Maria Isabel Dominguez PhD

Biography

My laboratory focuses on the role of Wnt/ß-catenin signaling components post-fertilization and in organ development, and how their deregulation leads to diseases such as cancer and congenital diseases. We have made important contributions to this field, identifying novel mechanisms of action for the Ser/Thr kinases CK2 and GSK3ß in Wnt/ß-catenin signaling and embryo development, some of which are now included in developmental biology textbooks (and even in fiction novels/movies). Our innovative work on the transcript expression of CK2 genes in cancer created a paradigm shift in the field and opened new avenues of research (“Mining CK2 in Cancer” was on the top 10% most cited articles by 2017). Recently, we are pioneering the use of the Xenopus laevis model system to the study of rare neurodevelopmental diseases. Our research has been funded from federal and non-federal agencies, disseminated in peer-reviewed publications, and widely reproduced by other researchers. We use complementary experimental and computational approaches, and models such as frogs and mice, cell culture and in vitro assays. We integrate biological and clinical data to understand the mechanisms of disease progression which can be used to develop appropriate therapeutic approaches. My laboratory has 3 research interests:


1. Define the molecular and biological mechanisms underlying rare human neurodevelopmental disorders syndromes Okur-Chung Neurodevelopmental Syndrome (OCNDS, OMIM #617062) and Poirier-Bienvenu Neurodevelopmental Syndrome (POBINDS, OMIM # 618732), characterized by intellectual disability/autism and epilepsy, respectively. OCNDS and POBINDS are attributed to de novo (germline non-inherited) variants in the genes CSNK2A1 and CSNK2B, respectively; genes that code for subunits of a kinase that we are experts on, CK2.

2. dentifying the molecular mechanisms controlling the activation of Wnt/ß-catenin signaling, which are still elusive despite the fact that Wnt/ß-catenin signaling deregulation causes several human diseases (e.g. cancer and congenital disease). Our aim is to understand of the molecular events leading to ß-catenin activation, which will help develop novel and specific inhibitors for the treatment of cancers with upregulated nuclear ß-catenin levels.

3. Defining the alterations of CK2 genes in tumor types. CK2 has been proposed for a number of years as a therapeutic target for cancer, as it was found to be upregulated in a small subset of patient tumor samples. Indeed, there are clinical trials in place to test CK2 inhibitors. However, we do not have a whole picture of the expression of CK2 genes in cancer that can direct therapeutic approaches, in particular studies that take advantage of large patient databases are missing.

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