Sean Hackett Large-Scale Statistics of Genomics and Sports

Research

Systems Genetics of Metabolism

My research focuses on understanding how genetic and environmental changes alter the complicated systems of metabolism and physiology. I try to model systems using data-driven approaches that break network-level behavior into simpler sub-questions.

I am currently a postdoc with John Storey where I am working on machine learning oriented approaches to systems genetics and sports analytics.

A summary of my education and research can be found on my curriculum vitae


Graduate Research at Princeton

I recently completed my PhD in the program of Quantitative and Computational Biology (QCB) at Princeton University; my adviser was Josh Rabinowitz.

My research primarily focused on:

  • Integrating multiple types of high-throughput metabolic data (proteins, metabolites and fluxes) using biochemically motivated non-linear reaction equations. Through model comparison of these reaction equations, I was able to predict allosteric regulation. Subsequent experimental work verified three instances of novel regulation of major enzymes.
  • Identifying reoccuring metabolic changes in primary human tumors by statistical analysis of metabolomics data.
  • Understanding how protein levels are determined quantitatively through regulation at the transcriptional and post-transcriptional level.
  • Developing statistical methods for integrating mass spectrometry-based measurements from multiple peptides into protein-level summaries

Published papers from this work are:

  • Sean R. Hackett, Vito R.T. Zanotelli, Wenxin Xu, Jonathan Goya, Junyoung O. Park, David H. Perlman, Patrick A. Gibney, David Botstein, John D. Storey, and Joshua D. Rabinowitz. Systems-level analysis of mechansims controlling yeast metabolic flux. Science, 345, 2016.
  • Jurre Kamphorst, Michel Nofal, Cosimo Commisso, Sean R. Hackett, Wenyun Lu, Elda Grabocka, George Miller, Jeffrey Drebin, Matthew Vander Heiden, Dafna Bar-Sagi, Craig Thompson, Josh Rabinowitz. Human pancreatic cancer tumors are nutrient poor and the tumor cells actively scavenge extracellular protein. Cancer Research, 75, 2015.
  • Robin Mathew, Sinan Khor, Sean R. Hackett, Joshua D. Rabinowitz, David H. Perlman, and Eileen White. Functional Role of Autophagy-Mediated Proteome Remodeling in Cell Survival Signaling and Innate Immunity. Molecular Cell, 55(6), 2014.
  • Jeffrey S. Breunig, Sean R. Hackett, Joshua D. Rabinowitz, Leonid Kruglyak. Genetic Basis of Metabolome Variation in Yeast. PLoS Genetics, 10(4) e1004142, 2014.
  • Cosimo Commisso, Shawn M Davidson, Rengin G Soydaner-Azeloglu, Seth J Parker, Jurre J Kamphorst, Sean Hackett, Elda Grabocka, Michel Nofal, Jeffrey A Drebin, Craig B Thompson, Joshua D Rabinowitz, Christian M Metallo, Matthew G Vander Heiden, and Dafna Bar-Sagi. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature, 2013.

Undergraduate and post-baccalaureate research at Cornell

After graduating from Cornell, I worked as a research specialist in the laboratory of Andy Clark for four years. During that time I worked on a quantitative/population genetics project aimed to determine how heterogeneous metabolic phenotypes were inter-related and dependent on expression and genetic variation using D. melanogaster as a model.

While this project is still ongoing, several papers have been published:

  • Jennifer K. Grenier, J. Roman Arguello, Margarida Cardoso Moreira, Srikanth Gottipati, Jaaved Mohammed, Sean R. Hackett, Rachel Boughton, Anthony J. Greenberg, and Andrew G. Clark. Global Diversity Lines - A five-continent reference panel of sequenced Drosophila melanogaster strains. G3, 5(4), 2015.
  • Anthony J Greenberg, Sean R. Hackett, Lawrence G Harshman, and Andrew G Clark. Environmental and genetic perturbations reveal different networks of metabolic regulation. Molecular Systems Biology, 7:563, 2011.
  • Anthony J Greenberg, Sean R. Hackett, Lawrence G Harshman, and Andrew G Clark. A Hierarchical Bayesian Model for a Novel Sparse Partial Diallel Crossing Design. Genetics, 185(1):361373, June 2010.

During my undergraduate research with Teresa Gunn at Cornell I investigated the genetic basis of cardiac arrhythmias in dogs:

  • S R Hackett, S W Jung, E Kirkness, J Cruickshank, K L Vikstrom, N S Moise, and T M Gunn. Identification and characterization of canine microsatellite markers in cardiac genes. Animal Genetics, 38(1):8991, February 2007.
  • W Liu, S R Hackett, J Cruickshank, K L Vikstrom, N S Moise, and T M Gunn. Canine microsatellites associated with genes implicated in cardiac development and function. Animal Genetics, 37(1):8788, February 2006.