Dawid G Nowak

Weill Cornell Medicine, Medicine, Faculty Member

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Dawid Nowak is Assistant Professor at Weill Cornell Medicine. The major research focus of his group is determining how mutational patterns in prostate cancer affect their evolutionary progression into invasive and metastatic malignancy after the period of indolence. Understanding how genomic alterations contribute to cancer evolution can help to explain mechanistically how tumor cells escape from focal primary disease, invade local sites and ultimately metastasize to distant sites.

Dawid Nowak is a cancer biologist by training, having received his PhD in Pharmacology and Physiology from the University of Bristol, UK. During his doctoral studies, he developed a series of novel technologies to investigate the signaling pathways that regulate the splicing of the key angiogenic regulator VEGF-A. He was a Post-doctoral Fellow at Cold Spring Harbor Laboratory where his research were focused on developing prostate cancer models that can better utilize information derived from human genomic analysis. In his post-doctoral work, he combined modeling strategies and single-cell sequencing to discover drivers of metastasis and to follow the evolution of genes at the level of Copy Number Alterations (CNA).

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Emory University

University of North Carolina at Chapel Hill

University of Washington

Sonal Brahmbhatt

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Utility of single cell genomics in diagnostic evaluation of prostate cancer

by Joan Alexander and Dawid G Nowak

A distinction between indolent and aggressive disease is a major challenge in diagnostics of pros... more A distinction between indolent and aggressive disease is a major challenge in diagnostics of prostate cancer. As genetic heterogeneity and complexity may influence clinical outcome, we have initiated studies on single tumor cell genomics. In this study, we demonstrate that sparse DNA sequencing of single-cell nuclei from prostate core biopsies is a rich source of quantitative parameters for evaluating neoplastic growth and aggressiveness. These include the presence of clonal populations, the phylogenetic structure of those populations, the degree of the complexity of copy-number changes in those populations, and measures of the proportion of cells with clonal copy-number signatures. The parameters all showed good correlation to the measure of prostatic malignancy, the Gleason score, derived from individual prostate biopsy tissue cores. Remarkably, a more accurate histopathologic measure of malignancy, the surgical Gleason score, agrees better with these genomic parameters of diagnostic biopsy than it does with the diagnostic Gleason score and related measures of diagnostic histopathology. This is highly relevant because primary treatment decisions are dependent upon the biopsy and not the surgical specimen. Thus, single-cell analysis has the potential to augment traditional core histopathology, improving both the objectivity and accuracy of risk assessment and inform treatment decisions.Significance: Genomic analysis of multiple individual cells harvested from prostate biopsies provides an in depth view of cell populations comprising a prostate neoplasm, yielding novel genomic measures with the potential to improve the accuracy of diagnosis and prognosis in prostate cancer.

Dawid G Nowak

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