[JaP1]
Gang Han
The Molecular Foundry,
Lawrence Berkeley National Laboratory,
One Cyclotron Road, Mail Stop: 67R4110,
Berkeley, CA 94720
Office: (510) 486-7874
Cell:(510) 542-7252
E-mail:
Education and Professional Training
Postdoctoral Fellow Lawrence Berkeley National Laboratory Aug. 2007- Present
(Jointly in Biological and Inorganic Nanostructure facilities at The Molecular Foundry, LBNL, Berkeley CA)
Visiting Postdoc, University of Chicago Jan. 2008 - Feb. 2008.
Ph.D. in Chemistry University of Massachusetts, Amherst Aug. 2002 - Aug. 2007
M. S. in Inorganic Chemistry Nanjing University, China 1999 - 2002
B. S. in Chemistry Nanjing University, China 1995 - 1999
Professional Experience
Postdoc Fellow at The molecular foundry, LBNL, Berkeley, CA Aug. 2007 - Present
Independent reviewer for Soft Matter, and the Journal of Material Chemistry
Research Assistant at the University of Massachusetts-Amherst, Amherst, MA 2003 - 2007
Teaching Assistant, Organic Chemistry 261 at the University of Massachusetts-Amherst, Amherst, MA Jan.-May. 2004
Teaching Assistant, General Chemistry Laboratory 111 and 112 at the University of Massachusetts-Amherst, Amherst, MA 2002-2003
Teaching Assistant, Physical Chemistry Laboratory at Nanjing University, China 2000-2001
Awards and Honors
Selected as 2006-2007 University Outstanding Graduate Student Fellowship (one awarded per department), the University of Massachusetts, Amherst
Named as a 2006 Invitrogen Fellow (Gordon Conference, Macromolecular Organization & Cell Function)
Chosen to present at the first annual NIH National Outstanding Graduate Student Research Festival (One of only 250 senior graduate students selected across the U.S.) Aug. 2006
Awarded the 2006 William E. McEwen Outstanding Chemistry Graduate Student Award
Professional Affiliation
Full membership in Sigma Xi, The Scientific Research Society
Member of the Materials Research Society
Member of the American Association for the Advancement of Science (AAAS)
Member of the American Chemical Society since 2002.
Former Member of the Chemistry-Biology Interface Training Program (CBI)
the University of Massachusetts Amherst.
Publications:
The Molecular Foundry, LBNL:
30. Wu,S. , Han, G.;(Co-first Authorship) Milliron, D.J.; Aloni, S.; Altoe, V.; Talapin, D.V.; Cohen, B. E.;, and Schuck, P.J. “ Non-blinking and photostable upconverted luminescence from single lanthanide-doped nanocrystals. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(27), 10917- 10921, (reported in MRS Bulletin,34(8) 557, August 2009 and LBNL news)
29. Han, G.; Ajo-Franklin, C.; Mokari, T.; Cohen, B.E. “Caged Quantum dots” Journal of the American Chemical Society.,2008, 130 (47), 15811–15813, (reported in Chemical & Engineering News, 86(46), November 17, 2008)
28. Chan, E. M.; Xu, C.; Mao, A.; Han, G.; Owen, J.S.; Cohen, B.E.; and Milliron, D.J.
“Reproducible, High-Throughput Synthesis of Colloidal Nanocrystals for Optimization in Multidimensional Parameter Space.” Nano letters In Press
27. Liang, X.; Chen, T.; Jung, Y.; Miyamoto, Y.; Han, G.; Cabrini, S.; Ma B.; and Olynick O.L.
“Nanoimprint-Induced Molecular Stacking and Pattern Stabilization in a Solution-Processed Subphthalocyanine Film” ACS Nano In Press
University of Massachusetts-Amherst:
26. Kim, B.; Han, G.; Toley, B. J.; Kim, C.-K.; Rotello, V. M.; Forbes, N. S. “Tuning payload delivery in tumour cylindroids using gold nanoparticles.” Nature Nanotechnology. In Press
25.Jordan, B. J.; Hong, R.; Han, G.; Rana, S.; Rotello, V. M. "Modulation of enzyme–substrate selectivity using tetraethylene glycol functionalized gold nanoparticles" Nanotechnology, 2009, 20, 434004.
24. Ghosh, P. S.; Kim, C.-K.; Han, G.; Forbes, N. S.; Rotello, V. M. “Efficient Gene Delivery Vectors by Tuning the Surface Charge Density of Amino Acid- Functionalized Gold Nanoparticles” ACS Nano, 2008, 2(11)2213..
23. Chompoosor, A.; Han, G.; Rotello, V. M. "Charge Dependence of Ligand Release and Monolayer Stability of Gold Nanoparticles by Biogenic Thiols" Bioconjugate Chem., 2008, 19, 1342-1345.
22. Ghosh, P; Han, G; De, M; Rotello, VM .”Gold nanoparticles in delivery applications.”
Advanced drug delivery reviews 2008, 60(11) 1307-1315.
21. Han, G; Ghosh, P; Rotello, VM. “Multi-functional gold nanoparticles for drug delivery”
Bio-applications of nanoparticles 2007,: 620, 48-56
20. Ghosh, PS.; Han, G.; Erdogan B.; Rotello, VM. “Binding of nanoparticle receptors to peptide alpha-helices using amino acid-functionalized nanoparticles” Journal of peptide science 2008, 14(2) 134-138
19. Leroueil, P ; Berry, SA.; Duthie, K.; Han, G.; Rotello, VM.; McNerny, DQ.; Baker, JR. Jr., Orr,BG.; and Banaszak Holl, MM.“Wide varieties of cationic nanoparticles induce defects in supported lipid bilayers”
Nano letters 2008 , 8(2) 420-424
18. Han, G., Ghosh, P.; De, M, Rotello V. M. “Drug and gene delivery using gold nanoparticles .” NanoBioTechnology 2007, 3(1)1551.
17. Ghosh, PS.; Han, G.; Erdogan B.; Rotello, VM. “Nanoparticles featuring amino acid-functionalized side chains as DNA receptors” Chemical Biology & Drug Design 2007, 70 (1) 13-18.
16. Book Chapter: Han, G., Ghosh, P.; Rotello V. M. “Multi-Functional gold nanoparticles for drug delivery.” In the book “ Bio-applications of nanoparticles” edited by Dr. Warren Chan.
15. Srivastava, S.; Samanta, B.; Arumugam, p.; Han, G. Rotello, V. M. “Influence of DNA on Spacing and Magnetic Properties of Iron Platinum (Fe-Pt) Nanoparticles Journal of Material chemistry. 2007,17(1) 52-55.
14. Han, G., Ghosh, P.; Rotello V. M. “Functionalized gold nanoparticles for drug delivery.” Nanomedicine 2007, 2(1) 113-123.
13. Nakade, H.; Jordan, B.J.; Xu, H.; Han, G.; Srivastava, S.; Arvizo, R.R.; Rotello, V.M. “Supramolecular Chirality Induction: Discrete Self-Assembly of Specific Hydrogen Bonding Dyad” Journal of the American Chemical Society 2006, 128 (46), 14924-14929.
12. Vanderpuije, B.; Han, G.; Rotello, V.M.; Vachet, R.W. “Mixed Monolayer-Protected Gold Nanoclusters as Selective Peptide Extraction Agents for MALDI-MS Analysis” Analytical Chemistry 2006, 78 (15), 5491-5496
11.Goodman, C.M.; Chari, N.S.; Han, G.; Hong R.; Ghosh, P.; Rotello, V.M. “DNA-binding by Functionalized Gold Nanoparticles: Mechanism and Structural Requirements” Chemical Biology and Drug Design,. 2006, 67 (4), 297-304.
10. Han, G.; You, C.-C; Kim, B.J.; Turingan, R.S; Forbes, N.S.; Martin, C.T.; Rotello, V.M. “Light-Regulated Release of DNA and Its Delivery to Nuclei by Means of Photolabile Gold Nanoparticles.” Angewandte Chemie International Edition,. 2006, 45 (19), 3165-3169.(reported by NCI and Nature Materials)
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9. Han, G; Martin, C.T.; Rotello, V.M. “Stability of gold nanoparticle-bound DNA toward biological, physical, and chemical agents.” Chemical Biology and Drug Design, 2006, 67 (1), 78-82. (Editor’s highlights)
8. Hong, R; Han, G; Fernandez, J.M.; Kim, B.J.; Forbes, N.S.; Rotello, V.M. “Glutathione-mediated delivery and release using monolayer protected nanoparticle carriers.” Journal of the American Chemical Society, 2006, 128 (4), 1078-1079.
7. Han, G.; Chari, N.S.; Verma, A.; Hong, R.; Martin, C.T.; Rotello, V.M. “Controlled recovery of the transcription of nanoparticle-bound DNA by intracellular concentrations of glutathione.” Bioconjugate Chemistry, 2005, 16 (6), 1356-1359. (#16 Most-Accessed Articles: October-December, 2005)
6. You, C.-C.; De, M.; Han, G.; Rotello, V.M. “Tunable inhibition and denaturation of alpha-chymotrypsin with amino acid-functionalized gold nanoparticles.” Journal of the American Chemical Society, 2005, 127(37), 12873-12881.
Nanjing University:
5. Chen, G.; Ou, S.J.; Bai, Z.P.; Han, G.; Duan, C.Y. “Synthesis, crystal structure and electrochemistry of biferrocene palladium complex” Chinese Journal of Inorganic Chemistry, 2003,19 (5): 501-505.
4. Han, G.; Guo, D.; Duan, C.Y.; Mo, H Meng, Q.J. “Self-assembly of a novel mixed-valence tetranuclear molecular square [(Fe3FeL2)-Fe-II-L-III(HL)(2)](3+) and [M(HL)](4)(4+) squares (M = Ni, Zn and Cd) {H2L = bis(2-acetylpyridine) thiocarbazone}” New Journal of Chemistry, 2002, 26 (10): 1371-1377.
3. Guo, D.; Han, G.; Duan, C.Y., Pang, K.L.; Meng, Q.J. “Novel ferrocene-containing helical triangular macrocycle achieved via an exchange reaction” Chemical Communications, 2002, 10, 1096-1097.
2. Fang, C.J.; Duan, C.Y.; He, C; Han, G.; Meng, Q.J. “A supramolecular analog of cyclohexane sustained by aromatic C-H center dot center dot center dot pi interactions between ferrocene moieties: molecular packing of ferrocene-containing thiosemicarbazato metal complexes” New Journal of Chemistry, 2000, 24 (9): 697-701.
1. Fang, C.J.; Han, G.; Liu, Y.J.; Duan, C.Y.; Meng, Q.J. “Acetylferrocene thiosemicarbazone” Acta Crystallographica Section C-Crystal Structure Communications, 1999, 55,2058-2060.
Presentations:
16.Mar. 2010, Oral Presentation, American Chemical San Francisco, CA
15. Nov. 2009, Oral Presentation, Materials Research Society, Boston, MA
14. Nov. 11, 2008, Oral Presentation, Molecular Foundry (TMF) & the National Center for Electron Microscopy (NCEM) users’ meeting at Lawrence Berkeley National Laboratory
13. March 2007, Poster Presentation, American Chemical Society, Chicago, IL. “Charge effects on gold nanoparticle-based drug delivery” Han, G.; Kim, B.J.; Forbes, N.S.; Martin, C.T.; Rotello, V.M in Colloid Division.
12.March, 2007, Oral Presentation, American Chemical Society, Chicago, IL. “DNA/Drug delivery into cells using multifunctional gold nanoparticles” Han, G.; Chompoosor, A.; Kim, B.J.; Forbes, N.S.; Martin, C.T.; Rotello, V.M in Colloid Division.
11. November, 2006 Poster Presentation in National Nano Engineering Conference (NNEC) at Boston .
10. October, 2006 Poster Presentation in NIH Campus , Bethesda, MD. USA (First Annual National Graduate Research Festival)
9. September, 2006 Poster Presentation in Center for Hierarchical Manufacturing (CHM) UMass-Amherst.
8. September,2006: Oral Presentation in 16th Annual Research Symposium, Chemistry department, UMass-Amherst
7. August, 2006: poster presentation in Gordon Conference, Macromolecular Organization & Cell Function.
6. March, 2006: American Chemical Society, Atlanta, GA. “Light-regulated DNA transcription and delivery using photolabile gold nanoparticles.” Han, G.; You, C.-C; Kim, B.J.; Forbes, N.S.; Martin, C.T.; Rotello, V.M. Oral presentation in Organic Division.
5. March, 2006: American Chemical Society, Atlanta, GA. “Glutathione-mediated drug release using monolayer protected nanoparticle carriers.” Han, G.; Hong, R.; Fernandez, J.; Kim, B.J.; Forbes, N.S.; Martin, C.T.; Rotello, V.M. Poster presentation in Division of Colloid and Surface Chemistry.
4. March, 2006: The Molecular & Cellular Biology Program (MCB) at UMass, Amherst Retreat “DNA recognition and delivery using functional gold nanoparticles” Han, G.; Martin, C.T.; Rotello, V.M. Poster presentation.
3. August, 2005: American Chemical Society, Washington, D.C.” DNA recognition and delivery using nanoparticle scaffolds.” Han, G.; Erdogan, B.; Goodman, C.M.; Sandhu, K.K.; Martin, C.T..; Rotello, V.M. Poster presentation in Organic Division.
2. January, 2005: Chalk talk of Chemistry-Biology Interface Training Program (CBI) University of Massachusetts Amherst. Oral presentation.
1.May, 2004: Researchfest of chemistry department , University of Massachusetts Amherst. .” DNA binding and delivery using gold nanoparticles.” Han, G.; Martin, C.T.; Rotello, V.M. Poster presentation.
Other co-authored presentations:
4. March, 2006: American Chemical Society, Atlanta, GA. “Superquenching of conjugated polymers by gold nanoparticles and recovery of fluorescence by DNA for sensing applications.” Krovi, S.A.; Erdogan, B.; Han, G.; Kim, I.B.; Bunz, U.H.F.; Rotello, V.M. Poster presentation in Polymer division.
3. March, 2006: American Chemical Society, Atlanta, GA. “DNA sensing using nanoparticle-based receptors.” Erdogan, B.; Krovi, S.A.; Han, G.; Kim, I.B.; Bunz, U.H.F.; Rotello, V.M. Oral presentation in PMSE division.
2. August, 2005: American Chemical Society, Washington, D.C.” Tunable inhibition and denaturation of -chymotrypsin with amino acid-functionalized gold nanoparticles. ” You, C.C.; De, M.; Han, G.; Rotello, V. M.. Poster presentation in Organic Division.
1. August, 2005: American Chemical Society, Washington, D.C.” Supramolecular helical induction using specific hydrogen bonded dyads.” Nakade, H.; Jordan, B.J.; Xu, H.; Han, G.; Srivastava, S.; Rotello, V.M. Poster presentation in Organic Division.
Small[JaP2] and Bright[JaP3]: Application of Specialized Optical [JaP4]Nanomaterials
A research statement by Gang Han
My main research interest, both short and long term, is to lead a research team that focuses on both small and bright, that is, the development of smart materials featuring optical properties at nanoscale to be used for biological and energy related applications. In particular, I am most interested in lanthanide doped nanoparticles: from obtaining a fundamental understanding of their unusual properties (e.g. upconverting, quantum cutting, magnetic behavior, etc.), to their applications in drug delivery, biological imaging, chemical and biological sensing, and even in photovoltaic devices. With these important goals in mind, I propose to develop a synergetic research program using multidisciplinary types of knowledge, such as synthetic chemistry, materials science, biochemistry, and cell biology, among others. This research will be on, but not limited to, the following two intimately connected topics:
1)I will first carry out the synthesis of nanomaterials and study their unique optical and electronic properties. I will then explore their applications in a biological system, such as in drug delivery and ultrahigh resolution nanoscale imaging.
2)I will utilize biological systems to create nanomaterials with biological non-existing properties: an RNA apatmer as the selective template and catalyst for the better growth of specialized optical nanomaterials[JaP5].
The success of my research program will not only provide new tools for controlling photochemical processes in chemistry and biology, more accurately probing the dynamics of biomolecular motions and reactions, it will also lead to an entirely new field for offering unnatural properties [JaP6]to biological systems.
Nanomaterials Synthesis and Applications in Biology
My research will lead to the creation of various functionalized nanomaterials through my [JaP7]synthesis background. As a graduate student, I synthesized surface modified gold nanoparticles and group II-VI semiconductor quantum dots for DNA binding with an eye towards a variety of applications in the health sciences. During my postdoctoral research, I have functionalized group III-V semicondutor nanoparticles and heterostructural core/shell nanorods in order to create new types of imaging probes. My most recent focus has been that of developing a new type of lanthanide doped upconverting nanoparticles for cell imaging. Among all of these nanomaterials, lanthanide doped nanoparticles will be the first components to be explored in my future research group. The reason for this is that, since they exhibit many unusual properties, including upconverting, quantum cutting and magnetic properties, the current experimental and theoretical understanding of such materials is sorely lacking. [JaP8]
Initially, I will follow up on my previous research experience by exploring the controlled synthesis and functionalization of lanthanide doped upconverting nanoparticles for a variety of biological applications. These nanoparticles absorb two photons in the near infrared (NIR) and emit at shorter wavelengths in the visible or NIR and are exceptionally valuable in the quest for biological applications, as: (1) compared to semiconductor materials, rare earth core materials are much less toxic since rare earth based fertilizers have been used to improve crop yield; (2) NIR radiation is significantly less damaging to cells, scatters less and allows for deeper tissue penetration; (3) the unique upconverting process allows no spectral overlap to occur in regard to most exogenous and endogenous fluorophores, providing virtually zero [JaP9]autofluorescent background; (4) they exhibit no blinking behavior, are exceptionally photostable, and resist photobleaching for an extremely long while.
The adoption of upconverting nanoparticles into biological systems can generate essentially unlimited applications. To follow are two applications in drug delivery and bioimaging, respectively, that I feel should be listed here.
A) Light-controlled DNA/drug delivery using ultraviolet (UV) emitted UCNPs
As a highly orthogonal external stimulus, light enjoys wide usage in materials science, chemistry, biology and drug delivery systems. It possesses the unique ability to control photochemical reactions in a spatiotemporal manner. Versatile photosensitive molecules have been designed in this regard. For example, biologically active molecules can be modified with photosensitive groups to be essentially bio-inert, and can then be reactivated by photointervention. Taking advantage of such a strategy, during my graduate studies, I developed photolabile gold nanoparticles as a UV light controlled RNA polymerase switch and DNA delivery system. Similarly, during my postdoctoral research, I also worked with Dr. Cohen to develop a new type of imaging probe -- Caged Quantum dots that remain dark until they are turned on by pulses of UV light.
However, one particular problem that yet remains for such caged systems and most of the other photosensitive molecules is their need for UV light to induce photochemical reactions. Such types of short wavelength light have an undesirable phototoxic effect on living systems. Moreover, the depth of tissue penetration using these types of light [JaP10]is also quite limited. To date, a couple of approaches have been designed in this regard: 1) A two-photon or multi-photon excitation by near infrared (NIR) light and 2) A bioluminescence resonance energy transfer (BRET). However, the first approach requires delicately designed molecules that have very high two-photon cross sections. Additionally, high frequency a laser source is needed to achieve the near coincident absorption of two or more infrared (IR) photons here. In the second approach, the energy initiated from the donor protein-mediated chemical reaction, and then transferred to the proximate emitters, can be used to uncage the targeted molecules. However, the use of a foreign protein and a foreign enzyme substrate will lead to an immunogenic problem and can alter the biological system as it is being studied. [JaP11]
To overcome this obstacle, I propose to synthesize and use lanthanide doped nanoparticles, which possess strong emission levels at the UV region. They will be particularly suitable for the photolysis of photolabile groups within the biological systems in a remote control fashion since: (1) Due to their long lifetime real electronic excitation states, they can much more effectively adsorb and will require much lower intensities of NIR light than conventional multi-photon excited molecules. (2) They are exceptionally photostable; (3) Together with ligands, which [JaP12]can render them biocampatiable and targeting with [JaP13]disease locations, UCNPs can further be easily modified with photolabile molecules, allowing the upconverted UV light to trigger photochemical reactions in situ.
NaYF4, doped with Yb and Tm (NaYF4, Yb, Tm), will be the first UCNP used to investigate this concept. NaYF4, Yb, Tm has been considered to be one of the most efficient UCNPs, possessing a relatively intense upconverting emission level in the UV-region. For example, as shown in figure 2, I will conjugate the drug or DNA molecules with UCNPs via a photosensitive linker. Upon being targeted and endocytosised into the tumor cells, the deep penetrated 980 nm NIR light can be upconverted into the [JaP14]UV light by use of the UCNPs; such energy will then be transferred to the surrounding photolabile group , resulting in their breakage and followed by the drug/DNA payload release.
I will then use a combinatorial means to construct a nanostructure library in order to improve the upconverting emission at an appropriate region by systemically adjusting several factors that are responsible for the efficiency and wavelength of the upconverting emissions.These factors include the host matrix, the dopant [JaP15]compositions, the lattice structure, the ratios of the absorbers and emitters, as well as the inorganic-inorganic and organic-inorganic interfaces.
The ultraviolet (UV) emitted by the UCNPs offers a new tool for controlling most of the UV-sensitive photochemical processes in a biological friendly manner. In addition to drug delivery, their uses can be extended into many chemical and biological applications, such as controlling biochemical reactions in microfluidic channels, in situ cross-link DNA or proteins, and advanced imaging techniques.
B) Measurement of nanometer distances using multicolor UCNPs.
While the multicolor imaging technique has become increasingly routine in biology, nanomaterials with fluorescence emission tunabilities, such as semiconductor quantum dots, have enjoyed an increasing amount of attention as novel imaging probes. Their excellent photostability and single wavelength excitation allows them to eliminate chromatic aberration and color registration, in that we can obtain nanometer distance-measurement accuracy for the investigation of dynamics and supramolecular organization of biomolecules at single molecular level using conventional far-field stage-scanning confocal microscopy. However, there are two problems that still limit their usage: (1) the intrinsic cellular autofluorescent background signals in biological systems are a common problem for most of these Stock luminescence probes. (2) they have time-dependent emission that goes on and off, in other words, a “blinking” problem.