Professional Education


  • Doctor of Philosophy, Wayne State University (2015)
  • Master of Science, Universita Degli Studi Di Pisa (2006)

Stanford Advisors


All Publications


  • Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell Cheung, P., Vallania, F., Warsinske, H. C., Donato, M., Schaffert, S., Chang, S. E., Dvorak, M., Dekker, C. L., Davis, M. M., Utz, P. J., Khatri, P., Kuo, A. J. 2018

    Abstract

    Post-translational modifications of histone proteins and exchanges of histone variants of chromatin are central to the regulation of nearly all DNA-templated biological processes. However, the degree and variability of chromatin modifications in specific human immune cells remain largely unknown. Here, we employ a highly multiplexed mass cytometry analysis to profile the global levels of a broad array of chromatin modifications in primary human immune cells at the single-cell level. Our data reveal markedly different cell-type- and hematopoietic-lineage-specific chromatin modification patterns. Differential analysis between younger and older adults shows that aging is associated with increased heterogeneity between individuals and elevated cell-to-cell variability in chromatin modifications. Analysis of a twin cohort unveils heritability of chromatin modifications and demonstrates that aging-related chromatin alterations are predominantly driven by non-heritable influences. Together, we present a powerful platform for chromatin and immunology research. Our discoveries highlight the profound impacts of aging on chromatin modifications.

    View details for DOI 10.1016/j.cell.2018.03.079

    View details for PubMedID 29706550

  • Inflammatory macrophage-associated 3-gene signature predicts subclinical allograft injury and graft survival. JCI insight Azad, T. D., Donato, M., Heylen, L., Liu, A. B., Shen-Orr, S. S., Sweeney, T. E., Maltzman, J. S., Naesens, M., Khatri, P. 2018; 3 (2)

    Abstract

    Late allograft failure is characterized by cumulative subclinical insults manifesting over many years. Although immunomodulatory therapies targeting host T cells have improved short-term survival rates, rates of chronic allograft loss remain high. We hypothesized that other immune cell types may drive subclinical injury, ultimately leading to graft failure. We collected whole-genome transcriptome profiles from 15 independent cohorts composed of 1,697 biopsy samples to assess the association of an inflammatory macrophage polarization-specific gene signature with subclinical injury. We applied penalized regression to a subset of the data sets and identified a 3-gene inflammatory macrophage-derived signature. We validated discriminatory power of the 3-gene signature in 3 independent renal transplant data sets with mean AUC of 0.91. In a longitudinal cohort, the 3-gene signature strongly correlated with extent of injury and accurately predicted progression of subclinical injury 18 months before clinical manifestation. The 3-gene signature also stratified patients at high risk of graft failure as soon as 15 days after biopsy. We found that the 3-gene signature also distinguished acute rejection (AR) accurately in 3 heart transplant data sets but not in lung transplant. Overall, we identified a parsimonious signature capable of diagnosing AR, recognizing subclinical injury, and risk-stratifying renal transplant patients. Our results strongly suggest that inflammatory macrophages may be a viable therapeutic target to improve long-term outcomes for organ transplantation patients.

    View details for DOI 10.1172/jci.insight.95659

    View details for PubMedID 29367465