Markus Schober, PhD

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Assistant Professor of Dermatology
Ph.D., 2003 University of Vienna, Austria

LAB WEBSITE:
Schober Lab
RESEARCH THEMES:
Cancer Stem Cells, Signal Transduction, Cell Migration, Morphogenesis, Stem Cell Biology Gene Expression, self-renewal, cancer heterogeneity
KEYWORDS:
Cancer Stem Cells, Skin Cancer, TGFβ, Integrin, Focal Adhesion Kinase, Sox2

Contact Information

New York University School of Medicine
Smilow Research Center
522 First Avenue 4th floor
New York, NY 10016
Tel: (212) 263-9251
E-mail: 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.

 

Research is supported by the National Institutes of Health

Selected Publications: 

 

  • Schober, M.,and Fuchs, E. (2011). Tumor-initiating stem cells of squamous cell carcinomas and their control by TGFβ and integrin/focal adhesion kinase (FAK) signaling. PNAS. 108 (26) 10544-10549. PMID: 21670270
  • Seidel, K., Ahn, C.P., Lyons,D., Nee, A., Ting, K., Brownell, I., Cao, T., Carano, R.A.D., Curran, T., Schober, M., Fuchs, E.,Joyner, A., Martin, G.R., de Sauvage, F.J., Klein, O.D. (2010) Hedgehog signaling directs generation of progeny from adult stem cells in the continuously-growing mouse incisor. Development. 137(22):3753-61. PMID: 20978073
  • Greco, V., Chen, T., Rendl, M., Schober, M., Pasolli, HA., Stokes, N., Dela Cruz-Racelis, J., and Fuchs, E. (2009). A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell. 4(2):155-69. PMID: 19200804
  • Guasch, G., Schober, M.,  Pasolli, H.A.,  Belmont Conn, E., Polak, L. and Fuchs, E.(2007). Loss of TGFβ Signaling Destabilizes Homeostasis and Promotes Squamous Cell Carcinomas in Stratified Epithelia. Cancer Cell 12 (4). PMID: 17936557