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
Genomic Characterization of HIV-Associated Plasmablastic Lymphoma Identifies Pervasive Mutations in the JAK–STAT Pathway
Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma associated with immunodeficiency in the context of human immunodeficiency virus (HIV) infection or iatrogenic immunosuppression. While a rare disease in general, the incidence is dramatically increased in regions of the world with high HIV prevalence. The molecular pathogenesis of this disease is poorly characterized. Here, we defined the genomic features of PBL in a cohort of 110 patients from South Africa (15 by whole-exome sequencing and 95 by deep targeted sequencing). We identified recurrent mutations in genes of the JAK–STAT signaling pathway, including STAT3 (42%), JAK1 (14%), and SOCS1 (10%), leading to its constitutive activation. Moreover, 24% of cases harbored gain-of-function mutations in RAS family members (NRAS and KRAS). Comparative analysis with other B-cell malignancies uncovered PBL-specific somatic mutations and transcriptional programs. We also found recurrent copy number gains encompassing the CD44 gene (37%), which encodes for a cell surface receptor involved in lymphocyte activation and homing, and was found expressed at high levels in all tested cases, independent of genetic alterations. These findings have implications for the understanding of the pathogenesis of this disease and the development of personalized medicine approaches.