Alexandre Gaspar Maia, Ph.D., leads Mayo Clinic's Functional Epigenomics Laboratory, where he combines advanced sequencing techniques to profile the epigenomic landscape at a single-cell level, mostly focusing on enhancer elements, or enhancers.
Dr. Maia has worked extensively in epigenetic regulation of stem cells, cellular reprogramming and cancer, and is now particularly interested in using epigenomic profiling of enhancer elements to identify biomarkers of sensitivity to poly (ADP ribose) polymerase (PARP)-inhibitors in the context of ovarian and breast cancers.
Dr. Maia's long-term goal is to understand how enhancers drive resistance to drug treatment in cancer and to dissect the mechanisms by which those enhancers are activated and silenced during cancer transformation.
- Discovery of tumor-specific enhancers in circulating tumor cells associated with chemotherapy resistance in ovarian cancer. The potential of capturing rare populations of circulating tumor cells (CTCs) from the blood of patients has been very appealing, as it gives a single-cell resolution analysis of the metastatic status before and after treatment from a minimally invasive liquid biopsy. Researchers in the Functional Epigenomics Lab aim to identify tumor-specific enhancers in rare populations of CTCs in patients with ovarian cancer, before and after chemotherapy, and determine whether such enhancers can be used as a biomarker for cancer resistance, even prior to changes in expression.
- Discovery of tumor-specific enhancers as novel biomarkers associated with PARP-inhibitor resistance in triple negative breast cancer (TNBC). The lab aims to identify novel biomarkers of PARP-inhibitor resistance, utilizing a broad range of some of the most advanced techniques in epigenomic profiling, CRISPR-based screens, CTC isolation, 3-D organoid cultures and patient-derived xenograft models, in collaboration with other labs at Mayo Clinic. This will benefit the 40 percent of patients with TNBC who can respond to PARP-inhibitor treatment.
- Mechanisms of enhancer silencing and reactivation in cancer progression. The role of enhancers in malignant transformation has been highlighted by the discovery of tumor-specific enhancers. Dr. Maia and colleagues in the Functional Epigenomics Lab aim to unravel the mechanisms by which enhancers are activated in tumor cells.
Significance to patient care
The identification of biomarkers for drug resistance to determine which patients will be responsive to which treatments will be a great step forward in cancer treatment. Dr. Maia aims to develop the technology to detect such biomarkers using liquid biopsy, which will greatly increase applications in the clinical setting. This is ultimately the goal of personalized medicine.
- Recipient, C1 Award for the Single-Cell Auto Prep System with ATAC-seq, Fluidigm, 2016
- Postdoctoral Fellowship, New York Stem Cell Foundation, 2014-2017
- Recipient, Postdoctoral Recognition Award, Icahn School of Medicine at Mount Sinai, 2014
- Postdoctoral Fellowship, Breast Cancer Research Program, Department of Defense, 2011-2014
- Ph.D. Fellowship, Foundation for Science and Technology, Portugal, 2003-2007