Notch signaling

NOTCH1 Plasticity & Epidermal Disease Lab

NOTCH1 Plasticity & Epidermal Disease Lab

RESEARCH

Our laboratory focuses on understanding how alterations in calcium homeostasis, cell-cycle regulation, and stress response pathways affect epidermal physiology and carcinogenesis. We aim to uncover the molecular mechanisms underlying impaired cell adhesion, differentiation, and DNA damage response in skin pathologies and cancer, with the goal of identifying novel therapeutic strategies.

Main topics of our lab include:

1) Molecular mechanisms of Hailey-Hailey Disease (HHD)

MNC - Molecular Networks in Cancer Unit

MNC - Molecular Networks in Cancer Unit

Alterations in Notch signaling play a crucial role in cancer development and progression. Depending on the cancer context, Notch signaling can act as either an oncogene or a tumor suppressor. Understanding the mechanisms underlying this dual role is essential for identifying novel molecular targets and developing innovative therapeutic strategies.

NOTCH1 is aberrantly activated in chronic lymphocytic leukemia hematopoietic stem cells

To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38-HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38-and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors.

Histone Modifications Drive Aberrant Notch3 Expression/Activity and Growth in T-ALL

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer caused by the deregulation of key T-cell developmental pathways, including Notch signaling. Aberrant Notch signaling in T-ALL occurs by NOTCH1 gain-of-function mutations and by NOTCH3 overexpression. Although NOTCH3 is assumed as a Notch1 target, machinery driving its transcription in T-ALL is undefined in leukemia subsets lacking Notchl activation.

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