The Charlotte Kuperwasser Lab

Research Publications Cell Biology Genetics

 

Dr. Kuperwasser leads the Raymond and Beverly Sackler Convergence Lab.  weblink

The Kuperwasser Laboratory focuses on understanding the various aspects of normal and carcinogenic breast development, with the emphasis on molecular mechanisms that regulate normal and cancer stem cells, differentiation, and stromal-epithelial interactions involved during progression and metastasis. The laboratory has several major areas of focus.

Genomic & Chemical Library Screening

Recent work from the Kuperwasser group has shown that the differentiation state of the cell-of-origin determines the type of cancer will eventually form. Other recent findings have also provided strong molecular evidence supporting the concept that haploinsufficiency for genes in may be associated with features of malignancy. Using these insights, the Kuperwasser group is employing various genomic, proteomic and chemical platforms developed by various members of the Raymond and Beverly Sackler Convergence Lab to study the following: 

We are interested in:

  • Identifying novel breast cancer drivers
  • Identifying novel drivers of metastasis
  • Identifying networks that control cell fate decision and differentiation
  • Determining how the differentiation state of the cell of origin determines the genetic landscape of a cancer

Kuperwasser Fig 1

Figure 1. Single cell clones generated from human breast stem/progenitor cells

Cellular Plasticity & Organogenesis

A major effort in the Kuperwasser lab is to define the cellular precursors to human breast cancers and uncover how mutations or stable epigenetic changes sustained in these cells affect cell fate decisions and cellular plasticity to create heterogeneous tumor phenotypes. Efforts have been focused on uncovering the transcriptional mediators for somatic cell plasticity including transcription factors, chromatin modifiers as well as factors that post-translationally modify these factors (eg. SLUG/SNAI2, TAZ/WWTR1,TBX3 etc). This work has revealed fundamental mechanisms that regulate normal and cancer stem-like states as well as how these factors might be exploited to contribute to metastasis.

Other ongoing interests and projects relating to this area include:

  • Identifying breast tissue hierarchy, stem cells, and factors that control cellular plasticity and tissue development
  • Understanding how mutations reprogram cell identity
  • Understanding the effects of aging on stem cell fitness
  • Reconstructing human breast tissues in vivo

Kuperwasser Fig 2 

Figure 2. Genetically labeled mouse mammary gland tissue

Stroma in Development & Disease

The. Kuperwasser group is working towards identifying and understanding how normal breast stem cells, as well as breast cancer stem cells interact with the host cells during cancer formation, expansion and metastasis. Currently the lab is defining how stromal rigidity due to fibroblast activation affects the recruitment and stimulation of immune cells, which likely participate in cancer development and progression. In addition, the lab is examining how adipocytes in the obese state participate as tumor promoters or suppressors. For these studies they have developed and are utilizing various novel human breast xenograft model systems as well as complementary in vitro co-cultures and 3D culture systems to identify molecular pathways that mediate the complex interactions during the various aspects of normal and neoplastic breast development.

Additional interests and projects are:

  • Understanding the role of adipose stromal cells in cancer initiation
  • Defining how changes in mechanotransduction affect development and disease
  • Eludicadating the molecular mechanisms of microcalcification formation in disease
  • Defining the role of stromal cells in the development of cancer in high risk high risk patients

Kuperwasser Fig 3 

Figure 3. Mouse mammary fat tissue (adipocytes in red, blood vessels in green) in lean vs obese mice

Learn more about the Kuperwasser lab spotlight

Apply to the Sackler School

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The priority application deadlines are as follows:

December 1: Basic Science Division PhD Programs

February 15: Building Diversity in Biomedical Sciences

March 31: Post-Baccalaureate Research Program

May 1: Clinical & Translational Science, MS in Pharmacology & Drug Development

June 15: Online Certificate in Fundamentals of Clinical Care Research