I am a current junior at Caltech studying physics with a minor in computer science. My current research interests involve ultrasound and MRI imaging and therapy, under the mentorship of Mikhail Shapiro and Mohamad Abedi in the Shapiro Laboratory. Prior to Caltech, I worked in the Gruenert Lab at UCSF on stem cell research and modification through CRISPR/Cas9 technologies. I aspire to pursue a career as a physician-scientist, involving research at the intersection of multiple fundamental sciences for real-world applications.
Cancer Therapy Using Engineered Probiotics
using ultrasound to actuate bacterial cellular activity in-vivo through engineering thermally excitable, tumor homing probiotics
I am interested in developing a prokaryotic cellular therapy for solid tumors because bacteria have previously been shown to be naturally tumor-homing agents. However, due to the potential of microbes to cause off-tumor toxicity, our goal was to engineer them to specifically activate when inside the tumor.
To accomplish this, we combined therapeutic ultrasound technology, which can heat tissues deep within the body with millimeter precision, with the ability to engineer bacteria to sense mild elevations in temperature. Together, these technologies would enable us to utilize a probiotic strain of E. coli to express therapeutic biologics upon thermal actuation specifically in the tumor. This presents a novel, non-invasive technique to control bacterial cell behavior in-vivo. To confer thermal sensitivity in E. coli, we are designing genetic circuits dependent on transcriptional control elements that are responsive to changes temperature.
Ultimately, these engineered probiotics can be used as a therapeutic tool in the treatment of solid tumors, where clinical focused ultrasound can localize the expression of cytotoxic therapeutic agents to within cancerous legions, avoiding systemic side effects.
Improving the Safety of CAR T-Cell Immunotherapy
developing novel gene-regulatory tools to modulator T-cell gene expression and activity in a thermally sensitive manner with large fold changes
My colleagues and I are working on taking heat-sensitive gene regulatory elements and functionalizing them for transcriptional control of mammalian cell expression in a temperature-sensitive manner. Successful translation of this technology into eukaryotic cells could be used in conjunction with a multitude of common gene-expression technologies, such as Gal4-UAS and CRISPR-dCas9 systems. The result is robust thermal actuation of mammalian cells, such as those used in CAR T-cell and other immunotherapies, which can prevent on-target, off-tumor damage of healthy tissue when used in conjunction with focused ultrasound.
Looking at Hypoxia Deep Within the Body
manipulation of cellular contrast with DW-MRI imaging in response to external stimuli to track cellular movement in the body with millimeter precision
I am functionalizing a genetically encodable MRI contrast agent as an in-vivo hypoxia sensor for glioblastoma cells. Many drugs that are being developed for the treatment of solid tumors are sensitive to environmental oxygen levels, which can present challenges in making the drugs effective within hypoxic tumor microenvironments. The effect of local hypoxia is often difficult to quantify because of the inability to easily measure oxygen levels within a solid tumor. To address this limitation, we are engineering a cell-based hypoxia sensor for MRI, a widely used imaging modality, such that the strength of the MRI signal could be used to estimate the oxygen level in the cellular environment.
Ideally, these engineered glioblastoma cells can be used as a research tool in better understanding the complex tumor microenvironment in a noninvasive manner, and also assessing anti-angiogenic and anti-vasculogenic therapies as a function of oxygen levels in the tumor.
The small object allocator is a spin on your usual
malloc() implementation for optimized memory management when dealing with small objects.
It has been well-characterized that repeated sequences in a plasmid DNA sequence can result in excision of plasmid components within certain bacteria. This program analyzes plasmid DNA sequences to warn of potential sites of homology and therefore DNA excision.