We are generally interested in the mechanisms that drive the proliferation of cells under physiological and pathological conditions.

Cell proliferation is required during embryonic development, to maintain homeostasis in adult organisms, and in response to injury. In all these cases, cells can be actively proliferating but cell divisions are tightly controlled. We still don’t fully understand how proliferation, survival, and differentiation signals are integrated to ensure proper development. For example, why are the regenerative properties of adult organs and tissues so restricted in mammals (such as mice and humans) that there is limited regeneration in response to injury? We are addressing this question using a variety of approaches in several cellular and organismal models. For example, we are comparing embryonic and adult stem cells in mice and humans to gain a better understanding of the biology of these cell types, including at the epigenetic level. We are also using an evolutionary approach, investigating the regenerative potential of the flatworm Schmidtea mediterranea. Finally, we are developing genetic tools in mice to explore the cellular and molecular mechanisms of tissue repair.

The accumulation of genetic and epigenetic alterations transforms normal cells into cancer cells characterized by uncontrolled proliferation. But how does cancer initiate and progress? In the hierarchy from stem cells to terminally differentiated cells, what cell types have the potential to act as target cells for cancer? And how do mutant cells gain the ability to propagate tumors in the long term? At the molecular levels, can we identify and validate novel candidate targets to inhibit cancer development? To address these questions, we study the mechanisms of central cancer pathways of Ras, Myc, p53, and RB during the tumorigenic process. We aim to develop “precision medicine” approaches in some of the most lethal human cancers. To this end, we leverage publicly-available cancer genomics data and generate our own set of genome-wide genetic and epigenetic data sets (e.g. RNA-seq, ChIP-seq, ATAC-seq, CRISPR/Cas9 screens) to identify novel regulators of cancer growth. We also develop novel genetic approaches in mice to conclusively determine the function of these candidate genes and pathways in tumorigenesis in vivo. Finally, we team up with pharmaceutical companies and clinicians in academic centers to translate our discoveries into the clinic as rapidly as possible.

Embryonic and Adult Stem Cells, Regeneration
Focus: quiescence, self-renewal, cell plasticity, RB pathway, mice, planarians

Lung Cancer
Focus: SCLC, metastasis, cell-of-origin, cellular heterogeneity, response to radiation and chemo-therapy, functional genomics, immunotherapies

Gastrointestinal Cancers
Focus: pediatrics HCC, fibrolamellar carcinoma, pancreatic cancer, proteomics, kinases/phosphatases/methyltransferases