Our

Research

Research at the Rabadan Lab

Our main scientific interests lie in modeling and understanding the dynamics of biological systems through the lens of genomics. We are a very interdisciplinary team of mathematicians, physicists, engineers, biologists, and medical doctors with a common goal of solving pressing medical problems. We are currently focusing our work on:

  • Cancer. Genomic technologies provide an extraordinary opportunity to identify mutations that contribute to the development of tumors. We are mapping the evolution of cancers and uncovering the mechanisms of response or lack of response to multiple therapies. We work with clinicians and experimentalists all around the world.

  • Infectious diseases. Evolution is a dynamic process that shapes genomes. Our team at Columbia is developing algorithms to analyze genomic data, with a view to understanding the molecular biology, population genetics, phylogeny, and epidemiology of viruses. We are interested in the emergence of infectious diseases, pandemics and uncovering the mechanisms of adaptation of viruses to humans.

  • Electronic Health Records. Clinical databases constitute a rich and complex source of raw data. We are using the power of statistics and computers to tease out important clinical patterns in these diverse, important datasets. Combining molecular and clinical data illuminates some of the mechanisms underlying complex diseases.

In particular, we develop mathematical, statistical, and computational approaches, which cover the analysis of high throughput data right through to the altogether more abstract identification of global patterns in evolutionary processes. Learn more about the Rabadan Lab and the three main global questions that we are addressing.

Research Projects

THE RABADAN LAB THE RABADAN LAB

Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker

Macrophages are the most common infiltrating immune cells in gliomas and play a wide variety of pro-tumor and anti-tumor roles. However, the different subpopulations of macrophages and their effects on the tumor microenvironment remain poorly understood. We combined new and previously published single-cell RNA-seq data from 98,015 single cells from a total of 66 gliomas to profile 19,331 individual macrophages. Unsupervised clustering revealed a pro-tumor subpopulation of bone marrow-derived macrophages characterized by the scavenger receptor MARCO, which is almost exclusively found in IDH1-wild-type glioblastomas. Previous studies have implicated MARCO as an unfavorable marker in melanoma and non-small cell lung cancer; here, we find that bulk MARCO expression is associated with worse prognosis and mesenchymal subtype. Furthermore, MARCO expression is significantly altered over the course of treatment with anti-PD1 checkpoint inhibitors in a response-dependent manner, which we validate with immunofluorescence imaging. These findings illustrate a novel macrophage subpopulation that drives tumor progression in glioblastomas and suggest potential therapeutic targets to prevent their recruitment.

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