Research
Current Projects |
| Differential affinity and specificity of tandem calponin homology domains
Fletcher Laboratory Dept. of Bioengineering, University of California, Berkeley
Postdoc Advisor: Dr. Daniel Fletcher
Coming soon!
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| Interrogating macrophage-cancer interface using designed proteins
Fletcher Laboratory Dept. of Bioengineering, University of California, Berkeley
Postdoc Advisor: Dr. Daniel Fletcher
Cell-cell interfaces are fundamental to multi-cellular organisms and their
disruption has been linked to cancerogenesis, metastasis, and immune evasion.
The kinetic-segregation model proposes that the interface distance between two
cells established by a receptor-ligand pair can physically exclude repressive
signaling molecules with large extracellular domains and trigger activation.
This model has been studied for T cell receptor activation, but is predicted to
extend to other receptors.
We propose to use designed protein tools to
systematically study the predictions of the kinetic-segregation model in the
antigen-antibody-Fc receptor mediated interactions between tumors and macrophages.
Our goal is to understand how physical properties like size, shape, affinity,
orientation, and spacing of proteins work together at a cell-cell interface
for the proper antibody-mediated activation of macrophage phagocytosis of cancer cells.
The insights into tumor-macrophage interactions gained from this biophysical approach
may lead to the design of more effective antibody-based cancer therapeutics.
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Previous Projects
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Engineering Stem Cells an Antitumor Therapeutic Against Gliomas
Yang Laboratory, Dept. of Bioengineering, Stanford University, Spr 2010
Mentor: Dr. Fang Yang
Glioma patients have rather poor prognosis regardless of surgery, radiotherapy or chemotherapy.
It has been found that mesenchymal stem cells have a natural ability to migrate towards glioma cells in rat models.
Therefore, engineered stem cells show promise as a novel therapeutic platform for the treatment of malignant brain tumors.
Specifically, I tested to see if adipose derived stem cells, which are relatively easy to harvest from patients,
could be induced to migrate towards and kill rat PC-12 cells in a similar manner using in vitro trans-well assays.
Utilizing natural properties of stem cells and advantages of biomaterials to develop a modular therapeutic platform
for the treatment of malignant brain tumors.
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Engineering microRNAs for the Manipulation of Mammalian Cells
Smolke Laboratory,
Dept. of Bioengineering, Stanford University, Win 2010
Mentor: Dr. Christina Smolke, Yvonne Chen
MicroRNAs are non-coding RNAs that repress translation of their target protein.
Projects include: 1) engineering miRNAs capable of responding to the
presence specific nuclear proteins and 2) elucidating the characteristics
of inter-miRNA spacers that allows efficient processing of multiple miRNAs.
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Regulated Flux Balance Analysis of Host-Pathogen Interactions
Covert Laboratory,
Dept. of Bioengineering, Stanford University, Aut 2009
Mentor: Dr. Markus Covert
Host-pathogen systems emerge from the intricate interactions between
two organisms and result in more extensive networks than suggested by
studying the host or pathogen separately. Bacteriophage lambda infection
of E. coli is an is 1) a classic host-pathogen model and 2) relevant to
other systems. The process of incorporating a lambda phage component into
an regulated flux balance analysis (rFBA) model of E. coli to accurately reflect
phage impact on host E. coli metabolism will provide insight into phage
impact on E. coli metabolism, regulation between the
host and pathogen, and the nature of the ‘objective function’ for FBA models
involving multiple entities.
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ANTI–CANCER NANOPODS: Rational Design of an Oligoarginine Based Gene Delivery Vehicle Targeted to Hepatocarcinoma
Pun Laboratory,
Dept. of Bioengineering, University of Washington, 2008-2009
Mentors: Dr. Suzie Pun, Dr. Robert Burke
Liver cancer is one of the three deadliest cancers in the world and current treatments involve significant damage to healthy tissue.
Gene therapy, which aims to replace defective genes inside cells in order to
treat diseases, holds promise for treating liver cancer because of the various pathways it can exploit.
Non-viral materials have the potential to overcome safety and scalability limitations of viral vectors.
This project was to design, construct, and test novel peptide-based materials
specifically targeted to hepatocarcinoma for use as systemically administered gene therapy vectors.
The peptide material consists of a nonaarginine DNA condensing component linked to a
hepatocarcinoma-specific binding peptide (seq: FQHPSFI) to form an anticancer “nanopod†protects and guides the DNA therapeutic.
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MOLECULAR SWISS ARMY KNIFE: Designing Multifunctional Non-viral Vehicles for Gene Delivery to Neurons
Pun Laboratory,
Dept. of Bioengineering, University of Washington, 2007-2008
Mentors: Dr. Suzie Pun, Dr. Jamie Bergen
Gene therapy promises to treat neurological disorders,
such as Alzheimer's and Huntington’s disease, that currently have limited or
no available treatment.
The particular non-viral vehicles used in this experiment are polyplexes,
or polymer/DNA complexes.
The major challenge faced by these materials is the inefficiency of polyplexes at
overcoming barriers to gene delivery, especially in non-dividing cell types such as neurons.
Intracellular barriers to nuclear delivery of foreign DNA include targeting,
uptake, endosomal escape, retrograde transport, and nuclear localization.
This project focuses on attaching peptide ligands that target barriers to the surface
of polyplexes to increase DNA delivery efficiency.
Specifically, a peptide ligand based on the human papillomavirus minor capsid protein L2,
which is hypothesized to have endosomal escape as well as retrograde transport capabilities,
was conjugated to polyethylenimine.
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HIFU Reflection Lesion Characterization
Vaezy Laboratory, Dept. of Bioengineering, University of Washington, 2005
Mentors: Dr. Shahram Vaezy, Dr. Jinfei Yu
High Intensity Focused Ultrasound (HIFU) is a medical therapy modality for non-invasive,
capable of extracorporeal treatment of internal bleeding and tumors.
The energy delivered by a HIFU transducer can be amplified by reflecting the ultrasound beam
from post-focal regions back towards the focus.
We studied the volume of the lesions produced in turkey breast, by HIFU,
with and without an ultrasound reflector in order to more fully understand
how to utilize the reflections. |
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