Jason PITT

Cancer is a disease with multifactorial etiology. Environment, lifestyle, and genetics are well-known mediators of oncogenic cellular transformation. However – with respect to individual malignancies – the relative contributions of these factors are difficult to discern and require knowledge derived from massive, multivariate datasets.

jason.j.pitt@nus.edu.sg

Biosketch

Cancer is a disease with multifactorial etiology. Environment, lifestyle, and genetics are well-known mediators of oncogenic cellular transformation. However – with respect to individual malignancies – the relative contributions of these factors are difficult to discern and require knowledge derived from massive, multivariate datasets. Accordingly, the Pitt laboratory’s research program has two major aims:

1) the development of state-of-the-art software to facilitate data-intensive genomic analyses; and

2) the integration of inherited genetic variation, acquired mutations, and epidemiology to better understand cancer susceptibility and tumorigenesis. Using data science to unravel cancer’s origins can ultimately sharpen screening, early detection, and prophylactic treatment programs that are crucial to precision oncology.

Special Fellow, Cancer Science Institute of Singapore, NUS

Year(s) Degree (if applicable) Institute
2017 Ph.D. University of Chicago, Chicago, IL, USA
2009 B.A. Gustavus Adolphus College, St. Peter, MN, USA
2018 – Present Special Fellow, Cancer Science Institute of Singapore, NUS
2009 – 2011 Post-baccalaureate Fellow, Genetics Branch, National Cancer Institute, USA
2016 Charles J. Epstein Trainee Award for Excellence in Human Genetics Research – Finalist (American Society of Human Genetics)
2012 Partners in International Research (PIRE) Fellow (National Science Foundation)
2011-2014 Genetics and Regulation Training Grant recipient (University of Chicago)
2009 Rupert Anderson Award for Research (Gustavus Adolphus College)
2008 Presidential Research Grant (Gustavus Adolphus College)
2007-2008 Mayo Clinic Scholars Program

Research

The world is an ecosystem flooded with data. Tech giants such as Google, Amazon, and Facebook have capitalized on this resource by transforming torrential data streams into actionable intelligence. Advances in biotechnology have fostered a similar data niche in cancer genomics, which offers considerable scientific returns to those able to exploit it. As such, our laboratory develops software that enables cancer genome analyses to be performed at scale. These tools include SwiftSeq (https://github.com/PittGenomics/SwiftSeq), a highly-parallel computational workflow for processing DNA sequencing data on clusters, supercomputers, and clouds. In an effort to further increase throughput and minimize expenditures, some of our continued work emphasizes cost profiling and optimization of genomic workflows on commercial cloud platforms. Processing, however, is only one aspect of data-driven science. We are also constructing novel analytical tools that facilitate quick and efficient interrogation of structured genomic data.

Importantly, the aforementioned software initiatives are driven by the desire to discover impactful biology. Our laboratory also leverages large cancer datasets to unravel the intricacies of germline and somatic cancer genetics, often through an epidemiological lens. Using over 8,000 germline exomes from The Cancer Genome Atlas, we have shown that age at cancer diagnosis is negatively associated with the number of harmful alleles within known cancer risk genes. Along with extramural collaborators, we have explored the breast cancer mutational landscape (exomes and genomes) across more than 1,100 racially and ethnically diverse women. Individuals with African ancestry – particularly Nigerians – were more likely to harbor aggressive molecular features, which is consistent with known clinical differences. Our work continues to utilize germline and somatic DNA sequencing data to enhance understanding of cancer susceptibility, early clonal expansion, and disparities amongst populations.

Lab Members

Selected Publications

  1. Wang, S.*, Pitt, J. J.*, Zheng, Y., Yoshimatsu, T., Gao, G. , Sanni, A., Oluwasola, O., Ajani, M. … Olopade, O. I. Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria. In press (International Journal of Cancer).
  2. Baughman, M., Chard, R., Ward, L., Pitt, J. J., Chard, K., & Foster, I. T. (2018). Profiling and Predicting Application Performance on the Cloud. 2018 IEEE/ACM 11th International Conference on Utility and Cloud Computing (UCC), 21–30.
  3. Pitt, J. J.*, Riester, M.*, Zheng, Y., Yoshimatsu, T. F., Sanni, A., Oluwasola, O., … Barretina, J. (2018). Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features. Nature Communications, 9(1), 4181.
  4. Pitt, J. J., Zheng, Y., & Olopade, O. I. (2018). Genetic Ancestry May Influence the Evolutionary Trajectory of Cancers. Cancer Cell, 34(4), 529–530.
  5. Pitroda, S. P., Khodarev, N. N., Huang, L., Uppal, A., Wightman, S. C., Ganai, S., Joseph, N., Pitt, J. … Weichselbaum, R. R. (2018). Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis. Nature Communications, 9(1), 1793.
  6. Cheng, J., Demeulemeester, J., Wedge, D. C., Vollan, H. K. M., Pitt, J. J., Russnes, H. G., … Van Loo, P. (2017). Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors. Nature Communications, 8(1), 1221.
  7. Huo, D., Hu, H., Rhie, S. K., Gamazon, E. R., Cherniack, A. D., Liu, J., Yoshimatsu, T., Pitt, J.J. … Olopade, O. I. (2017). Comparison of Breast Cancer Molecular Features and Survival by African and European Ancestry in The Cancer Genome Atlas. JAMA Oncol. 3(12), 1654–1662.
  8. Camps, J., Pitt, J. J., Emons, G., Hummon, A. B., Case, C. M., Grade, M., … Ried, T. (2013). Genetic amplification of the NOTCH modulator LNX2 upregulates the WNT/B-catenin pathway in colorectal cancer. Cancer Research73(6), 2003–2013.
  9. Hummon, A. B., Pitt, J. J., Camps, J., Emons, G., Skube, S. B., Huppi, K., … Caplen, N. J. (2012). Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells. Molecular Cancer, 11, 1.
  10. Mackiewicz, M., Huppi, K., Pitt, J. J., Dorsey, T. H., Ambs, S., & Caplen, N. J. (2011). Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNA. Breast Cancer Research and Treatment, 130(2), 663–679.

* Indicates co-first authorship