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Cancer Genomics in the Brain

Published in , 1900

How do we leverage the increasing amount of genetics and genomics data to better diagnose, classify and treat brain tumors? We investigated the ancestry-based genomic signature differences in patients with malignant brain tumors and the implications of clinical trial designs in these incurable diseases¹. We also looked at various biomarkers that can non-invasively but accurately diagnose, prognose and classify brain tumors including viral infection history, hematological parameters and immune system parameters. These studies collectively contributed to personalized and minimally-invasive diagnostic processes of malignant brain tumors in the future and point to more effective patient stratification strategies for clinical trials.

To Breathe or Not to Breathe - The Secret of Anaerobic Pathogens

Published in , 1900

A longstanding mystery in the anaerobic bacteria Listeria Monocytogenes, one of the deadliest foodborne pathogen, is the conflict between their broken oxygen-dependent cellular respiration cycle and their dependence on oxygen for intracellular replication. In fact many other anaerobic bacteria can utilize alternative electron transfer mechanisms to survive in the absence of oxygen¹. We investigated the mechanisms behind such discrepancy and pinpointed an interesting chemical imbalance in the microbe in the absence of oxygen. The resulted was highlighted by the editors as one of the 90 spotlight papers out of the 2000 published papers that year. Our result pointed a promising therapeutic strategy to mitigate infections by these anaerobic microbes.

Digital Health for Psychiatric Disorders

Published in , 1900

As digital technologies permeate every aspect of human lives, they bring both positive and negative impacts of psychiatric disorders and mental health. While there have been a plethora of evidence on the increasing incidence of psychitriac disorders due to digital technologies, there are fewer studies that focus on the opportunities that technology can also open for better psychitric support. We performed several studies on how the digital era can be leveraged to positively addresses many challenges of psychiatric disorders including stigma, peer support and access in low-and-middle income countries.

Biophysically-detailed Recurrent Neural Network Model of the Entire Nervous System of C. elegans

While AI is rapidly developing and demonstrating impressive performance on wide range of tasks, it is unclear that traditional AI models will ever get us to WBE due to the dramatic simplification of biophysical details of neurons compared to the real brain. Incorporating the biophysical details such as ion channel mechanisms, morphology and neurotransmitters will both allow more faithful representation of the nervous system digitally and hold the potential for energy/data-efficient AI in the future. Leveraging the recent breakthrough to train large recurrent biophysical networks ¹, I am building towards the first closed-loop reproducible biophysically detailed nervous system model of C. elegans fitted to real calcium and behavior recording.

Dual-View SCAPE for Whole Nervous System Calcium Imaging of C. elegans during Free Behaviors

In order to replicate the whole brain in silico, neural recording needs to be high resolution (single-neuron), high-speed, large field of view to cover the entire nervous system and should ideally be done during naturalistic behaviors. To date, a microscope that satisifies all of these requirements do not exist even for C. elegans. However, promising approaches such as Oblique Planar Light Sheet Microscope (OPM) offers paths to reach the goal. One of the best performing OPMs is the SCAPE microscope ¹. However it lacks sufficient axial resolution to fully resolve every single neuron in C. elegans. I am building the world’s first microscope that can enable true full nervous system high speed recording during behaviors by giving dual-view capability to SCAPE, which can be converted to near isotropic resolution through fusion deconvolution processing. This technology will give us unbiased comprehensive neural activity datasets that will be critical for WBE.

Worm Expansion Sequencing (WormSeq) as a Scalable Tool for Molecularly Annotated Connectome (MAC)

Expansion Sequencing (ExSeq) ¹ is an innovative technology that can reveal molecular signatures at an unprescendented details and complexity. It has subcellular nanoscale resolution, retains the spatial information and has high multiplexed capabilities that allow interrogation of hundreds and thousands of genes together with other information modalities such as lipid, sugar, proteins, all in one biological context. Its combination with the recently published Expansion Microscopy-based connectomics protocol will greatly enrich the information content of traditional connectome. In fact, molecularly annotated connectome (MAC) has been long thought of as a critical missing pieces for understanding how the wiring diagram gives rise to behaviors. I am currently developing the protocol to generate the world’s first MAC. This project, which I call WormSeq, will form the necessary building block for simulating the C. elegans nervous system with high biological fidelity.

Teaching experience 2

Workshop, University 1, Department, 2015

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GFLI@MIT

, , 1900

This is a description of a teaching experience. You can use markdown like any other post.