionally, his study revealed a cell-to-cell transport route that allows the cargo penetrating throughout tumor stroma. Ongoing research aims to decode the molecular machineries that regulate these transport pathways.

Achieving better

The ultimate goal of Dr. Pang's efforts is to improve the detection and therapies for human diseases through synergizing active targeting and delivery technologies. Currently his lab is pursuing two directions. The first is to combine tumor-targeting peptides with “etchable” nano-sized probes for MRI/PET imaging. These probes are of unique properties to lower the background “noise” in the circulation while increasing the signal intensity in tumors, thus enhancing the signal-to-noise ratio of tumor detection. The second project is to apply active targeting and nanomaterials in improving the delivery and thus clinical efficacy of nucleotide-based drugs into solid tumors.

Li YX, Pang HB. Macropinocytosis as a cell entry route for peptide-functionalized and bystander nanoparticles. Journal of Controlled Release, 2020, DOI: 10.1016/j.jconrel.2020.10.049

Pang HB*, Braun GB, Ruoslahti E*. Neuropilin-1 and heparan sulfate proteoglycans cooperate in cellular uptake of nanoparticles functionalized by cationic cell-penetrating peptides. Science Advances, 2015 Nov 6;1(10): e1500821. PMCID: PMC4640594.

*Co-corresponding author.

Pang HB, Braun GB, Friman T, Aza-Blanc P, Ruidiaz M, Sugahara KN, Teesula T, Ruoslahti E. An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability. Nature Communications, 2014 Oct 3;5: 4904.

Pang HB, Braun GB, She ZG, Kotamraju VR, Sugahara KN, Teesalu T, Ruoslahti E. A free cysteine prolongs the half-life of a homing peptide and improves its tumor-penetrating activity. Journal of Controlled Release, 2014, 175: 48-53.

Kim B*, Pang HB*, Kang J, Park JH, Ruoslahti E and Sailor MJ. Macrophage-targeting fusogenic nanoparticles for potent immunogene therapy against bacterial infection. Submitted.

*Equal Contribution.

She ZG, Hamzah J, Kotamraju VR, Pang HB, Jansen S, Ruoslahti E. Plaquepenetrating peptide inhibits development of hypoxic atherosclerotic plaque. The Journal of Controlled Release, 2016 Sep 28;238:212-20.

She ZG, Chang Y, Pang HB, Chen H, Liu DP, Witztum JL, Smith JW, Stallcup WB. NG2 Ablation Reduces Low-Density Lipoprotein Retention of Synthetic Smooth Muscle Cells and Atherogenesis. Arterioscler Thromb Vasc Biol, 2015 Nov 5. pii: ATVBAHA.115.306074. PMID: 26543095.

Braun GB, Friman T, Pang HB, Pallaoro A, de Mendoza TH, Willmore AM, Kotamraju VR, Mann AP, She ZG, Sugahara KN, Reich NO, Teesalu T, Ruoslahti E. Etchable plasmonic nanoparticle probes to image and quantify cellular internalization. Nature Materials, 2014, 13(9): 904-11. DOI:10.1038/nmat3982. PMCID: PMC4141013.

Pang HB, Hevroni L, Kol N, Eckert DM, Tsvitov M, Kay MS, Rousso I. Virion Stiffness Regulates Immature HIV-1 Entry. Retrovirology, 2013, 10(1):4. DOI: 10.1186/1742-4690-10-4. PMCID: PMC3564805.

Kol N, Tsvitov M, Hevroni L, Wolf SG, Pang HB, Kay MS, Rousso I. The effect of purification method on the completeness of the immature HIV-1 Gag shell. The Journal of Virological Methods, 2010, 169(1):244-7. DOI: 10.1016/j.jviromet.2010.07.035. PMID: 20691213.

Kim S, Pang HB, Kay MS. Peptide mimic of the HIV envelope gp120-gp41 interface. The Journal of Molecular Biology, 2008, 376(3):786-97. DOI: 10.1016/j.jmb.2007.12.001. PMCID: PMC2265733.