Paul Cairns, PhD
- Postdoctoral Fellowship with Dr. David Sidransky, Johns Hopkins Hospital, Baltimore
- PhD, Clinical Cancer Genetics, University of Birmingham, UK
- Epigenomics for the Stratification of the Aggressive Potential of Small Renal Masses and RCC.
- Ultra-Deep Sequencing of p53 Mutation in Blood for Early Detection of Curable Ovarian Cancer.
- Characterization and Biology of a Novel Molecular Subgroup of HGS Ovarian Cancer.
- Methylation and Sequence Mutation for Prediction of Risk of Breast Cancer in Women with Benign Disease or DCIS.
- Identification of an Epigenetic Signature for Progression in Superficial Urothelial Cancer.
The field of epigenetics addresses the set of stable changes that influence gene expression patterns that do not arise from primary mutations in gene sequence. The primary focus of our research program is the translation of basic knowledge of the epigenetics of cancer to improve the early detection, prognosis, and prediction of response to treatment of cancer through novel and well-conceived molecular tests.
Cancer is a disease initiated and driven by the accumulation of genetic and epigenetic alterations of key genes acquired over a lifetime. These alterations can be used as targets for the detection of tumor cells in clinical specimens such as needle biopsies, or body fluids such as blood or urine i.e. liquid biopsies. A molecular test that targets gene alterations at the DNA level has several conceptual advantages for the successful early detection of cancer. The alteration may be present, and therefore potentially detectable, before the cancer can be found by imaging or traditional pathology. This is because either the alteration precedes overt cancer growth, or the abnormal cells represent a tiny fraction of the cell population in the biopsy. We pioneered methylation-based early detection of prostate, kidney and bladder cancer in urine, as well as ovarian and breast cancer in blood, and we are at the forefront of developing metrics for the more rapid and robust validation of molecular tests.
It is well known that patients with the same type and stage of cancer can have different outcomes. We are developing an aggressiveness index to predict how likely it is that a tumor will recur and progress or not, based on the epigenetic heterogeneity that underlies the different behavior of each person’s tumor. The ultimate goal is to simultaneously detect a cancer at an early curable stage, and to predict the best management based on the potential of the cancer to progress.
As we uncover the genes that are altered in cancer, we are investigating if epigenetic silencing of genes with a strong biological rationale can be used to predict a better or worse response to particular therapies. At present, we cannot predict whom a specific type of chemotherapy will work for. If we could identify, ahead of time, the people who will show a poor response, oncologists could give additional or different treatment. Epigenetic alterations are potentially reversible by treatment with certain drugs; hence, it may be possible to restore the sensitivity of a tumor to a standard chemotherapy.
Ibanez, I.,Dulaimi, E., Hoffman, A.M., Al-Saleem, T., Uzzo, R.G. and Cairns, P. Identification of Novel Target Genes by an Epigenetic Reactivation Screen of Kidney Cancer. Cancer Research 66:5021-8, 2006. PubMed PMID: 16707423. PubMed
Kagan, J, Srivastava, S., Belinsky, SA and Cairns, P. Towards Clinical Application of Methylated DNA Sequences as Cancer Biomarkers: a Joint NCI EDRN & NIST Workshop on Standards, Methods, Assays, Reagents and Tools (SMART). Cancer Research 67:4545-9, 2007. PubMed
Cairns, P. Gene Methylation and Early Detection of Genitourinary Cancer – the road ahead. Nature Reviews Cancer 7:531-43, 2007 PubMed PMID: 17585333. PubMed
Potapova, A., Hoffman, AH, Godwin, AK, Al-Saleem, T. and Cairns, P. Promoter Hypermethylation of the PALB2 Susceptibility Gene in Inherited and Sporadic Breast and Ovarian Cancer. Cancer Research 68: 998-1002, 2008. PubMed
Brooks JD, Cairns P, Shore RE, Klein CB, Wirgin I, Afanasyeva Y, Zeleniuch-Jacquotte A. DNA methylation in pre-diagnostic serum samples of breast cancer cases: Results of a nested case-control study. Cancer Epidemiol. 34:717-23, 2010. PubMed
I. Ibragimova, Inmaculada Ibáñez de Cáceres, Amanda M. Hoffman, Anna Potapova, Essel Dulaimi, Tahseen Al-Saleem, Gary R. Hudes, Michael F. Ochs and Paul Cairns. Global Reactivation of Epigenetically Silenced Genes in Prostate Cancer. Cancer Prevention Research 3:1084-92, 2010 PubMed Central PMCID: PMC2933318. PubMed
Hoffman, A. and Cairns, P. The Epigenetics of Kidney and Bladder Cancer. Epigenomics 3: 19-34, 2011. PubMed
Ibragimova, I., Maradeo, M.E., Dulaimi, E., Cairns, P. Aberrant promoter hypermethylation of PBRM1, BAP1, SETD2, KDM6A and other chromatin-modifying genes is absent or rare in clear cell RCC. Epigenetics 8:486-493, 2013. PubMed
Ibragimova, I., Slifker, M.J., Maradeo, M.E., Banumathy, G., Dulaimi, E., Uzzo, R.G., Cairns, P. Genome-wide promoter methylome of small renal masses. PLoS One 8:e77309, 2013. PubMed Central PMCID: PMC3811999. PubMed
Gowrishankar, B., Ibragimova, I., Zhou, Y., Slifker MJ, Devarajan K., Al-Saleem, T., Uzzo, R.G., Cairns, P. MicroRNA expression signatures of stage, grade, and progression in clear cell RCC. Cancer Biology and Therapy 15:329-341, 2014. PubMed
Ibragimova, I., Dulaimi, E., Slifker, M.J., Chen, D.Y., Uzzo, R.G., Cairns, P. A global profile of gene promoter methylation in treatment-naïve urothelial cancer. Epigenetics 9: 760-73, 2014. PubMed Central PMCID: PMC4063835. PubMed