Dominic Smiraglia


Research Interests:

DNA methylation and epigenetics in cancer and normal cells Epigenetic regulation of androgen receptor signaling Role of polyamine metabolism in prostate cancer genomic and epigenomic stability Epigenetic dysregulation as a source of lineage plasticity in prostate cancer

About Dominic Smiraglia


Dominic J. Smiraglia, PhD, joined the Roswell Park Comprehensive Cancer Center faculty in 2003 as an Assistant Member in the Department of Cancer Genetics, and is currently an Associate Member in the Department of Cell Stress Biology.

Dr. Smiraglia comes to Roswell Park from the Division of Human Cancer Genetics at the Ohio State University (OSU), where he served as a Postdoctoral Fellow and as a Research Scientist. He earned his doctoral degree in the Department of Cell and Molecular Biology in 1997 from Roswell Park's Graduate Division and completed postdoctoral training in the Department of Molecular Virology, Immunology and Medical Genetics at OSU.

Dr. Smiraglia is a member of The DNA Methylation Society, The American Association for Cancer Research, and the Society for Basic Urological Research. He has authored or co-authored more than 75 journal publications and book chapters.

View the Smiraglia Lab


Roswell Park Comprehensive Cancer Center
  • Associate Professor of Oncology
  • Associate Member
  • Department of Cell Stress Biology
  • Director of Graduate Studies, Cancer Genomics and Computational Oncology PhD Program


Education and Training:

  • BA - State University of New York at Buffalo
  • 1997 - PhD - Roswell Park Comprehensive Cancer Center, Buffalo, NY


  • The Ohio State University, Department of Molecular Virology, Immunology, and Medical Genetics, Division of Human Cancer Genetics

Professional Memberships:

  • The DNA Methylation Society
  • The American Association for Cancer Research
  • Society for Basic Urological Research

Honors & Awards:

  • 2019 - Roswell Park Cancer Institute, Dean’s Award for Excellence in Graduate Education
  • 2017 - Roswell Park Cancer Institute, Graduate Student Association Award for Faculty Excellence in Mentoring and Teaching


Research Overview:

Smiraglia Lab

My lab has two major themes over-arching my research program. The first is the idea that epigenetic modifications provide an exceptional route for cancer cell ‘evolution’ as cancers progress to advanced phenotypes. The second is the idea that epigenetic regulation is the means by which the genome can be responsive to the environment. These themes overlap in the sense that the environmental challenges to cancer cells change during tumor progression as they are required to adapt to metabolic pressures, such as hypoxia, and stress on nucleotide pools. Further challenges come with changes in cell-cell interactions as cells leave their normal stromal interactions and metastasize. In the case of a hormone responsive tumor like prostate cancer, the environmental changes also include changes in hormonal stimulation and nuclear receptor action. Such environmental stresses, or challenges, are key to providing the selective pressures that are required to drive ‘evolution’ of cancers cells, making them adept at progressing to more advanced phenotypes. I have an established track record in molecular genetics with a strong focus on DNA methylation in cancer. Specifically in prostate cancer, I have many years of experience studying epigenetic deregulation in both human and mouse models. Over the last ten years I have expanded these efforts into understanding folate biology, polyamine metabolism, and one-carbon metabolism in prostate cancer and how this influences genome integrity and DNA methylation. Additional efforts are to expand these lines of research towards studies into the effect of dietary folate modulation, as well as pharmacological manipulation, on prostate cancer development and progression to advanced phenotypes in transgenic mouse models and human xenograft models. These efforts intersect with our studies into how epigenetic reprogramming of enhancers contributes to lineage plasticity as a means of escape from the control of androgen deprivation therapy, as folate and polyamine metabolism significantly impact acetyl- and methyl- donor pools required to for epigenetic regulation of the genome.

Over the last ten years my research trajectory has been leading to combining our research into basic epigenetic mechanisms with our studies on metabolism and development of novel therapeutic strategies leveraging metabolism. Recent studies into pharmacological manipulation of polyamine catabolism and the methionine salvage pathway have explored novel therapeutic strategies to treat advanced stages of prostate cancer. Concurrently, we have been studying the role of epigenetic dysregulation in the development of advanced stage prostate cancer. Thus, my lab is uniquely positioned to extend our past work by exploring how metabolic adaptation to drug induced stress can be propagated to the epigenome. We aim to provide key mechanistic insight into the intersection between two fundamental processes driving tumorigenesis; metabolic adaptation and epigenomic reprogramming. This will provide novel insights into how to leverage the metabolic effects on the epigenome for better epigenetic therapy.


Full Publications list on PubMed

Long MD*, Jacobi JJ*, Singh PK, Llimos G, Wani SA, Rowsam AM, Rosario SR, Hoogstraat M, Linder S, Kirk J, Affronti HC, Bergman A, Zwart W, Campbell MJ, Smiraglia DJ. Reduced NCOR2 expression accelerates androgen deprivation therapy failure in prostate cancer. Cell Reports 37, 110109 *These authors contributed equally to this work.

Affronti HC*, Rowsam AM*, Pellerite AJ, Rosario SR, Long MD, Jacobi JJ, Bianchi-Smiraglia A, Boerlin CS, Gillard BM, Karasik E, Foster BA, Moser M, Wilton JH, Attwood K, Nikiforov MA, Azabdaftari G, Pili R, Phillips JG, Casero RA Jr, Smiraglia DJ. Pharmacological polyamine catabolism upregulation with methionine salvage pathway inhibition as an effective prostate cancer therapy. Nat Commun. 2020 Jan 7;11(1):52. doi: 10.1038/s41467-019-13950-4. PMCID:PMC6946658. *These authors contributed equally to this work.

Rosario SR, Long MD, Affronti HC, Rowsam AM, Eng KH, Smiraglia DJ. (2018) Pan-cancer analysis of transcriptional metabolic dysregulation using The Cancer Genome Atlas. Nature Communications 018 Dec 14;9(1):5330. doi: 10.1038/s41467-018-07232-8. PMCID: PMC6294258

Long MD, Dhiman VK, Affronti HC, Hu Q, Liu S, Smiraglia DJ. Dynamic patterns of DNA methylation in the normal prostate epithelial differentiation program are targets of aberrant methylation in prostate cancer. Sci Rep 11, 11405 (2021).

Rosario SR, Jacobi JJ, Long MD, Affronti HC, Rowsam AM, Smiraglia DJ. JAZF1: A Master Metabolic Regulator of Sensitivity to a Polyamine Targeted Therapy. Mol Cancer Res. 2023 Jan 3;21(1):24-35. doi: 10.1158/1541-7786.MCR-22-0316. PMID: 36166196.