Markus Schober, PhD

Assistant Professor; Departments of Dermatology (Fac) and Cell Biology

RESEARCH THEMES:
Cell Biology, Dermatology

KEYWORDS:
Cancer heterogeneity, Cancer Stem Cells, Cell Migration, Morphogenesis, Self-renewal, Signal Transduction, Stem Cell Biology Gene Expression

 

 

 

Contact Information

522 First Avenue
Smilow Research Center
Floor 4, Room 411
New York, NY 10016

Tel: 212-263-9251
Email: markus.schober@nyumc.org

Defining Cancer Stem Cell Self-Renewal and Phenotypic Heterogeneity

Self-renewal is a vital process that enables normal stem cells to maintain their own identity and proliferative potential throughout life while their highly specialized descendants replenish damaged cells and heal wounded tissue after injury. Likewise, self-renewal also allows cancer stem cells to sustain unlimited tumor growth. Whether self-renewal in normal stem cells and cancer stem cells is regulated by the same or rather distinct molecular mechanisms is a pivotal question in stem and cancer cell biology, because effective therapies should only target cancer stem cells while leaving normal stem cells unaffected. Still, most cancer treatments available today hit rapidly proliferating and dividing cells. Such therapies not only cause severe side effects on normal tissues, they also allow some cancer stem cells to escape treatment to initiate recurrent tumors after therapy.

Using skin and cutaneous squamous cell carcinoma as a model, we begin to uncover the identity and self-renewal program of cancer stem cells in comparison to normal tissue stem cells. Our current research focuses on two critical questions:

  1. How do cancer stem cells self-renew? We identified a small group of genes that are essential for cancer stem cell self-renewal and dispensable for normal skin epithelial stem cell functions in mouse and human. We hypothesize that these molecules may serve as cancer stem cell specific master regulators that define their identity and govern their self-renewing potential. Our research aims to uncover the molecular circuitry that controls these master regulators and enables their functions. The identification of these regulatory mechanisms will be a first step towards the definition of cancer stem cell specific diagnostic markers and the development of effective therapies for cancer patients with limited effects on normal tissues.
  2. How can cancer stem cells interconvert between phenotypically distinct states? We and others discovered that cancer stem cells can exist in closely related but phenotypically distinct states. These phenotypic differences allow some cancer stem cells to restist therapy and initiate relapse after remission, while others respond and die. To uncover the cellular and molecular mechanisms that empower cancer stem cells to interconvert between these phenotypically distinctive states, we developed genetically encoded, fluorescent reporter that enable us to track the cells’ behavior and profile their molecular characteristics within tumors.

Once we begin to better understand how a cancer stem cells’ identity, self-renewing potential, and phenotypic behaviors are controlled within intact tumors, we can begin to develop regimens that eradicate tumors while leaving normal tissues unaffected.