Principal Investigator/Program Director (Last, First, Middle):
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Leaf Huang
Fred Eshelman Distinguished Professor and Chair
eRA COMMONS USER NAME
LEAFHUANG
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
National Taiwan University, Taipei
Michigan State
State University,
University, E.
E. Lansing,
Lansing, MI
MI
Michigan
Carnegie Institution of WA, Baltimore, MD
Carnegie Institution of WA, Baltimore, MD
DEGREE
(if applicable)
B.S.
Ph.D.
Postdoc
YEAR(s)
1968
1974
1974-76
FIELD OF STUDY
Physics
Biophysics
Biochemistry./Biophysics
PERSONAL STATEMENT:
I have been studying drug/gene delivery in my entire scientific career. We were the first (1990) to publish the
prolonged circulation time of the PEGylated liposomes. We have been a pioneer group in non-viral gene
delivery since the mid 80s. The cationic liposomes used in the first human clinical trial for non-viral gene
therapy in 1992 were designed and manufactured by us. In recent years, our focus has been the delivery of
oligonucleotides including siRNA using self-assembled nanoparticles invented by us. We were the first to show
that nanoparticles properly protected with a PEG brush could evade the reticuloendothelial system and
accumulate at a high level in the tumor after i.v. injection. We have recently shown that the core of the
nanoparticle could be replaced with a pH-sensitive calcium phosphate precipitate such that the nanoparticles
dissolve rapidly in the endosomal acidic pH to release the cargo into the cytoplasm. These milestone
accomplishments have placed us in an excellent position to further explore the potential of nanotechnology in
drug/gene delivery.
PROFESSIONAL EXPERIENCE:
1976- 1991 Assistant Professor, Associate Professor and Professor, Department of Biochemistry, University
of Tennessee, Knoxville, TN
1991- 1999 Professor, Department of Pharmacology, University of Pittsburgh, School of Medicine,
Pittsburgh, PA
1999- 2005 The Joseph Koslow Professor of Pharmaceutical Sciences, and Director, Center for
Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA
2005Fred Eshelman Distinguished Professor and Chair, Division of Molecular Pharmaceutics,
Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.
HONORS AND AWARDS:
1981-1986
Research Career Development Award, NIH
1982-1986
Member, Cellular Physiology and Biology II Study Section, NIH
1984-1991
Member, Center for Excellence, University of Tennessee, Knoxville, TN
1991-1994
Member, AIDS and Related Research Study Section 4, NIH
1991-1997
Editor-in-Chief, Journal of Liposome Research
1997
Elected Fellow, American Association of Pharmaceutical Scientists
1998-1999
Chairman, Non-viral Gene Therapy Committee, American Society for Gene Therapy
1999-2004
Associate Editor, Molecular Therapy (the official journal of ASGT)
1999-2002
Member, Medical Biochemistry Study Section, NIH
1999-2005
Joseph Koslow endowed chair professor of pharmaceutical sciences, Univ. of Pittsburgh
2003
Elected Fellow, American Institute for Medical and Biological Engineering
Principal Investigator/Program Director (Last, First, Middle):
2004
2006
2010
2011
Alec D Bangham MD FRS Achievement Award, Liposome Research Days Conference
Elected to Advisory Board, American Society of Gene and Cell Therapy
T. Nagai Postdoctoral Research Award, Controlled Release Society. Both postdoc (Dr. Sang
Kyoon Kim) and mentor (Leaf Huang) were honored.
Elected Vice Chair, Gordon Research Conference on “Cancer Nanotechnology”
RECENT PUBLICATIONS (Total refereed publications: 319, Reviews/Chapters: 130, H-index: 76)
Liu, F., Shollenberger, L., and Huang, L. Non-immunostimulatory nonviral vectors. FASEB Journal. 18: 177981, 2004.
Banerjee, R., Tyagi, P., Li, S., and Huang, L. Anisamide-targeted stealth liposomes: a potent carrier for
targeting doxorubicin to human prostate cancer cells. International J. of Cancer. 112: 693-700, 2004.
Cui, Z., Han, S-J, Huang, L. Coating of mannan on LPD nanoparticles containing HPV E7 peptide significantly
enhanced immunity against HPV-positive tumor. Pharmaceutical Research, 21:1018-1025, 2004.
Cui, Z., Han, S-J, Vangasseri, D-P, and Huang, L. The immunostimulation mechanism of LPD nanoparticles.
Molecular Pharmaceutics. 2: 22-28, 2005.
Cui, Z. & Huang, L. Liposome-polycation-DNA (LPD) particle as a carrier and adjuvant for protein-based
vaccines: Therapeutic effect against cervical cancer. Cancer Immunol. Immunother. 54:1180-1190,
2005.
Zhang, J., Liu, F., Conwell, C., Tan, Y., Huang, L. Mechanistic studies of sequential injection of cationic
liposome and plasmid DNA. Molecular Therapy, 13:429-437, 2006.
Vangasseri, D. Cui, Z., Chen, W., Hokey, D.A., Falo, L.D. and Huang, L. Immunostimulation of dendritic cells
by cationic liposomes. Mol. Memb. Biol. 23(5):1-11, 2006.
Li, S-D. and Huang, L. Gene therapy progress and prospects: non-viral gene therapy by systemic delivery.
Gene Therapy 13: 1313-1319, 2006.
Li, S-D, Huang, L. Targeted delivery of antisense oligodeoxynucleotide and small interference RNA into lung
cancer cells. Molecular Pharmaceutics. 3(5): 579-588, 2006.
Olton, D., Li, J., Wilson, M.E., Rogers, T., Close, J., Huang, L., Kumta, P.N., and Sfeir, C. Nanostructured
calcium phosphates (NanoCaPs) for non-viral gene delivery: influence of the synthesis parameters on
transfection efficiency. Biomaterials. 28: 1267 - 1279, 2007.
Lee, P.Y., Cobain, E., Huard, J., and Huang, L. Thermosensitive hydrogel PEG-PLGA-PEG enhances the
engraftment of muscle-derived stem cells and promotes healing in diabetic wound. Molecular
Therapy. 15(6): 1189 - 1194, 2007.
Yan, W., Chen, W.C. and Huang, L. Mechanism of adjuvant activity of cationic liposome: phosphorylation of a
MAP kinase, ERK and induction of chemokines. Molecular Immunology. 44: 3672 -3681, 2007.
Liu, F., Conwell, C.C., Yuan, X., Shollenberger, L.M., and Huang, L. Novel non-viral vectors target cellular
signaling pathways: regulated gene expression and reduced toxicity. J. Gene Med. 321:777-783, 2007.
Chen, W., Yan W., and Huang, L. A Simple but Effective Cancer Vaccine Consisting of an Antigen and a
Cationic Lipid. Cancer Immunology Immunotherapy. 57:517-530, 2008.
Li, S-D., Chen, Y-C., Hackett, M.J. and Huang, L. Tumor targeted delivery of siRNA by self-assembled
nanoparticles. Molecular Therapy. 16:163-169, 2008.
Conwell, C.C., Liu, F. and Huang, L. Several serum proteins significantly decrease inflammatory response to
lipid based nonviral vectors. Molecular Therapy, 16:370 - 377, 2008.
Li, S-D., and Huang, L. Efficient gene silencing in metastatic tumor by siRNA formulated in surface-modified
nanoparticles. J. Contr. Rel. 126:77 - 84, 2008.
Chen, W. and Huang, L. Induction of cytotoxic T-lymphocytes and anti-tumor activity by a liposomal
lipopeptide vaccine. Molecular Pharmaceutics. 5(3): 464 - 471, 2008.
Li, S-D., Chono, S., and Huang, L. Efficient oncogene silencing and metastasis inhibition via systemic delivery
of siRNA. Molecular Therapy. 16(5):942 - 946, 2008.
Yan, W., Chen, W., and Huang, L. Reactive oxygen species play a central role in the activity of cationic
liposome based cancer vaccine. J. Contr. Rel. 130: 22–28, 2008.
Chono, S., Li, S-D. Conwell, C.C. and Huang, L. An efficient and low immunostimulatory nanoparticle
formulation for systemic siRNA delivery to the tumor. J. Contr. Rel. 131: 64-69. 2008.
Chen, Y., Sen J., Bathula, S., Yang, Q., Fittipaldi, R., and Huang, L. Novel Cationic Lipid That Delivers siRNA
and Enhances Therapeutic Effect in Lung Cancer Cells. Molecular Pharmaceutics. 6:696-705, 2009.
PHS 398/2590 (Rev. 09/04)
Continuation Format Page
Principal Investigator/Program Director (Last, First, Middle):
Li, S-D, Huang, L. Nanoparticles Evading the Reticuloendothelial System: Role of the Supported Bilayer. BBA
– Biomembranes. 1788: 2259-2266, 2009.
Li, J. Chen, Y. Tseng, Y.-C., Mozumdar, S. And Huang, L. Biodegradable calcium phosphate nanoparticle with
lipid coating for systemic siRNA delivery. J. Contr. Rel. 142:416-421, 2010.
Chen, Y., Wu, J.J., and Huang, L. Nanoparticles Targeted with NGR Motif Deliver c-Myc siRNA and
Doxorubicin for Anticancer Therapy. Molecular Therapy. 18(4): 828 - 834, 2010.
Liu, Y., Huang, L., and Liu, F. Paclitaxel Nanocrystals for Overcoming Multidrug Resistance in Cancer.
Molecular Pharmaceutics. 7:863-869, 2010
Chen, Y., Bathula R., Li, J., and Huang, L. Multifunctional Nanoparticles Delivering siRNA and Doxorubicin
Overcome Drug Resistance in Cancer. Journal of Biological Chemistry. 285(29):22639-50, 2010.
Nakagawa, O., Ming, X., Huang, L., and Juliano, R.L. Targeted Intracellular Delivery of Antisense
Oligonucleotides Via Conjugation With Small Molecule Ligands. Journal of American Chemical Society.
132(26):8848-8849, 2010.
Chen, Y., Zhu, X.,, Zhang, X., Liu, B., and Huang, L. Nanoparticles Modified with Tumor-targeted scFv Deliver
siRNA and miRNA for Metastasis Therapy. Molecular Therapy 18:1650-1656, 2010.
Chen, Y., Bathula, S. R., Yang, Q., and Huang, L. Targeted Nanoparticles Deliver siRNA to Melanoma.
Journal of Investigative Dermatology. 130(12):2790-2798, 2010.
Bauman, J.A., Li, S.D., Yang, A., Huang, L. Kole, R. Anti-Tumor Activity of Splice-Switching Oligonucleotides.
Nucleic Acid Research, 38(22): 8348–8356, 2010.
Vasievich, E. A., Chen, W.C. and Huang, L. Enantiospecific Adjuvant Activity of Cationic Lipid DOTAP in
Cancer Vaccine. Cancer Immunology and Immunotherapy. 60(5):629-38, 2011.
Vasievich E.A. and Huang L. The suppressive tumor microenvironment: a challenge in cancer immunotherapy.
Mol. Pharm. 8(3):635-41, 2011.
Kim, S.K. and Huang, L. Nanoparticle delivery of a peptide targeting EGFR signaling. J. Contr. Rel, In press,
2011.
RESEARCH SUPPORT:
Active:
1. NIH 1R01CA129421-01A1 (P.I. Leaf Huang)
03/01/08 – 2/28/13
Title: Interaction of Cationic Lipids with Dendritic Cells
Aims: To study the molecular signaling events of cationic lipid in DC, and to design effective anticancer vaccine
for cervical cancer.
2. NIH 1R01CA129835-01A1 (P.I. Leaf Huang)
03/01/08 - 2/28/13
Title: LPD Nanoparticles in Anticancer Therapy
Aims: To design self-assembled nanoparticles for delivery of siRNA to lung cancer and metastasis. This project
concentrates on LPD nanoparticles only.
3. NIH R01CA149363-01 (PI: Leaf Huang)
04/01/10 – 03/30/15
Title: Novel Nanoparticles for siRNA Delivery
Aims: Nanoparticles containing a membrane/core structure will be manufactured. The core will be calcium
phosphate precipitate which dissolves in the acidic endosome to release the siRNA into the cytoplasm.
4. NIH 1U54CA151652-01 (PI for project 2: Leaf Huang, Program Leader: Joseph Desimone)
09/01/10 – 07/31/15
Title: Therapeutic Targeting of The RAS Pathway by Nanoparticle Delivery of siRNA
Aims: The project will explore specific siRNA targeting KRas and downstream elements as a therapeutic agent for KRas
driven human lung cancer. The emphasis is to deliver siRNA, alone or together with a chemotherapy drug, and
demonstrate therapeutic efficacy in a genetically engineered mouse model for the disease.
Pending:
None.
PHS 398/2590 (Rev. 09/04)
Continuation Format Page